Aspirin-induced asthma alert Doctors should routinely advise their patients with asthma about the possibility of aspirin-induced asthma, as it occurs more commonly than previously thought, say the authors of a systematic review. The advice should be tailored to the patient (eg, those with nasal polyps or chronic rhinitis are at high risk of aspirin-induced asthma and should avoid all products that contain aspirin or NSAIDs indefinitely). Australian researcher Jenkins and colleagues analysed pooled data from 21 trials, finding an overall pooled incidence of 21% (95% confidence intervals, 14% to 29%) for aspirin-induced asthma — about twice as high as previously reported. Their review also determined that cross-sensitivity to three commonly used NSAIDs (ibuprofen, naproxen and diclofenac) was present in most patients with aspirin-induced asthma. Cross-sensitivity to paracetamol occurred in only 7% of patients, and tended to be less severe. BMJ 2004; 328: 434-437 Downsize, get sick, and die? Finnish research has found major oragnisational downsizing (>18%) during the recession of the 1990s was linked to more sick leave in full-time, permanent municipal employees of four towns. It was also linked with more cardiovascular deaths, especially in the first few years. The municipalities downsized to cut costs, but legislation did not allow parallel cuts in the services provided. BMJ 2004; 328: 555-589 Children’s voices The days of children being seen and not heard may be over. According to a news item in the BMJ, a report from the UK Commission for Health Improvement says that many children and teenagers want to learn and participate more in decisions about their treatment. Commenting on their level of involvement, children were quoted as saying: "[The doctor] only explained it to my dad", and "[I] did not really understand, nobody explained what is going to happen to you to make you better". BMJ 2004; 328: 600 Trafficking: the human cost The Lancet recently examined health and human rights issues relating to the "trafficking" of people for indentured servitude, and especially of women and girls for sexual exploitation. Trafficked people may fear retribution or deportation and avoid health services, despite the threat to their own health (and others, via HIV/AIDS). Well-meaning acts on behalf of trafficked women have sometimes landed them in even worse situations; each woman’s assessment of her situation and risks to her safety should be respected. Lancet 2004; 363: 564, 565, 566 . . . and would you like some gout with that, sir? The US Health Professionals Follow-up Study has confirmed that eating meat and seafood increases the risk of gout, whereas consuming dairy products reduces it. Over 12 years, the study found 730 new cases of gout had developed among 47 150 men. Gout was more likely in men who had eaten more meat (at just under two servings a day, on average) and more seafood (a little more than about half a serving a day) than unaffected men. Those who consumed more dairy products, especially low-fat ones (eg, two glasses of skim milk per day), were less likely to develop gout. However, intake of purine-rich vegetables and total protein intake were not linked to an increased risk of gout. An accompanying article said that gout should be considered part of the current global epidemic of obesity, hypertension and diabetes. 1. N Engl J Med 2004; 350: 1093-1103 2. N Engl J Med 2004; 350: 1071-1073 Clinical statistics put simply With the current emphasis on evidence-based medicine, we're rapidly reaching the point where all clinicians simply must have some kind of grip on statistics. But perhaps this lies more in understanding what each test is designed to measure and in interpreting what the result will mean in practice rather than in knowing how to do the calculations. For example: when is a median value preferable to a mean? When is a statistically significant result clinically significant? And, what are the dangers inherent in subset analyses? Those seeking a straightforward, practical approach to these kinds of questions might like to look at Guller and DeLong’s vade mecum, prepared for surgeons as a no-nonsense way of launching into a potentially tricky operating field. J Am Coll Surg 2004; 198: 441-458 — Dr Ann Gregory, MJA

Ann Gregory

Rickets in children and osteomalacia in adults are caused by undermineralisation of bone, which increases its susceptibility to bending and fracture; treatment is with calcium, vitamin D or phosphate, depending on the specific mineral or vitamin deficiency. In Paget’s disease, osteoclasts are overactive and produce woven or “repair” bone, which is mechanically weaker than lamellar bone; treatment is with antiresorptive bisphosphonate drugs. Cancers can produce bone lysis through direct spread within the skeleton or production of endocrine parathyroid hormone-like factors; treatment is with a bisphosphonate, plus appropriate therapy for the cancer. Cancer can also produce hypercalcaemia if the capacity of the kidneys to excrete the calcium dissolved from bone is exceeded; treatment is with saline infusion to increase excretion and a bisphosphonate. Primary hyperparathyroidism is the other common cause of hypercalcaemia and is usually associated with a single parathyroid adenoma; it is best treated with parathyroidectomy. Hypocalcaemia may result from severe decrease in calcium absorbed or lack of parathyroid action; both are treated with calcium and vitamin D (ergocalciferol or calcitriol).

Richard L Prince FRACP, MD · Paul Glendenning PhD, FRACP

Can we solve a riddle by burying an illusion? Over the past 40 years, the prevalence of asthma appeared to rise inexorably in both the developed and the developing world. So the report by Robertson and colleagues in this issue of the Journal (page 273), showing a decline in reported symptoms in children since 1993,1 is to be warmly welcomed. It comes with supporting evidence, in the form of reduced hospital admissions for asthma in Victoria, but also with a catch. The prevalence of reported hay fever and eczema has increased over the same period. Why the prevalence of asthma increased and why it may now be stabilising or declining is baffling. Robertson et al suggest one possibility may be the increased use of daycare facilities. The “hygiene hypothesis” — the inverse relationship between microbial or infection exposure and allergic disease — was first suggested by Gerrard et al while studying allergic disease in the Metis Indian community in Canada.2 Strachan refined this observation from large UK cohorts, in which he found an inverse relation between the number of older siblings and the prevalence of hay fever, but not asthma.3 He emphasised that the link was through atopy to allergic disease. Several studies have subsequently shown reduced asthma prevalence in school-aged children with early daycare attendance. These children tend to show more early wheezing, but less asthma later on. The proposed explanation is that they contract more upper respiratory tract infections from close contact with children, and this leads them to have more early wheezing, but, in turn, protects them from later developing atopy and atopic disease. This explanation seems less likely in the study by Robertson et al, given that the prevalence of hay fever and eczema increased while asthma prevalence decreased. However, one would need to know the atopic status of the children to clarify the issue. The 26% reduction in current wheeze prevalence in Melbourne, while significant, is within the range found in Australia in phase 1 of the International Study of Asthma and Allergies in Childhood (ISAAC) study. For example, in the four Australian centres that took part, there was a 19% difference between the highest and lowest prevalence. For sleep disturbance and speech limitation, this was 40%.4 There is even greater variation in large cities. In Mumbai (Bombay), for example, reported current wheeze varied by more than 100% in different parts of the city. Large cities are not homogeneous, with large variations in many factors that may affect wheezing, such as housing conditions, smoking prevalence, diet and variable access to healthcare. Over time, with gentrification and changes in zoning, factors may vary even in the same narrow geographic location. Robertson et al also note that awareness of asthma in the community is a determinant of the prevalence of reported symptoms. The pool of individuals with a history of symptoms in any population will be larger than the proportion who report symptoms in a defined period. In a resurvey of 700 young adults, all of whom had 4 years previously responded positively to at least one of three asthma questions, only two-thirds reported symptoms. In the first survey, 28% had responded positively to all three questions, and in the second, 29%. However, only 60% were the same individuals.5 Just how large this pool is has recently been clarified, at least in New Zealand. In a 26-year follow-up of a birth cohort in Dunedin, 73% reported wheezing on at least one occasion and 51% on at least two.6 Given that there is likely to be some loss to recall, wheezing at some time between birth and adulthood appears virtually universal. Clearly, most of this wheezing is occasional, trivial, inconsequential, and a normal phenomenon. It is now easy to see how a change in diagnostic and hence societal emphasis on wheezing, as opposed to bronchitis, with attendant changes in treatment, can enhance recall for asthma in cross-sectional surveys. Perhaps this emphasis is now stabilising and the diagnostic label “asthma” is being applied slightly less frequently in Melbourne. The strengths of the ISAAC approach — simple questionnaires requiring minimal funding — allow large-scale international comparisons of children (in fact, this is the only way that such large population studies can be conducted), but interpreting relatively small changes over time in a very asthma-“savvy” environment like Australia is more difficult. Although the ISAAC approach clearly shows that reported asthma symptoms are far more frequent in Australia, New Zealand and the United Kingdom compared with, say, Albania or India (more than 10-fold), smaller differences over relatively short time intervals in individual countries are harder to interpret. In the past 30 years there have been many cross-sectional studies reporting an increase in the prevalence of asthma symptoms over time. In only two has this been accompanied by measures of airway hyperresponsiveness. In the first, in the United Kingdom, Burr et al showed that current asthma symptom reporting had doubled over a 15-year period, but exercise-induced fall in peak expiratory flow rate had not changed.7 In the second, Peat et al showed a doubling of current symptoms and airway hyperresponsiveness, predominantly among atopic children, suggesting an increase in asthma relating to greater allergen exposure.8 There is a real need for the measurement of objective markers over time in similar populations. The advent of easily obtainable markers of airway inflammation, such as exhaled nitric oxide or constituents of breath condensate, may allow population studies of airway inflammation to be quantified and tracked over time. Perhaps it is time to abandon our inconvenient population model of asthma as a disease, just as doctors did for essential hypertension in the 1950s.9 Nature provides no obvious support for asthma and we can neither define nor measure it accurately; indeed, it remains a mystery because it is largely an illusion. The late Geoffrey Rose (Professor of Epidemiology at the London School of Hygiene and Tropical Medicine) suggested that we should seek the answers to “disease” by exploring populations rather than atypical minorities.10 We need to consider applying this concept to airway inflammation. Now that appropriate tools are becoming available, we should measure airway inflammation and airway responses in large populations and explore the environmental and genetic factors that affect the airway at a population level. This might reveal that it is not just the upper end of the distribution of airway inflammation (which we arbitrarily and inconsistently call asthma) that varies by environment, and over time, but the whole distribution. In the meantime, Robertson and colleagues have shown that parent-reported asthma symptoms of young Melbourne children have declined in the past decade. This may or may not be an early signal for a real decline in asthma prevalence. What it does suggest is that asthma prevalence has not increased, which in itself is a welcome observation.

Julian Crane MB BS, FRCP, FRACP

All women and men with a history of fragility fractures should be considered for treatment of osteoporosis to reduce their risk of future fracture. There is high-level evidence for the anti-fracture efficacy of treatment in women with osteoporosis, particularly if there is prevalent fracture; the evidence is less compelling for women with osteopenia, with or without a fracture, and for men. The rigorously investigated drugs reported to reduce vertebral fractures are the bisphosphonates alendronate and risedronate, the selective oestrogen-receptor modulator raloxifene, the anabolic agent parathyroid hormone and, most recently, strontium ranelate. Only the two bisphosphonates and hormone replacement therapy (HRT) have been reported to reduce hip fractures in community-dwelling women, and calcium plus vitamin D and hip protectors have been reported to reduce these fractures in elderly people in institutions. HRT is not recommended in women for fracture risk reduction alone. Evidence for the anti-fracture efficacy of calcitonin, fluoride, anabolic steroids and active vitamin D metabolites is insufficient to justify their use; lifestyle changes, while not shown to reduce fracture risk, may have a role in maintaining bone strength throughout life.

Ego Seeman BSc, FRACP, MD · John A Eisman FRACP, PhD

Osteoarthritis is a common, chronic condition which requires an individualised management plan involving multiple kinds of treatment. Exercise programs and the Arthritis Self-Management Program reduce pain and disability associated with osteoarthritis. Paracetamol is the most appropriate first-line analgesic. Non-steroidal anti-inflammatory drugs may be used as second-line analgesia on an as-needed basis (including continuous use), but must be used with caution. Cyclo-oxygenase-2-specific inhibitors are used if there are risk factors for upper-gastrointestinal complications, but only after considering cardiovascular risk. Glucosamine sulfate is a safe and effective over-the-counter treatment. Intra-articular therapies are used when others have failed.

Rebecca Grainger MB ChB (Distinction) · Flavia M Cicuttini FRACP, PhD

Objective: To determine the clinical significance of definite bites by mouse spiders (Actinopodidae: Missulena spp.) from published case reports/series and museum records.Data sources: A computerised literature search of MEDLINE and EMBASE was undertaken. All cases reported to major Australian museums and reports from venom researchers working with mouse spiders were also reviewed. Textbooks on clinical toxinology were searched and further reports of cases were located.Study selection: All cases of definite spider bites where the spider was collected and identified by an expert as a mouse spider were included.Data extraction: All reports were evaluated and the following data extracted: patient demographics (age, sex, geographical location, season), bite site, local and systemic effects, and hospital attendance. Clinical effects were classified into three groups: severe neurotoxic envenoming, local neurotoxic effects or mild systemic effects, and minor local effects.Data synthesis: Forty definite bites were identified from around Australia, with only one case of severe envenoming (a 19-month-old child). Local neurotoxic effects occurred in six cases and minor systemic effects in five. There was no evidence of envenoming in most bite victims, and the rate of severe envenoming was 2.5% (95% CI, 0–13%). There were no recorded deaths.Conclusions: In most cases, bites by mouse spiders cause only minor or moderate effects. Severe envenoming is rare and far less common than for funnel-web spider bites. Mouse spider bites do not appear to be a major medical problem.

Geoffrey K Isbister MB BS, BSc, FACEM

Objective: To assess if there are any differences in statin prescribing across Australia by socioeconomic status or sex and to relate prescribing rates to coronary heart disease (CHD) mortality rates.Design: Cross-sectional study using data on statin prescribing by age, sex and patient postcode for the period May to December 2002.Setting and participants: The Australian population, stratified by sex and quintile of Index of Relative Socio-Economic Disadvantage (IRSD).Main outcome measures: Age-standardised rates of statin scripts per 1000 population per month for each sex and IRSD quintile.Results: 9.1 million prescriptions for statins were supplied between May and December 2002, for a total cost of $570 million. The age-standardised rates for statin prescribing in women varied from 56.9 (95% CI, 56.6–57.2) scripts per 1000 population per month in the most disadvantaged socioeconomic quintile through 53.4 (95% CI, 53.0–53.7), 50.3 (95% CI, 50.0–50.6), 48.4 (95% CI, 48.1–48.7) to 46.3 (95% CI, 46.0–46.6) in the least disadvantaged quintile. For men the figures were 52.6 (95% CI, 52.3–52.9), 50.9 (95% CI, 50.6–51.2), 48.8 (95% CI, 48.6–49.1), 47.7 (95% CI, 47.4–47.9), and 51.9 (95% CI, 51.6–52.2). There was a significant linear association between statin prescribing and CHD mortality by quintile of socioeconomic disadvantage in women (weighted least squares slope, 0.380; 95% CI, 0.366 to 0.395; P < 0.0001), but not in men (slope, − 0.002; 95% CI, − 0.010 to 0.006; P = 0.65).Conclusions: Our results suggest that in men there is either overprescribing of statins in the highest socioeconomic quintile or underprescribing in the lowest. Furthermore, contrary to expectation, women — relative to men — are prescribed statins at higher rates at lower levels of risk (using CHD deaths as a proxy measure of risk).

Nigel P Stocks MD · Heather McElroy DipStats · Philip Ryan MB BS · James Allan MB BS

Joint replacement is the most effective healthcare measure in improving patient quality-of-life outcomes. More than 46 000 hip and knee replacements were performed in Australia between July 2000 and July 2001. The need for joint replacements will increase as the population ages. More than 90% of hip and/or knee replacements survive for 10–15 years. Prosthesis selection needs to be tailored to each patient, although rationalisation ...

John A L Hart FRACS, FAOrthA, FACSP(Hon)

Neil H Cradick General Practitioner, PO Box 1127, Buderim, QLD 4556. cradwhitAToptusnet.com.au To the Editor: On opening the MJA Focus document “Prevention of cardiovascular disease: an evidence-based clinical aid”,1 I expected to find useful and contemporary guidelines for general practice. However, I was surprised to read two of the recommendations — for the use of antihypertensive and antiplatelet drugs in “low risk” patients (those without risk-associated clinical conditions or end-organ damage). The document recommends drug treatment only if systolic blood pressure is > 180 mmHg or diastolic blood pressure is > 100 mmHg in people under 60 years, or systolic blood pressure is > 160 mmHg in people over 60 years. While Fulcher et al1 volunteered that this was at odds with clinical practice, they supported the recommendations by stating that they were in accordance with published guidelines. The data for these conservative hypertension parameters were published nearly 10 years ago,2 or derived from textbooks,3 and are at odds with the 1999 WHO/ISH guidelines,4 and even more at odds with the excellent Joint National Committee (JNC 7) report.5 The latter publication recommends, after lifestyle recommendations, drug treatment for a blood pressure of 140–159/90–99 mmHg for those without end-organ damage. Furthermore, the focus document recommends primary prevention with aspirin in those with a calculated annual cardiovascular event risk > 3%. Hayden et al6 suggest antiplatelet treatment should be offered to those with a 5-year cardiovascular event risk > 3%, which equates to a > 0.6% annual risk. The benefit to harm ratio needs to be explained to the individual, and therapy should only be initiated once blood pressure is controlled. As an interested general practitioner and user of evidence-based guidelines, I usually check the funding of publications, and, with the heavy emphasis on the use of ACE inhibitors (in particular ramipril) and statins (which are produced by Aventis Pharma), it is difficult to rely on the evidence as presented. I would hope that independent bodies such as the National Prescribing Service or Australian Prescriber could take the pharmaceutical lead and produce desktop references with a more unbiased opinion on the latest collection of evidence that is shaking us up in primary care medicine. I would again refer readers to the excellent hypertension guidelines mentioned above4,5 (in particular the JNC 7 reference card available on the Internet at www.nhlbi.nih.gov/guidelines/hypertension/jnc7card.htm), and caution them to remain wary of easy-reference desktop items funded by pharmaceutical companies.

Neil H Cradick

Caroline M de Costa Obstetrician and Gynaecologist, Cairns Base Hospital, Cairns, QLD 4870. carolinedecAThotkey.net.au To the Editor: As a “grand multip” myself, I turned with interest to Humphrey’s recently published study of grand multiparity and pregnancy risk at Cairns Base Hospital.1 However, I cannot support his conclusions. Throughout the period of the study, most grand multiparous women giving birth at this hospital were actively managed in the third stage of labour with a regimen designed to prevent postpartum haemorrhage (intravenous ergometrine/oxytocin). Women of lesser parity were also given preventive therapy, but generally in lower doses and less consistently. This is a major confounding factor not addressed in Humphrey’s study. Clearly, an unknown, but probably significant, number of haemorrhages were prevented by this treatment. Given that 9.2% of grand multiparous women still had a postpartum haemorrhage, any prospective randomised controlled trial that allowed some of these women not to have active management of the third stage would be unethical. Numerous other studies have shown an association between grand multiparity and postpartum haemorrhage. 2-4 These include the study of Babinszki and colleagues, which limited study subjects to upper-class, private patients and thereby eliminated many confounding variables.4 Humphrey’s study does not report the severity of the postpartum haemorrhages that did occur; even a small number of life-threatening haemorrhages could justify continuing very active preventive measures in grand multiparous women. The incidences of anaemia and previous postpartum haemorrhage, not recorded in the study, would also be of interest; both are independent reasons to actively manage the third stage in women of any parity, and there are good reasons to believe that both may be more common in grand multiparous women. Humphrey also states that grand multiparous women did not have higher perinatal mortality rates or poorer maternal outcomes than women of lower parity. However, whenever possible throughout the period of the study, grand multiparous women were identified on booking into antenatal care and treated by senior obstetricians. Many had conditions such as diabetes, hypertension, anaemia and heart disease managed carefully to ensure as good a pregnancy outcome as possible. This focused obstetric care could well have counteracted any natural tendency of grand multiparous women towards poorer outcomes, and thus it is not possible to draw any conclusions about perinatal results from the data provided. What is clear from these data is that grand multiparous women in far north Queensland are often economically and socially disadvantaged compared with women of lower parity. This is a common finding in almost all studies of grand multiparity. 2,3,5 We should remember that these women are taking home a new baby to conditions that may already be quite compromised. They deserve the best obstetric care we can offer them, and we should be very cautious when reviewing protocols that we do not increase risks to these women or their babies.

Caroline M de Costa