Cautionary tales in the interpretation of systematic reviews of therapy trials

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Heparin-induced thrombocytopenia: recent experience in a large teaching hospital

Background: Heparin-induced thrombocytopenia (HIT) is a potentially serious adverse reaction caused by platelet-activating antibodies. Aim: To describe experience with HIT. Methods: Twenty-two patients identified by laboratory records of heparin-associated antibodies with a 50% or greater decrease in platelet count were reviewed in our 600-bed metropolitan teaching hospital from 1999 to April 2005. Results: There was an increase in the frequency of HIT diagnosed during the review period, which was associated with a rise in the number of requests for HIT antibodies. Thrombotic complications were identified in 14 of 22 patients with HIT. Mean age was 65 years, and 11 patients were men. Seven patients died and HIT was considered contributory in four. One patient required mid-forearm amputation. Unfractionated heparin was used in all cases and five patients also received enoxaparin. Mean time to HIT screen, reflecting when the diagnosis was first suspected, was 14 days. Platelet nadir ranged from 6 x 10(9)/L to 88 x 10(9)/L, with a percentage drop in platelet count of 67-96%. Alternative anticoagulation (danaparoid) was not used in three patients, two of whom died. Conclusions: HIT is a potentially life-threatening complication of heparin therapy, associated with a fall in platelet count and a high incidence of thromboembolic complications. It is most frequently seen using unfractionated heparin therapy. The increase in frequency of HIT diagnosed in our hospital appears to be associated with a greater awareness of the entity, although detection is often delayed. Platelet count should be monitored in patients on heparin and the presence of antiplatelet antibodies determined if HIT is suspected. Treatment involves both discontinuation of heparin and the use of an alternative anticoagulant such as danaparoid because of the persisting risk of thrombosis.

The mental health risks of adolescent cannabis use

Since the early 1970s, when cannabis first began to be widely used [1], the proportion of young people who have used cannabis has steeply increased and the age of first use has declined [2, 3]. Most cannabis users now start in the mid-to-late teens [1], an important period of psychosocial transition when misadventures can have large adverse effects on a young person's life chances.

Health system reform in Mexico 5: Assessing the effect of the 2001-06 Mexican health reform: an interim report card

Since 2001, Mexico has been designing, legislating, and implementing a major health-system reform. A key component was the creation of Seguro Popular, which is intended to expand insurance coverage over 7 years to uninsured people, nearly half the total population at the start of 2001. The reform included five actions: legislation of entitlement per family affiliated which, with full implementation, will increase public spending on health by 0.8-1.0% of gross domestic product; creation of explicit benefits packages; allocation of monies to decentralised state ministries of health in proportion to number of families affiliated; division of federal resources flowing to states into separate funds for personal and non-personal health services; and creation of a fund to protect families against catastrophic health expenditures. Using the WHO health-systems framework, we used a wide range of datasets to assess the effect of this reform on different dimensions of the health system. Key findings include: affiliation is preferentially reaching the poor and the marginalised communities; federal non-social security expenditure in real per-head terms increased by 38% from 2000 to 2005; equity of public-health expenditure across states improved; Seguro Popular affiliates used more inpatient and outpatient services than uninsured people; effective coverage of 11 interventions has improved between 2000 and 2005-06; inequalities in effective coverage across states and wealth deciles has decreased over this period; catastrophic expenditures for Seguro Popular affiliates are lower than for uninsured people even though use of services has increased. We present some lessons for Mexico based on this interim evaluation and explore implications for other countries considering health reforms.

The role of BNP testing in heart failure

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.

Methicillin-resistant Staphylococcus aureus in the Australian community: an evolving epidemic

Objective: To describe antimicrobial resistance and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolated in community settings in Australia. Design and setting: Survey of S. aureus isolates collected prospectively Australia-wide between July 2004 and February 2005; results were compared with those of similar surveys conducted in 2000 and 2002. Main outcome measures: Up to 100 consecutive, unique clinical isolates of S. aureus from outpatient settings were collected at each of 22 teaching hospital and five private laboratories from cities in all Australian states and territories. They were characterised by antimicrobial susceptibilities (by agar dilution methods), coagulase gene typing, pulsed-field gel electrophoresis, multilocus sequence typing, SCCmec typing and polymerase chain reaction tests for Panton-Valentine leukocidin (PVL) gene. Results: 2652 S. aureus isolates were collected, of which 395 (14.9%) were MRSA. The number of community-associated MRSA (CA-MRSA) isolates rose from 4.7% (118/2498) of S. aureus isolates in 2000 to 7.3% (194/2652) in 2004 (P=0.001). Of the three major CA-MRSA strains, WA-1 constituted 45/257 (18%) of MRSA in 2000 and 64/395 (16%) in 2004 (P=0.89), while the Queensland (OLD) strain increased from 13/257 (5%) to 58/395 (15%) (P=0.0004), and the south-west Pacific (SWP) strain decreased from 33/257 (13%) to 26/395 (7%) (P=0.01). PVL genes were detected in 90/195 (46%) of CA-MRSA strains, including 5/64 (8%) of WA-1, 56/58 (97%) of OLD, and 25/26 (96%) of SWP strains. Among health care-associated MRSA strains, all AUS-2 and AUS-3 isolates were multidrug-resistant, and UK EMRSA-15 isolates were resistant to ciprofloxacin and erythromycin (50%) or to ciprofloxacin alone (44%). Almost all (98%) of CA-MRSA strains were non-multiresistant. Conclusions: Community-onset MRSA continues to spread throughout Australia. The hypervirulence determinant PVL is often found in two of the most common CA-MRSA strains. The rapid changes in prevalence emphasise the importance of ongoing surveillance.

Does being against euthanasia legislation equate to being anti-euthanasia?

This study investigated issues raised in qualitative data from our previous studies of health professionals and community members, which suggested that being opposed to euthanasia legislation did not necessarily equate to being anti-euthanasia per se. A postal survey of 1002 medical practitioners, 1000 nurses and 1200 community members was undertaken. In addition to a direct question on changing the law to allow active voluntary euthanasia (AVE), four statements assessed attitudes to euthanasia with or without a change in legislation. Responses were received from 405 doctors (43%), 429 nurses (45%) and 405 community members (38%). Compared with previous studies there was a slight increase in support for a change in the law from medical practitioners, a slight decrease in support from community members and almost no change among nurses. Different interpretations of the results of the four attitude questions are possible, depending on the perspective of the interpreter.

Predictors of an antibiotic prescription by GPs for respiratory tract infections: a pilot

Background. Antibiotics are over-prescribed for respiratory tract infections in Australia. Objectives. The aim of this study was to describe the clinical predictors of GPs' prescribing of antibiotics. Methods. We used Clinical Judgment Analysis to study the responses of GPs to hypothetical paper-based vignettes of a 20-year-old with a respiratory tract infection. The nature of four symptoms and signs (colour of nasal mucous discharge; soreness of the throat; presence of fever; and whether any cough was productive of sputum) was varied and their effect on prescribing measured using logistic regression. Results. Twenty GPs participated. The nature of each symptom and sign significantly predicted prescribing of an antibiotic. Cough productive of yellow sputum; presence of sore throat; fever; and coloured nasal mucus increased the probability of an antibiotic being prescribed. Conclusions. GPs are influenced by clinical signs and symptoms to use antibiotics for respiratory infections for which there is poor evidence of efficacy from the literature.