Volume 192 Issue 4

Quality Use of Medicines indicators can be used to drive system improvements in health care Use of clinical indicators with collection and monitoring of meaningful data has been recognised as important for driving improvements in the safety and quality of health care.1 Quality Use of Medicines (QUM) is one aspect of health care in which continual improvement is vitally important. QUM forms part of Australia’s National Medicines Policy and involves judicious selection of treatment options (including choice between drug or non-drug treatment and no treatment), appropriate choice of medicines when they are required, and safe and efficacious use of medicines.2 Problems with medicines use are costly and occur commonly at all stages of the medicines management pathway3 and in all health care settings. Elderly, paediatric and chronically ill patients are at particular risk of experiencing adverse drug events. In Australia, some 190 000 admissions per year are associated with medicine-related problems, costing the health care system about $660 million, and adverse events involving medicines are consistently among the most frequently reported incidents in voluntary incident-reporting systems.4 Thus, to stimulate quality improvement in this area of health care, it is critical to systematically collect meaningful data about medicines use. Organisations such as the Australian Commission on Safety and Quality in Health Care, the Australian Council on Healthcare Standards (ACHS), the Australian Institute of Health and Welfare, the Council of Australian Governments and the National Prescribing Service are developing clinical indicators for measuring and improving the safety and quality of health care. However, QUM issues are addressed inconsistently in indicators relating to hospitalised patients — probably because medicines management is complex and multidisciplinary3 and not wholly “owned” by any one profession, specialty or discipline. Accordingly, the New South Wales Therapeutic Advisory Group, in collaboration with the Clinical Excellence Commission, has developed Indicators for quality use of medicines in Australian hospitals (QUM indicators).5 The QUM indicators address 30 aspects of care in six areas of practice (Box), including high-risk or high-use medicines (eg, anticoagulants and antibiotics); high-risk populations (eg, paediatric patients); and high-risk clinical settings (eg, transfer from hospital to home or to another health care setting). Many indicators are released for routine use without prior testing or validation in clinical environments, despite the recognised importance of this step.6 We undertook a rigorous development process that included systematic and structured decision making for selecting indicators; consultation with a broad range of clinicians and stakeholders; and pilot-testing in a wide variety of hospitals across Australia. Consequently, each QUM indicator meets the properties of an ideal indicator, such as content validity, face validity, clarity, comparability, measurability, remediability and usefulness.6-8 As we excluded indicators not meeting these criteria, not every area of QUM is addressed. However, our development process has ensured that all the indicators are accepted by clinicians as valid, measurable, important and useful for informing local improvements in QUM. This is likely to enhance their uptake in routine practice. The QUM indicators are primarily designed as tools to inform quality improvement initiatives at the unit, department, or organisation level. They are process measures and provide information about the way medicines management is delivered. Improved performance in the aspects of care measured by process indicators is expected to result in improved health outcomes, as has been demonstrated by Peterson and colleagues.9 The QUM indicator manual (available at http://www.ciap.health. nsw.gov.au/nswtag/indicators.html) describes how to use the indicators to drive improvements in practice and contains detailed instructions for data collection. Using an effective improvement method (eg, drug use evaluation or clinical practice improvement)10,11 and supporting clinicians with appropriate resources and expertise can promote the use of indicators and lead to improvements over time.11 To date, implementing the QUM indicators has included incorporation of selected indicators into programs such as the Electronic Medical Record State Base Build developed by NSW Health; the ACHS Clinical Indicators program, the evaluation of the paediatric National Inpatient Medication Chart, and the National Prescribing Service national drug use evaluation program. The indicators will evolve as their use continues. Adjustments may be needed for a number of reasons, such as clinician feedback and experience; changes in evidence and clinical practice; and alignment with other programs. For example, minor adjustments have been made to the indicators incorporated by the National Prescribing Service and the ACHS in their programs. However, changes should not be introduced without sound reasons and supporting evidence. These indicators are not designed for making comparisons between institutions (benchmarking) or for accountability purposes. If they are to be used for such purposes, further testing of their validity and reliability and appropriate modification is warranted to ensure that comparisons are fair.12 The QUM indicators will be of most use in supporting improvements in health care when data collection and feedback are incorporated into routine clinical practice in all health care settings. To facilitate uptake of the indicators and improvements in care, results must be presented in a time frame and format that is meaningful to clinicians and encourages reflection and discussion.12-15 Clinical teams must be motivated to change their practice and systems in response to results. Using indicators routinely will become easier as electronic medical records and electronic medicines management become more widespread. Appropriate allocation of resources and expertise to support data collection and design and delivery of evidence-based interventions will help.11 We encourage clinicians from all disciplines and specialties to regularly use the QUM indicators relevant to their practice, interpret results in the light of clinical expertise, and drive appropriate system improvements. The effectiveness of these indicators will ultimately be determined by demonstrated improvements in QUM over time at the local and population level. Aspects of care assessed by Quality Use of Medicines indicators5 Antithrombotic therapy Venous thromboembolism risk assessment Venous thromboembolism prophylaxis Enoxaparin dosing Warfarin initiation doses Management of raised international normalised ratio Management of patients with atrial fibrillation Antibiotic therapy Surgical antibiotic prophylaxis Prescribing restricted antibiotics Management of aminoglycoside levels Assessment of community-acquired pneumonia Management of community-acquired pneumonia Medication ordering Medication reconciliation at admission Documentation of adverse drug reactions Use of error-prone abbreviations Prescribing for paediatric patients Prescribing intermittent therapy Prescribing cytotoxic chemotherapy Pain management Assessment of pain intensity Written postoperative pain management plan Continuity of care Discharge management of patients with acute coronary syndrome Discharge management of patients with chronic heart failure Inclusion of medication changes in discharge summary Written information regarding ongoing warfarin management Written information regarding new adverse drug reaction Written asthma action plan New prescriptions for sedatives Hospital-wide medication management policies Potassium storage Clinical pharmacist review Use of pethidine Formulary submissions

Jocelyn S Lowinger BSc(Med), MB BS(Hons), GradCertPublHlth · Helen E Stark BPharm, MBA · Maria Kelly BPharm, DipEd, GradCertBioethics · Clifford F Hughes AO, FRACS, FACC, FACS · Madlen Gazarian MB BS(Hons), MSc(ClinEpi), FRACP · Karen I Kaye BPharm, DipHospPharm, GradCertPharmacoecon

New findings highlight that child sexual abuse is a major risk factor for future illness Child sexual abuse is a social issue but, because of its association with psychological and other problems, it is of special concern to the medical profession.1 An article by Cutajar and colleagues in this issue of the Journal (page 184) shows a greatly increased risk of suicide among people who have experienced sexual abuse in childhood.2 The findings are somewhat stunning: compared with the general population, those with a record of experiencing child sexual abuse had a relative risk of suicide of 18.09 (14.20 for males and 40.38 for females). The relative risk of accidental fatal drug overdose was 88.42 for females and 38.46 for males. Such relative risks are high and of the same order of magnitude as those that link cigarette smoking to lung cancer and chronic obstructive airways disease.3 The study by Cutajar et al, from the School of Psychology, Psychiatry and Psychological Medicine at Monash University, was made possible by the authors’ use of established but underutilised resources, including the Victorian Psychiatric Case Register, the National Coroners Information System, the Victorian Coronial Information Database and records of the Victorian Institute of Forensic Medicine. Although such databases underestimate the prevalence of child sexual abuse and adverse outcomes, they provide a means of extracting data on mental health status and rates of suicide and death from drug overdose for a population in which child sexual abuse had been notified. Increased suicide rates in people who have experienced child sexual abuse are not due to the abuse alone, and suicide is not an inevitable, or even a common, outcome. Just as the great majority of people who smoke cigarettes do not develop cancer of the lung, the great majority of people with a history of child sexual abuse do not commit suicide. Much work needs to be done in examining the intermediary variables in development for victims of child sexual abuse who develop psychological problems in adolescence and young adulthood. Although child sexual abuse is a marker for later psychosocial problems, it may not be the critical formative experience — many patients who become disturbed in adolescence and young adulthood report child sexual abuse but also have a history of other disruptive factors during childhood which centre on such issues as rejection, abandonment, problems regarding trust and an inner sense of chaos often associated with dissociation.1 It is also fascinating that Cutajar et al found that the most common background psychiatric disorder recorded for patients who experienced child sexual abuse and died from self-harm was anxiety rather than depression, which is usually perceived as the background psychopathological experience for those who ultimately commit suicide.4 This needs further research and explication. In clinical practice, it is common to meet women aged in their 50s and 60s who will tell you about a child sexual abuse experience. Despite this, many appear to have led otherwise “normal” lives. Some identify experiences that surround the circumstances of child sexual abuse, such as failure to feel protected, and say that they have always been sensitive about personal safety and trust, lack of order, and unpredictability. On the other hand, psychiatrists see many women during their 30s who have had childhoods that were disorganised and damaging on multiple levels (eg, involving physical and verbal abuse, a pervasive feeling of being unprotected, and chaotic parental relationships) and have included child sexual abuse, and who describe themselves as “complete ratbags in their teens and 20s who got their act together in their early 30s”. None whom I have seen can satisfactorily explain this transformation. One of the findings in the article by Cutajar et al was that the average age at time of suicide for those who experienced child sexual abuse (about 31 years) was similar to the average ages at time of suicide and accidental fatal overdose for the population as a whole. Many doctors and nurses recognise this as the age at which the worst excesses of personality disorder and borderline personality disorder begin to abate. This area of developmental research has been neglected. Patients with borderline personality disorder often report child sexual abuse among myriad insults during childhood development.5,6 These patients often begin to “settle” during their late 20s and late 30s. At my institution, the Emergency Mental Health team has developed modestly successful programs for patients with borderline personality disorder. In general, such programs do not include an extensive or in-depth investigation of the details of child sexual abuse, which many of our patients would be reluctant to discuss but are grateful to have acknowledged. Most of the time is spent discussing their pressing need to feel safe and their feelings of rejection and abandonment. I regularly see patients in a state of crisis and decompensation, apparently because their therapist feels that it is important that the details of their sexual abuse are fully revealed. However, it is not at all convincing that talking through the actual details of the abuse helps. Recently, dialectical behaviour therapy has been shown to be promising for patients with borderline personality disorder.5,7 This therapy does not emphasise revelation of past events related to child sexual abuse as part of the therapeutic exercise. Our understanding of the role and importance of child sexual abuse in disorders of adolescence and early adulthood is incomplete, and our present approach for treating patients with a history of such abuse is therapeutically eclectic. Research is lacking on whether our present approach will reduce the incidence of suicide and fatal overdose among people in their 30s. The moral and cultural complexities of child sexual abuse are appreciated and shared throughout the medical profession, and we are in a good position to provide special leadership. The complex psychopathological conditions that are associated with disorders of adolescence and young adulthood need more investigation, and their association with child sexual abuse needs explanation. The study by Cutajar and colleagues reveals important findings from a study in a complex area. These point to the need for a great deal of work in dissecting issues involved in the pathways to suicide in child sexual abuse victims, including why some patients are vulnerable and others are resilient. Additionally, preventing ongoing child sexual abuse requires improving resources for child protection services and a massive public health response.

Ross S Kalucy FRANZCP, FRACP, FRCPsych

Objective: To determine the rate and risk of suicide and accidental fatal drug overdose (ie, overdose deemed not to have been suicide) in individuals who had been medically ascertained as having been sexually abused during childhood.Design: A historical cohort linkage study of suicide and accidental drug-induced death among victims of child sexual abuse (CSA).Setting and patients: Forensic medical records of 2759 victims of CSA who were assessed between 1964 and 1995 were obtained from the Victorian Institute of Forensic Medicine and linked with coronial data representing a follow-up period of up to 44 years.Main outcome measures: Rates of suicide and accidental fatal drug overdose recorded in coronial databases between 1991 and 2008, and rates of psychiatric disorders and substance use recorded in public mental health databases.Results: Twenty-one cases of fatal self-harm were recorded. Relative risks for suicide and accidental fatal overdose among CSA victims, compared with age-limited national data for the general population, were 18.09 (95% CI, 10.96–29.85; population-attributable risk, 0.37%), and 49.22 (95% CI, 36.11–67.09; population-attributable risk, 0.01%) respectively. Relative risks were higher for female victims. Similar to the general population, CSA victims who died as a result of self-harm were predominantly aged in their 30s at time of death. Most had contact with the public mental health system and half were recorded as being diagnosed with an anxiety disorder.Conclusion: Our data highlight that CSA victims are at increased risk of suicide and accidental fatal drug overdose. CSA is a risk factor that mediates suicide and fatal overdose.

Margaret C Cutajar BA(Hons), DPsych(Clin) · Paul E Mullen MB BS, DSc · James R P Ogloff MA(ClinPsych), JD, PhD · Stuart D Thomas LLM, MSc, PhD · David L Wells MB BS, MA, DMJ · Josie Spataro PhD

Objective: To explore medical students’ views on support services, stigma, and teaching of wellbeing in light of their experiences of stress and distress.Design, participants and setting: Quantitative survey of medical students at five universities in Australia and New Zealand in November 2007.Main outcome measures: Medical students’ experiences of support services, stigma attached to undergoing stress and distress, and teaching of wellbeing.Results: 1328 students completed the survey (26% response rate). Seventy-one per cent of students were aware of support services at their university. Of these, 46% believed the services were adequately promoted, and 49% had either used the services themselves or knew someone who had. Overall, 70% of students had their own general practitioner, but this fell to 45% for international students (P < 0.001). Fifty-five per cent of students believed there was a stigma associated with being a medical student undergoing stress and distress. Fifty-six per cent of students believed they had formal teaching on stress and distress. Students most wanted to learn methods to help somebody else cope and preferred to be taught through formal lectures.Conclusion: Medical curricula on wellbeing should include strategies for self-help and giving assistance to others, and aim to decrease stigma. Adequate and well-promoted support services are required to complement this teaching, in particular for international students.

James M Hillis MB BS(Hons), BMedSci · William R G Perry MB ChB, BSc · Emily Y Carroll MB BS, BHlthSc, DipProfCounselling · Belinda A Hibble MB BS · Marion J Davies MB BS, BMedSci, BPharm · Justin Yousef

Objectives: To assess the impact of two interventions on computer-generated prescriptions for antibiotics — (i) an educational intervention to reduce automatic computerised ordering of repeat antibiotic prescriptions, and (ii) a legislative change prohibiting the “no brand substitution” box being checked as a default setting in prescribing software — and to compare these findings with those of a similar survey we conducted in 2000.Design and setting: Prospective audit of consecutive prescriptions for four antibiotics (amoxycillin, amoxycillin/clavulanate, roxithromycin, and cefaclor) commonly prescribed for upper respiratory tract infections in community pharmacies in New South Wales and Queensland between 1 November 2008 and 31 January 2009.Main outcome measures: Primary outcome: rate of repeat prescription ordering on computer-generated versus handwritten prescriptions. Secondary outcome: rate of checking of the “no brand substitution” box on computer-generated versus handwritten prescriptions.Results: Data were collected on 2807 prescriptions presented to 51 pharmacies (50 in NSW, one in Queensland), of which 2354 were computer-generated. Repeats were ordered on 1633 computer-generated prescriptions (69%) compared with 183 handwritten prescriptions (40%). These proportions were identical to those found in 2000, although the rates of computer prescribing were much higher in this study (84% v 54%). This difference in repeat prescribing was statistically significant (odds ratio adjusted for clustering at pharmacy level, 2.87; 95% CI, 2.32–3.55). Twenty-three (1%) of the computer-generated prescriptions had the “no brand substitution” box checked compared with 3 (0.7%) of the handwritten prescriptions (27% and 1%, respectively, in our previous survey).Conclusions: The legislative change which disallowed having the “no brand substitution” box checked as a default setting in prescribing software had a dramatic impact on the checking of the “no brand substitution” box. In contrast, there was no sustained effect of educating prescribers about software default settings relating to repeat prescribing of antibiotics. Other actions are required if unnecessary repeat prescriptions for some medicines, such as antibiotics, are to be reduced.

David A Newby BPharm, PhD · Jane Robertson BPharm, MMedSci, PhD

Objective: To develop and validate a diabetes risk assessment tool for Australia based on demographic, lifestyle and simple anthropometric measures.Design and setting: 5-year follow-up (2004–2005) of the Australian Diabetes, Obesity and Lifestyle study (AusDiab, 1999–2000).Participants: 6060 AusDiab participants aged 25 years or older who did not have diagnosed diabetes at baseline.Main outcome measures: Incident diabetes at follow-up was defined by treatment with insulin or oral hypoglycaemic agents or by fasting plasma glucose level ≥ 7.0 mmol/L or 2-hour plasma glucose level in an oral glucose tolerance test ≥ 11.1 mmol/L. The risk prediction model was developed using logistic regression and converted to a simple score, which was then validated in two independent Australian cohorts (the Blue Mountains Eye Study and the North West Adelaide Health Study) using the area under the receiver operating characteristic curve (AROC) and the Hosmer–Lemeshow (HL) χ2 statistic.Results: 362 people developed diabetes. Age, sex, ethnicity, parental history of diabetes, history of high blood glucose level, use of antihypertensive medications, smoking, physical inactivity and waist circumference were included in the final prediction model. The AROC of the diabetes risk tool was 0.78 (95% CI, 0.76–0.81) and HL χ2 statistic was 4.1 (P = 0.85). Using a score ≥ 12 (maximum, 35), the sensitivity, specificity and positive predictive value for identifying incident diabetes were 74.0%, 67.7% and 12.7%, respectively. The AROC and HL χ2 statistic in the two independent validation cohorts were 0.66 (95% CI, 0.60–0.71) and 9.2 (P = 0.32), and 0.79 (95% CI, 0.72–0.86) and 29.4 (P < 0.001), respectively.Conclusions: This diabetes risk assessment tool provides a simple, non-invasive method to identify Australian adults at high risk of type 2 diabetes who might benefit from interventions to prevent or delay its onset.

Lei Chen MD, MMed · Dianna J Magliano BAppSci(Hons), MPH, PhD · Beverley Balkau PhD · Stephen Colagiuri MD, FRACP · Paul Z Zimmet MD, PhD, FRACP · Andrew M Tonkin MB BS, MD, FRACP · Paul Mitchell MD, PhD, FRANZCO · Patrick J Phillips MB BS, MA, FRACP · Jonathan E Shaw MD, MRCP, FRACP

Historically, the Australian Defence Force (ADF) has sourced all its blood supplies from the Australian Red Cross Blood Service. Recent ADF operations in the Middle East have highlighted a need to rely on other nations’ blood supply systems. In 2008, the ADF embedded a surgical and intensive care team into the Netherlands-led forward health facility at the Uruzgan Medical Centre at Tarin Kowt in Afghanistan. To date, three teams have provided 2-month rotations as part of the North Atlantic Treaty Organization International Security Assistance Force in Afghanistan. The Netherlands armed forces use a sophisticated system for supply of liquid and frozen blood products (frozen red cells, plasma and platelets). We review Australian experience with the Dutch system of supplying blood products for major trauma resuscitation in Afghanistan.

Susan J Neuhaus CSC, FRACS, PhD · Ken Wishaw MB BS, FANZCA · Charles Lelkens MD, SBB(ASCP)

Objective: To assess whether the components of the Healthy Kids Check (HKC), a preschool screening check recently added to the Australian Government’s Enhanced Primary Care Program, are supported by evidence-based guidelines or reviews.Data sources: Guideline and MEDLINE databases were searched for guidelines and systematic reviews published between 2000 and 2008 that were relevant to screening, prevention or well-child care in primary health care, and including children of preschool age. Search subjects reflected the HKC components: growth, weight, obesity, vision, hearing, oral health, enuresis, encopresis, allergic disease and food allergies.Study selection: 34 relevant guidelines or reviews were retrieved.Data extraction: For each component of the HKC, guidelines addressing the presumed rationale for screening, or the test or tool required to implement it, were reviewed. Relevant evidence-based and consensus-based guideline recommendations were assessed as either supporting or opposing components of the HKC, or stating that the evidence was insufficient to recommend screening of preschool children.Data synthesis: Guidelines were often inconsistent in their recommendations. Most of the components of the HKC (eg, screening for chronic otitis media and questioning about toilet habits) are not supported by evidence-based guidelines relevant to the primary care setting, though a number of consensus-based guidelines are supportive.Conclusions: There is currently a dearth of evidence relevant to child health surveillance in primary care. The components of the HKC could be refined to better reflect evidence-based guidelines that target health monitoring of preschool children.

Karyn E Alexander MB ChB, FRACGP, MPH · Danielle Mazza MD, FRACGP, DRANZCOG

Objective: To determine the applicant characteristics that influence success at each application stage for entry to the University of Adelaide Medical School.Design, setting and participants: Retrospective analysis of characteristics associated with a successful outcome to an undergraduate-entry medical school for 6699 applicants from four cohorts (2004–2007).Main outcome measures: Offer of an interview, offer of a place, and acceptance of a place in the medical school.Results: Female applicants were less likely to gain an interview (odds ratio [OR], 0.88; 95% CI, 0.78–0.99) but more likely to receive an offer of a place (OR, 1.33; 95% CI, 1.07–1.66). Older applicants were less likely than younger applicants (OR, 0.78; 95% CI, 0.71–0.86) and non-school leavers (applying after leaving school) were more likely than school leavers (applying while at school) (OR, 9.54; 95% CI, 6.16–14.78) to receive an offer of an interview. Applicants from areas of high socioeconomic status were more likely to gain an interview (quartile 1 v 4: OR, 0.55; 95% CI, 0.45–0.68). The more interviews an applicant had, the more likely he or she was to be offered a place (OR, 1.49; 95% CI, 1.34–1.66).Conclusion: This study indicates that some applicant characteristics have a significant influence on the success of an application at particular stages, but overall there does not appear to be a large or inherent systematic bias in the selection process at the University of Adelaide Medical School.

Caroline O Laurence BA(Hons), MHSM, PhD · Deborah A Turnbull MPsych(Clin), PhD, MAPS · Nancy E Briggs BSci, MSci, PhD · Jeffrey S Robinson BSc, MB BCh BAO, FRANZCOG

In the Australian public health system, access to elective surgery is rationed through the use of waiting lists in which patients are assigned to broad urgency categories. Surgeons are principally responsible for referring patients to waiting lists, deciding on the appropriate urgency category, and selecting patients from the waiting list to receive surgery. There are few agreed-upon criteria to help surgeons make these decisions, leading to striking differences between institutions in proportions of patients allocated to urgency categories. In other countries with publicly funded health systems, programs have been developed that aim to make prioritisation more consistent and access to surgery more equitable. As demand for health care increases, similar programs should be established in Australia using relevant clinical and psychosocial factors. Prioritisation methodology adapted for elective surgery may have a role in prioritising high-demand procedures in other areas of health care.

Andrea J Curtis BSc(Hons), PhD · Colin O H Russell MB ChB, FRACS · Johannes U Stoelwinder MD, FRACMA, FACHSE · John J McNeil PhD, FRACP, FAFPHM

Hospital funding based on achieving targets for numerical key performance indicators was implicated in Queensland’s Bundaberg Base Hospital scandal and has driven hospital data fraud in Victoria and New South Wales. Nationally uniform legislation is required to make health service reporting standards consistent and to criminalise public sector data fraud. Urgent action is needed to develop realistic outcome measures that base hospital funding more on the quality and safety of patient care and less on patient throughput numbers.

Antony Nocera FACEM, MSc(Emergency Planning and Disaster)

McKittrick–Wheelock syndrome is a rare but recognised complication of hypersecretory rectosigmoid villous adenoma. Fluid and electrolyte imbalances require close monitoring because of large-volume losses of water, sodium and potassium. We report an unusual presentation of the syndrome associated with the development of acute pseudo-obstruction of the colon, presumably due to electrolyte dysfunction and acute renal failure. (MJA 2010; 192: 225-227) Clinical recordA 68-year-old, white, previously fit and healthy man was transferred to our facility with oliguric acute renal failure. The patient reported 72 hours of lethargy, myalgia, generalised weakness and cramps, following 3 weeks of watery diarrhoea, with pink-stained mucous discharge. He reported 10 motions per day, and no abdominal pain or vomiting. Some bloating had been noted in the preceding 24 hours. On examination, the patient had a heart rate of 85 beats/min, blood pressure of 115/65 mmHg, a respiratory rate of 20 breaths/min, and a temperature of 36.2°C. Oxygen saturation was 95% on room air. He was clinically dehydrated, with reduced tissue turgor and dry mucous membranes. Normal breath sounds were audible. His abdomen was noted to be grossly distended and non-tender. No masses or organomegaly were evident. Digital examination demonstrated an enlarged rectum with no palpable mass. Initial laboratory investigations (Box 1) showed hyponatraemia, hypokalaemia and elevated urea and creatinine levels. Haemoconcentration was evident. Results of investigations for intrarenal causes of renal failure were negative. Analysis of arterial blood gases showed a transient respiratory alkalosis and net mild metabolic acidosis. There were multiple causative factors, suggesting the presence of an underlying metabolic alkalosis. Renal tract ultrasound showed no obstructing lesion, with normal kidney size and morphology. Plain imaging (Box 2) and computed tomography (CT) of the abdomen and pelvis with intravenous and oral contrast demonstrated distension of the small bowel up to 4 cm in diameter, with a caecal diameter of 10 cm. Fluid material filled the sigmoid colon and rectum. A non-obstructing, exophytic mass arising from the lateral wall of the rectum, measuring 5 × 9 × 7 cm, was noted. A presumptive diagnosis of colonic pseudo-obstruction due to fluid and electrolyte imbalance was made. The patient was aggressively rehydrated and administered N-acetyl cysteine. He was admitted to the intensive care unit immediately after his CT scans for continuous haemofiltration, vasopressor support and total parenteral nutrition (TPN). A rectal tube was inserted, which drained at a rate of 4 L/day. Haemofiltration and noradrenaline were ceased on Day 2 and TPN on Day 3. Renal function and serum biochemistry normalised by Day 4. Colonoscopy revealed an exophytic, pedunculated tumour about 10 cm long, located 10 cm from the anal sphincters. The large bowel was successfully decompressed. A biopsy of the lesion demonstrated tubulovillous adenoma. The rectal tube was removed on Day 5, and the patient, having opened his bowels, was transferred to the ward. Stool cultures were negative for viral or bacterial pathogens. Loperamide and codeine phosphate were introduced, with effect. Given the patient’s recent renal impairment, indomethacin was not commenced. The patient was discharged home on Day 10. Staging magnetic resonance imaging of the pelvis performed on the day of discharge clearly demonstrated a large, sessile tumour arising from the left rectal wall (Box 3). Appearances were thought to be consistent with a T2 lesion. After 3 weeks of outpatient convalescence, the patient returned for elective low anterior resection, which revealed a large, exophytic lesion within the rectum (Box 4). Histopathological examination of the resected specimen (Box 5) confirmed hypersecretory tubulovillous adenoma with low-grade dysplasia. DiscussionMcKittrick–Wheelock syndrome was described in 1954 and is a rare complication of villous adenoma.1 It is typified by large-volume secretory diarrhoea, prerenal acute renal failure, and severe electrolyte dysfunction (primarily hyponatraemia, hypochloraemia, hypokalaemia and metabolic acidosis). The causative lesion is usually in the rectosigmoid and is normally over 4 cm in diameter.2 One series of 18 patients described tumours ranging between 7 cm and 18 cm.3 Roughly 2% of patients with rectosigmoid villous adenoma will develop hypersecretory complications.4 Cellular composition of non-secretory and secretory villous adenomas differs markedly. Light microscopy of non-secretory villous adenoma reveals relatively few goblet cells within the tumour epithelium, while much of the epithelial architecture of secretory adenomas is composed of these mucin-secreting structures. It has been postulated that the large surface area of the lesion participating in mucin production is a contributing factor to the volume of diarrhoea. The distal location of these lesions means there is a minimal area of normal colonic mucosa remaining to allow fluid absorption.5 The electrolyte composition of mucin secreted by abnormal cells within the causative lesion is of interest. Whereas normal bowel absorbs sodium and water and secretes potassium, segments of intestine affected by villous adenoma have been found to secrete water, sodium and potassium. Absorptive capacity was largely unchanged. In both cases, net movement of water was directly related to net movement of sodium. There was no relationship between net movement of water and potassium loss.6 The cause of this abnormal secretory function has been postulated to be secretagogue-mediated. Rectal effluent from a patient with villous adenoma of the rectum demonstrated prostaglandin E2 (PGE2) levels three to six times higher than normal.7 Tissue from villous adenoma and carcinoma synthesises more PGE2 than normal colonic mucosa. Mucosa adjacent to adenomatous polyps has been found to be unaffected by this, but carcinoma-associated mucosa was demonstrated to synthesise larger amounts of PGE2.8 These secretagogues are active at sites containing the prostaglandin synthetic pathway. Non-reversible cyclooxygenase-inhibiting agents have been used to reduce PGE2 production, and consequently loss of sodium and water through the rectum.9 Cyclic nucleotides have also been implicated.10 It has previously been suggested that elevated PGE2 levels may contribute to the adenoma–carcinoma sequence,11 explaining the beneficial role of non-steroidal anti-inflammatory drugs in preventing colorectal cancer as well as controlling diarrhoea. The presence of colonic pseudo-obstruction added another level of complexity to our case.12 Given the pathophysiology of hypersecretory villous adenoma and the predisposing factors for pseudo-obstruction, this association is not unexpected. Less than 5% of patients will develop colonic pseudo-obstruction idiopathically.13 In an analysis of 378 patients with pseudo-obstruction, 16 cases (4.23%) were precipitated by acute renal failure, and a further 15 (3.97%) by electrolyte dysfunction.14 In another retrospective analysis of 48 cases, 83% of patients were found to have some degree of electrolyte dysfunction.15 The mechanism by which homeostatic derangement causes pseudo-obstruction remains poorly understood. 1 Relevant admission laboratory results* Result Reference range Serum biochemistry Sodium (mmol/L) 120 135–145 Potassium (mmol/L) 3.2 3.5–5.0 Chloride (mmol/L) 86 99–107 Bicarbonate (mmol/L) 18 24–32 Urea (mmol/L) 54.6 4.0–9.0 Creatinine (μmol/L) 580 60–105 Glucose (mmol/L) 7.5 4.0–7.0 Osmolality (mmol/kg) 331 275–300 Corrected calcium (mmol/L) 2.14 2.23–2.50 Magnesium (mmol/L) 1.96 0.7–1.1 Phosphate (mmol/L) 5.15 0.6–1.3 Urine biochemistry Osmolality (mmol/kg) 383 50–1200 Sodium (mmol/L) 8 Variable Protein (g/L) 1.42 0.01–0.14 Full blood examination Haemoglobin (g/L) 191 122–170 White cell count (× 109/L) 15.8 4.6–10.5 Platelets (× 1012/L) 326 150–400 Haematocrit (%) 0.53 0.36–0.49 Mean cell volume (fL) 83 80–97 Neutrophils (× 109/L) 13.4 1.9–8.0 Arterial blood gas pH 7.47 7.35–7.45 PaCO2 (mmHg) 25 35–45 PaO2 (mmHg) 126 75–99 Base excess − 4 − 3 to 3 Other Albumin (g/L) 47 35–52 * Some initial volume resuscitation with normal saline had taken place prior to investigations. 2 Erect (A) and supine (B) abdominal x-rays taken on admission Note the uniform dilation of the large bowel, with multiple air–fluid levels (arrows). 3 Sagittal (A) and coronal (B) magnetic resonance images of the causative lesion Note the large mass occupying the mid to distal rectum, arising from the left rectal wall (arrows). The protruding mass extends almost to the anal verge. These images show no evidence of involvement of perirectal structures. The darkened signal on T2 images is caused by large amounts of mucin within the lesion. H = head. F = feet. A = anterior. P = posterior. R = right. L = left. 4 Macroscopic photograph of rectal villous adenoma found at operation The causative lesion was 12 cm in diameter, with elevation of 5 cm. 5 Low-power (A) and high-power (B) microscopic photographs of the causative lesion These images demonstrate features consistent with villous adenoma with low-grade dysplasia. Of particular interest is the large volume of gelatinous mucin produced by the lesion, as well as the high population of goblet cells evident along the epithelial border of the lesion (arrows).

Lachlan F Miles MB BS(Hons) · Christopher J Wakeman MB ChB, MMedSci, FRACS · K Chip Farmer MB BS(Hons), FRACS, FCSSANZ

Clinical record An 88-year-old man presented to our emergency department with sudden loss of vision in his right eye. Past ocular history included amblyopia in his right eye and bilateral neovascular age-related macular degeneration (AMD). Previously recorded best corrected visual acuities were 6/120 and 6/18 in his right and left eye, respectively. The patient’s past medical history included acute myocardial infarction, atrial fibrillation, hypertension, hypercholesterolaemia and polymyalgia rheumatica. He had no history of diabetes, cerebrovascular accident or transient ischaemic attack. His medications included warfarin, aspirin, metoprolol, perindopril and simvastatin. His international normalised ratio (INR) had ranged between 1.3 and 2.3 over the preceding 12 months, with a target of 2.0. Visual acuity in the right eye was count fingers. Dilated slit lamp examination revealed a large submacular haemorrhage with associated vitreous haemorrhage (Figure A). An electrocardiogram showed atrial fibrillation with a heart rate of 72 beats/min. His blood pressure was 110/80 mmHg. His INR was 2.8. The eye was managed conservatively and, following resolution of the vitreous haemorrhage, vision remained at count fingers. Four months later, the patient reported sudden loss of vision in his left eye. Visual acuity was light perception, and dilated fundus examination revealed dense subretinal and associated vitreous haemorrhage (Figure B). The patient was still taking warfarin, and his INR at this time was 2.7. As this had been his better eye, he underwent pars plana vitrectomy and clearance of the vitreous haemorrhage. After surgery, his visual acuity was count fingers. After further discussion with the patient’s cardiologist, a decision was made to cease warfarin. A: Fundus photograph of the right eye at presentation, showing macular subretinal and intraretinal haemorrhage. The mild haziness of the photograph is indicative of vitreous haemorrhage. B: Fundus photograph of the left eye at the time of presentation of visual loss in this eye. Extensive subretinal haemorrhage is seen in the macula. Again, the haziness of the photograph is indicative of vitreous haemorrhage. This report highlights a potential interaction between a commonly used anticoagulant, warfarin, and an increasingly common ocular condition — AMD. The risk of AMD increases with age, with prevalence reaching 20% of people aged over 75 years in white populations.1 Neovascular (“wet”) AMD accounts for 10%–20% of cases,2 and for 80%–90% of patients who become legally blind from AMD.3 Peripheral vision is typically retained, and most patients are able to maintain a degree of functional independence. Development of large subretinal and vitreous haemorrhages in neovascular AMD is uncommon. Treatment options are limited and, even with surgical intervention, visual outcomes are in the range of light perception to counting fingers only, with significant loss of paracentral and peripheral vision.4 The functional effects are therefore profound. Previous studies have demonstrated an association between the use of anticoagulant medication, particularly warfarin, and large intraocular haemorrhages among patients with neovascular AMD.5,6 The largest of these, a retrospective case–control study comprising 100 patients, found that those with massive intraocular haemorrhage were 11.6 times more likely to be taking anticoagulant medication.6 Among these patients, INR ranged from 3.0 to 4.0. Patients with massive haemorrhage were twice as likely to be taking aspirin, although the significance of this finding is less certain, as the lower limit of the 95% confidence interval was less than 1. No patient was taking anticoagulants and aspirin concurrently.6 In our patient, the role of concurrent aspirin therapy is unclear, as there is no evidence in the literature to support or refute the hypothesis that concurrent antiplatelet therapy may have contributed to the development of haemorrhage. However, both instances of haemorrhage were noted to occur at times when his INR was high compared with those recorded over the previous 12 months. Our patient was taking aspirin at all times during this period. Although it is possible that intraocular haemorrhage may have occurred purely as a result of his underlying neovascular AMD, the temporal relationship between the development of the haemorrhages and the high INRs strengthens the case for the implication of warfarin therapy as a contributing factor. Application of the Naranjo probability scale7 indicates that this adverse drug event was probable (Naranjo score, + 5). The association between anticoagulant therapy and intraocular haemorrhage is of key importance for several reasons. Firstly, massive intraocular haemorrhage is an important diagnosis to consider in an anticoagulated patient who presents with loss of vision, and who has a background of neovascular AMD. Secondly, patients with neovascular AMD in one eye are at risk of developing neovascular AMD in the second eye,8 and therefore at risk of developing large intraocular haemorrhages in both eyes if long-term anticoagulation is continued. There are several clinical situations in which the indication for anticoagulation is relative. There are key roles for the ophthalmologist, cardiologist, and general practitioner to ensure that an appropriate risk–benefit evaluation is made before initiating anticoagulant therapy for patients with neovascular AMD. Patients taking anticoagulants who develop neovascular AMD, and in particular those with neovascular AMD who are taking anticoagulants and who develop intraocular haemorrhage in one eye, should have their therapy carefully re-evaluated. Importantly, awareness of the poor outcomes of intraocular haemorrhage in neovascular AMD, the role of anticoagulants as a risk factor, and effective communication between health professionals may help reduce the incidence of this devastating complication. Lessons from practice Patients with neovascular age-related macular degeneration (AMD) have a small but significant risk of intraocular haemorrhage, which may be increased in severity if patients are taking anticoagulant medication. The outcomes of intraocular haemorrhage are poor, with significant deterioration in paracentral and peripheral vision, and subsequent implications for ability to maintain functional independence. When considering anticoagulation therapy for patients with neovascular AMD, liaison between the general practitioner, cardiologist and ophthalmologist will ensure that an appropriate risk–benefit evaluation is made. If patients who take anticoagulant medication develop signs of neovascular AMD, it is essential that the ophthalmologist liaise with the GP and/or cardiologist to ensure that the need for anticoagulation, and the target international normalised ratio, are carefully reviewed.

Rajeev Chalasani MB BS · Salmaan Qureshi FRANZCO

To the Editor: The recent rapid increase in popularity of low-carbohydrate (“low-carb”) beers in Australia, such as Foster’s Pure Blonde and Lion Nathan’s Hahn Super Dry, may represent an insidious health risk. The perception that low-carb beers represent a healthy alternative may result in some consumers: confusing low-carb beers with low-alcohol beers; believing that there will be a significant health benefit associated with consumption of low-carb beers (such as weight loss); drinking more beer in the belief that there are fewer health consequences associated with low-carb beers; or drinking low-carb beer in situations where the consumption of regular beer may be contraindicated because of health conditions such as diabetes or cardiac vulnerability. Particularly vulnerable risk groups include younger people and especially young women, who are often highly body image-conscious, as well as others with weight or health problems. Nutritional information for some of the major beers on the market in Australia is shown in the Box.1-3 The new generation of low-carb beers contain about 0.9 g of carbohydrate per 100 mL. However, there is little, if any, difference in either the amount of alcohol or the total energy content of traditional and low-carb beers, suggesting “low-carb” may not be a nutritionally significant improvement. Given that alcohol is a known cause of short- and long-term problems such as cancer, cirrhosis of the liver, strokes and violent behaviour, we contend that the alcohol content of beer is a far more important health issue than its energy content. Additionally, the alcohol content itself contributes directly to energy intake (1 g of alcohol contributes 29.8 kJ of energy, compared with sugar’s 15.4 kJ).4 Consuming alcohol may also indirectly lead to weight gain because of its association with unhealthy eating behaviour, such as increased snacking, junk food consumption and overeating.5 The Box clearly demonstrates that drinkers are better off consuming low-strength beers in terms of both alcohol content and energy intake. Recognising this fact, the European Parliament adopted the resolution that “Beverages containing more than 1.2% by volume of alcohol shall not bear health claims”.6 We believe that the Australian Government, particularly through its current Review of Food Labelling Law and Policy, should move quickly to enact similar legislation to protect the Australian public from the marketing claims of brewing companies. The message should be made explicit: low-carb beers are not a “healthy choice”. Nutritional information for major beers on the market in Australia1-3 Beer Alcohol by volume Carb (g/100 mL) Energy (kJ/100 mL) Full strength Redback 4.7% 3.6 172 Hahn Premium 5.0% 3.2 172 Cascade Pale Ale 5.0% 3.0 170 Crown Lager 4.9% 3.1 169 Cascade Premium Lager 5.0% 3.0 169 Foster’s Lager 4.9% 3.1 168 Victoria Bitter 4.6% 3.0 165 Carlton Black 4.4% 3.3 161 Tooheys New 4.6% 3.1 161 Tooheys Extra Dry 5.0% 2.5 161 Melbourne Bitter 4.6% 2.9 158 Tooheys Old 4.4% 3.0 156 Carlton Draught 4.6% 2.7 155 Swan Draught 4.5% 2.7 153 XXXX Draught 4.5% 2.1 147 Mid–low strength XXXX Gold 3.5% 1.9 121 Hahn Premium Light 2.6% 3.1 119 Carlton Sterling 2.5% 3.1 114 Cascade Light 2.6% 3.0 114 Hahn Super Dry 3.5 3.5% < 1.0 104 Low-carb Carlton Dry 4.5% 1.9 139 Bondi Blonde 4.5% < 2.0 130 Tooheys Maxim 4.6% 1.6 126 Hahn Super Dry 4.6% 0.9 126 Pure Blonde 4.6% 0.9 125 Carb = carbohydrate.

Peter G Miller · Stephen P McKenzie · Florentine P de Groot · Sondra L Davoren · Evie R Leslie

To the Editor: Influenza causes around 8% of community-acquired pneumonia (CAP) episodes,1 and during the (H1N1) 2009 influenza pandemic, concurrent bacterial infections were detected in up to 29% of fatal infections.2 Determining microbial aetiology of CAP can guide antibiotic and antiviral therapy. To investigate the usefulness of microbiological diagnostic testing for CAP, we undertook a retrospective review of our pathology department’s electronic database of patients admitted with CAP to a tertiary referral centre (365 beds) and two suburban teaching hospitals (314 and 280 beds) between 1 May 2007 and 30 April 2008. Inclusion criteria were: International Classification of Diseases, 10th revision codes J09–J22 (respiratory tract infections); age ≥ 18 years; and consolidation on a chest radiograph performed within 48 hours of admission. Exclusion criteria were: hospitalisation within the previous 14 days; admission to a unit managing predominantly immunosuppressed patients; HIV infection; active tuberculosis; chest injuries; and previous inclusion in the study. Basic demographic data and microbiological investigation results were collected. We adopted the Australian CAP Study’s criteria for aetiology and classification of good-quality sputum.1 Change in management was indicated for patients with bacteria not covered by empiric regimens recommended in Therapeutic guidelines: antibiotic, version 13, or organisms with public health and infection control implications.3 Continuous variables were analysed using either Student’s t test or the Wilcoxon rank-sum test, and categorical variables with the Fisher exact test. Statistical significance was set at P < 0.05. From 2436 admissions, 341 patients met inclusion criteria. Mean age was 71.1 (SD, 17.1) years, and 72 patients (21.1%) were in residential care. Most patients (251; 73.6%) had investigations to determine aetiology (Box). Ninety-three organisms were identified from 83 patients (33.1%), most commonly Streptococcus pneumoniae (33; 13.1%), Haemophilus influenzae (14; 5.6%), influenza (11; 4.4%) and Legionella spp (9; 3.6%). Good-quality sputum taken within 8 hours of presentation had the highest diagnostic yield (47.1%). Changes to management were indicated for 37 patients (14.7%). Aetiology was identified more often in the suburban hospitals, where S. pneumoniae and Legionella spp were more common than in the tertiary centre (27.7% v 8.1% and 9.2% v 1.6%, respectively; P = 0.001). Patients in the suburban hospitals were younger and less likely to be in residential care than those in the tertiary centre (mean, 67.6 v 72.6 years and 13.7% v 24.3%, respectively; P ≤ 0.03). The Australian antibiotic guidelines recommend appropriate investigations to determine aetiology of CAP.3 Our analysis suggests that usefulness of microbiological investigations varies between different patient populations, and their value may be maximised by using algorithms similar to the recommendations for CAP investigations in United States guidelines.4 Contrary to widespread belief that microbiological diagnostic tests for CAP are low-yield and not helpful, we found that aetiology could be established in up to 55% of patients and a change in management made in 15% by using a combination of diagnostic tests. Our findings should be generalisable to other parts of Australia, as the aetiologies we observed mirror those seen in the Australian CAP Study.1 Diagnostic yield of investigations used to determine microbial aetiology for patients hospitalised with community-acquired pneumonia No. positive/no. tested (% positive) Investigation Suburban hospitals Tertiary centre Total Sputum microscopy, culture and sensitivities 14/40 (35.0%) 23/103 (22.3%) 37/143 (25.9%) Blood culture 5/42 (11.9%) 7/131 (5.3%) 12/173 (6.9%) Urinary antigen test Streptococcus pneumoniae* 14/40 (35.0%) 11/105 (10.5%) 25/145 (17.2%) Legionella pneumophila serogroup 1* 4/39 (10.3%) 1/104 (1.0%) 5/143 (3.5%) Respiratory multiplex PCR† 1/6 (16.7%) 6/17 (35.3%) 7/23 (30.4%) Bronchoscopy‡ 0/2 3/12 (25.0%) 3/14 (21.4%) Serology§ 4/27 (14.8%) 7/66 (10.6%) 11/93 (11.8%) Total patients investigated 36/65 (55.4%) 47/186 (25.3%) 83/251 (33.1%) PCR = polymerase chain reaction. * P = 0.02 for comparison of % positive between hospitals. † Nasopharyngeal swabs tested for influenza A and B, picornavirus, parainfluenza, adenovirus and respiratory syncytial virus. ‡ All bronchoscopy specimens cultured for Legionella spp, bacterial and fungal pathogens, and other investigations as requested by clinicians. § Serological tests for influenza A and B, Legionella spp, Mycoplasma pneumoniae, Chlamydophila spp and Coxiella burnetii.

Adrian R Tramontana · Vincent Sinickas

To the Editor: We present this case to highlight the differential diagnosis of afebrile seizures in patients from many asset-poor nations. A 3-year-old Congolese girl presented with sustained loss of consciousness after a prolonged generalised seizure. She had migrated, with her family, 12 months previously after a long period in a Zambian refugee camp. She was intubated briefly and given intravenous benzodiazepines. She made an uneventful recovery; she was discharged from hospital after 2 days. This was her first seizure and there was no history of fever, trauma or poisoning. The parents declined long-term anticonvulsants. Apart from mild malaria, she had been previously well and showed normal development. HIV serology and results of blood films for malarial parasites were negative; other blood tests, including an eosinophil count, were normal. Cerebral magnetic resonance imaging (MRI), performed because the diagnosis was unclear and the patient had had a prolonged seizure, revealed a single 8 mm cyst, with an enhancing wall and surrounding oedema, in the left frontal lobe. The cyst contained a scolex, pathognomonic of neurocysticercosis (Box). There were multiple foci throughout the brain, indicating active and resolving cysts. Serology results for Taenia solium were negative at presentation and 3 months later. The child was treated with 8 days of albendazole and 3 days of dexamethasone. Repeat MRI 2 months after presentation showed significant improvement, with a residual 3 mm calcified focus. The child has remained seizure-free for 18 months. Neurocysticercosis is caused by larvae of the pork tapeworm T. solium, which may encyst in the brain, eye or spinal cord, after ingestion of ova-contaminated food or water.1 In contrast, ingestion of encysted larvae (cysticerci) in undercooked meat results in intestinal infection with the adult tapeworm.1 Neurocysticercosis is common in many asset-poor countries, including those in Asia and sub-Saharan Africa from where many people in humanitarian refugee programs originate.2 In areas where it is endemic, T. solium is a leading cause of epilepsy in children and adults.3 The diagnosis of neurocysticercosis is difficult and the diagnostic differential is broad. Cerebral imaging showing typical lesions containing a scolex is diagnostic. T. solium serology is insensitive, especially in children with few cysts. Anticercal antibodies or cysticercal antigens in the cerebral spinal fluid are helpful, but these investigations are not widely available (they are available from the Centers for Disease Control and Prevention, Atlanta, United States). Treatment with anthelmintics is controversial; parasites may die spontaneously and treatment may cause local inflammation (reduced by steroids), which potentially exacerbates seizures or causes local tissue damage.4 Ocular cysticercosis should be excluded before anthelmintic treatment as the resultant inflammation may compromise sight; surgical excision should be considered if ocular cysticercosis is present.4 Empirical anthelmintics, often given before departure or following resettlement to people at risk, may potentially precipitate seizures.5 We treated this child with albendazole as there were multiple lesions likely to contain live parasites, and because anticonvulsants were declined. This case highlights that neurocysticercosis is a possible treatable cause of afebrile seizures in patients migrating from, or with a history of visiting, endemic areas, including resettled refugees. Clinicians in affluent countries are often unfamiliar with the disease, yet are managing increasing numbers of people at risk. Misdiagnosis is of particular concern because brain imaging is not routinely performed in children presenting with their first afebrile seizure. Magnetic resonance image of brain of 3-year-old girl showing cysticercus Encysted scolex of Taenia solium, surrounded by enhancing wall and significant oedema, in left frontal cerebral lobe.

Juliette M Lucey · James McCarthy · David P Burgner

To the Editor: Two recent publications have described programs of carrier testing for cystic fibrosis (CF) gene mutations.1,2 The authors conclude that CF carrier testing of women in early pregnancy and their partners, as well as couples contemplating pregnancy, can successfully identify those who are at risk of having a child with CF and provide them with reproductive choices. The authors use these proof-of-concept studies, in the absence of Australian economic data, to call for all couples to be offered CF carrier testing that is supported by government funding. Although reproductive choice is clearly an individual’s right, what obligation does the community have regarding government funding of specific services to generate information that might assist such couples? Genetic screening policies have often been determined on the basis of technological capability, rather than through a rigorous evidence-based review process.3 Decision making should also take into account evidence of clinically effective screening programs, ethical principles, and opportunity costs, given the limited resources available in the health sector. A simple economic analysis of these publications highlights some issues that need to be addressed. Massie and colleagues identified nine carrier couples by screening 3200 individuals (3000 females) before conception or during early pregnancy (CF carrier frequency, one in 30). Two of the nine carrier couples had affected pregnancies, which equates to a cost of $300 000 per CF case. In Christie and colleagues’ dataset of 1000 individuals, 73% had no family history of CF; 27 of these individuals carried CF mutations, and two carrier couples but no affected pregnancies were identified. Based on population gene frequency statistics (CF carrier frequency, one in 25; 75% of CF gene mutations being p. F508del),1 Massie et al’s screening model2 would, on average, require 3585 women to be screened to detect one affected pregnancy, costing about $740 000. Christie et al’s expanded one-step model1 would require about 3763 couples to be screened to detect one affected pregnancy, at a cost of more than $430 000. Among the 270 individuals with a family history of CF who were screened in the latter model, 126 were carriers of CF mutations (carrier frequency, one in two). It is clear that cascade screening of those with a family history would be a more effective strategy. There is an ethical argument that projected economic benefits from the termination of affected fetuses should not play a role in decisions to offer testing.4 Nevertheless, technological capability needs to be considered together with evidence of cost-effectiveness and community acceptance before public funding of community CF carrier screening can be justified.

Peter C O’Leary · Susannah J Maxwell · Leanne M Youngs · Kate J Brameld · Ian R Walpole

In reply: Our aims in publishing the outcomes of offering cystic fibrosis (CF) carrier testing to couples were to demonstrate the high acceptability rate and report the reproductive choices made by high-risk couples. Not all decisions resulted in termination. O’Leary and colleagues rightly raise the question of screening costs. Laboratory costs will reduce with economies of scale and centralisation of testing. The recent release of a position paper on population screening for CF by the Human Genetics Society of Australasia1 will influence the demand for testing. It recommends that all couples intending to have children, and women in early pregnancy and their partners, be made aware of the availability of CF carrier testing, and that couples should be offered testing for 10 CF transmembrane conductance regulator gene mutations using an expanded one-step or two-step model. O’Leary and colleagues suggest that cascade testing of those with a family history of CF would be a more effective strategy. However, only 10% of children born with CF have a family history.2 Studies have demonstrated that costs of CF screening are less than the averted medical care costs associated with fewer births of infants with CF.3-5 Although economic considerations are important, these should not form the primary goal of any screening program.

Louise M Christie · Angela J Ingrey · Gillian M Turner · Anne L Proos · Gloria E Watts

To the Editor: Hellard and Wang1 are correct in emphasising the importance of the general practitioner in the management of hepatitis C virus (HCV) infection. As the authors note, HCV infection is a considerable source of morbidity and mortality in the community, and the infection may cause a substantial burden of illness in the future if it is not appropriately managed. The GP plays a pivotal role in managing HCV infection, being the first and most likely point of contact for patients. However, Hellard and Wang fail to note that the GP’s most useful role is to inform patients that “alcohol abstinence is strongly recommended before and during antiviral therapy”.2 The well recognised role of alcohol in disease progression is emphasised in the position papers of both the American Gastroenterological Association and the United States National Institutes of Health.2,3 From a public health perspective, it is difficult to think of a more cost-effective approach to the management of such a public health issue.

Anne E Duggan · John M Duggan

In reply: Duggan and Duggan are correct to highlight the well recognised role of alcohol consumption in progression of hepatitis C virus (HCV) infection. Alcohol consumption has been found to increase viral load and accelerate hepatic fibrosis in HCV infection.1,2 While studies have reported that a history of alcohol consumption adversely affects treatment outcomes (with some reporting a dose–response relationship),3,4 treatment success has also been reported among patients who continue to consume moderate amounts of alcohol during treatment.5 Although there are biologically plausible mechanisms through which alcohol consumption might negatively affect treatment, low rates of treatment success among drinkers may also be related to lack of adherence to treatment regimen in this population.1 To date, no study has specifically measured the effect of alcohol consumption during treatment while adequately controlling for the effects of compliance, disease progression and baseline viral load. Until studies are undertaken that measure the direct effect of alcohol consumption on treatment success, while adjusting for compliance, it seems reasonable to advise patients to decrease their level of alcohol consumption before and during HCV treatment. However, given that some patients have successfully completed treatment without abstaining from alcohol consumption, this should not be an automatic exclusion criterion.

Margaret E Hellard · Yung-Hsuan J Wang · Rachel Sacks-Davis

To the Editor: The recent letter by Cox, about transfer of pregnant women from remote communities to Cairns for birthing,1 mirrored my experiences while working in general practice and psychiatric community outreach in rural Australia for many years. The removal of people from their familiar surroundings (especially for extended periods) in itself exacerbates health problems, even more so when they are already hindered by impaired socioeconomic status or ethnic disadvantage. Almost always, the security of their attachment and capacity to maintain resilience are strained. Furthermore, this displacement often occurs in emotionally charged or threatening health situations, where it is likely to be most damaging: childbirth, treatment of life-threatening disease caused by malignant neoplasm or cardiovascular disease, and management of mental disorders or substance misuse. The increasing concentration of “expert” treatment centres in fewer and fewer (usually metropolitan) centres, together with the degradation and de-skilling of rural and remote services that I have observed for the nearly 30 years I have worked in Australia, are sad. However, even worse is the failure of government to do anything to reverse the trend, despite repeated hand-wringing and talking about the rural health “problem”.

Robert D Craig

To the Editor: The Australian Medical Council recognises the importance of clinical experience in general practice for all medical students.1 In their recent article in the Journal, Vickery and colleagues identify three significant barriers to clinical teaching by Australian general practitioners: time, space and opportunity costs.2 They suggest that General Practice Super Clinics will be well placed to address the issue of space and, with additional funding, could also overcome the barriers of opportunity cost and lack of time. The latter claim may be true, but we need to invest in all teaching practices, not just in Super Clinics. The Australian Government is currently committed to establishing 35 Super Clinics. Even if more are set up in the future, it is difficult to see how they will ever make a major contribution to providing general practice placements for the 3000-plus students entering medical training each year. There are many high-quality general practices across Australia that have been committed to teaching for years. For this, they receive a $200 Practice Incentives Program payment per student per day. This amount has not increased since 2004, and is widely seen as insufficient to meet practice teaching costs. There is an urgent need to increase the sessional payment for teaching to an amount that realistically reflects the time and opportunity costs to practices. In addition, a national fund for capital investment in teaching practices would help address the third barrier that Vickery et al identify: many excellent practices are unable to provide student placements due to lack of space.

Timothy P Usherwood

A 29-year-old woman presented with a 19-day history of blurred vision and intolerance to bright light after a presumed viral illness (a sore throat and fever resolved 4 days before the onset of other symptoms). At presentation, she reported a dry mouth, mild constipation, abdominal bloating and hesitancy of micturition. Results of a clinical examination were normal apart from dilated, slightly asymmetric pupils (Figure, A), non-reactive to light and accommodation. The patient’s condition gradually improved over the subsequent 6 months. Tests of heart rate and blood pressure showed normal cardiovascular autonomic function. Thermoregulatory sweat testing was undertaken by applying a starch and iodine paste to the skin; this changes colour to purple in the presence of sweat. Results showed an absence of sweating in the patient’s arms and legs (Figure, B and C) compared with an age-matched control volunteer (Figure, D and E). These findings support a diagnosis of a subacute cholinergic neuropathy causing parasympathetic failure, which, in the clinical context, is likely to represent an uncommon variant of Guillain–Barré syndrome.1 Figure

Robert D Henderson · Jeyaraj D Pandian · Kaye M Dalton · John M Bradfield

Never too late It’s generally accepted that most patients diagnosed with lung cancer are in the last months of their lives.1 However, a meta-analysis of 10 observational studies has determined that for patients with early stage lung cancers there may be a significant survival benefit if they stop smoking even after (rather than before) diagnosis.2 The five-year survival in these post-diagnosis “quitters” was in the order of 60-70% compared with about 30% in those who continued to smoke. Further, it was suggested that this benefit was due to a reduced likelihood of cancer progression rather than a reduction in cardio-respiratory deaths. In a linked editorial,1 Treasure and Treasure said that the sooner in their lives people stopped smoking the better, but the real gain would be in stopping young people from starting altogether. 1. BMJ 2010; 340: b5630 2. BMJ 2010; 340: b5569 Dental wisdom Over many decades, the regular extraction of wisdom teeth (third molars) was seemingly based on a multitude of dental health care practitioners’ beliefs, values, biases and anecdotal evidence. In today’s world of evidence-based medicine (and dentistry), such practices may be not only not evidence-based but also unethical, say Kandasamy and colleagues. In a review, they said that the removal of third molars primarily to avoid late incisor crowding is not supported by evidence; further, the procedure can lead to complications. They do acknowledge that there are clear indications for the removal of third molars associated with pathology; however, otherwise, these teeth are, generally speaking, best left alone and monitored periodically. Aust Dent J 2009; 54: 284-292 Death by negligence Out-of-hours primary care in the UK is coming under closer scrutiny as an inquest begins into the deaths of two patients, according to a news report in the BMJ. One patient had received an excessively high dose of diamorphine; the other had experienced a heart attack but was not sent to hospital. Both patients had been seen by the same doctor, who usually practised in Germany but had been flown to the UK to provide out-of-hours care. Since 2004, primary care trusts (rather than GPs) have been responsible for out-of-hours services in England; however, there is concern that trusts are not consistently monitoring the quality of care provided. Further, under European Union (EU) rules, doctors in the EU are free to work in other member countries without the stringent checks that apply to other foreign doctors. The doctor involved in these two cases was suspended from the UK medical register but allowed to go on practising in Germany. However, the doctor was prosecuted by German authorities for causing death by negligence, given a nine-month suspended sentence, and ordered to pay €5000. BMJ 2010; 340: c286 Beyond antibiotics Standard therapy for Clostridium difficile infection hasn’t changed since the 1970s — incongruously, antibiotics for an antibiotic-associated condition.1 However, adding monoclonal antibodies to the usual regimen of either metronidazole or vancomycin could significantly reduce recurrence, if not the initial severity, of infection. In a randomised placebo-controlled study involved 200 patients with current symptomatic infection, US researchers found that adding a single infusion of two neutralising, fully human monoclonal antibodies against C. difficile toxins A and B to usual treatment reduced the recurrence rate of C. difficile infection to 7% compared with 25% in the placebo group.2 However, there were no significant differences between the antibody and the placebo group in the severity of diarrhoea during the initial episode of C. difficile infection. The researchers had previously found: efficacy for the combined antibodies in a hamster model; and, safety, in a phase I study in healthy volunteers; they say this treatment now deserves further study. An editorialist said this novel approach to breaking the cycle of C difficile infection offered hope in the battle against this increasingly prevalent and difficult-to-manage disease.1 1. N Engl J Med 2010; 362: 264-265 2. N Engl J Med 2010; 362: 197-205 Dr Ann Gregory, MJA

Ann Gregory