Epilepsy is the most common serious neurological disorder affecting an estimated 50 million people worldwide. Particular focus should be placed on a safe diagnosis, seizure and syndrome classification, and choice of pharmacological and surgical options for a range of patient populations with different health-care requirements. Eight new antiepileptic drugs were licensed in the 1990s with more to come. These new drugs along with earlier resective surgery have led to a better outcome for many more people with this condition.

Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected patients. With the sustained major declines in opportunistic complications, HIV infection is a more chronic disease, and so more drugs are being used in more patients for longer periods. This review focuses on the pathogenesis, clinical features, and management of the principal toxicities of the 15 licensed antiretroviral drugs, including mitochondrial toxicity, hypersensitivity, and lipodystrophy, as well as more drug-specific adverse effects and special clinical settings.

Concern about upper-genital-tract infection related to intrauterine devices (IUDs) limits their wider use. In this systematic review I summarise the evidence concerning IUD-associated infection and infertility. Choice of an inappropriate comparison group, overdiagnosis of salpingitis in IUD users, and inability to control for the confounding effects of sexual behaviour have exaggerated the apparent risk. Women with symptomless gonorrhoea or chlamydial infection having an IUD inserted have a higher risk of salpingitis than do uninfected women having an IUD inserted; however, the risk appears similar to that of infected women not having an IUD inserted. A cohort study of HIV-positive women using a copper IUD suggests that there is no significant increase in the risk of complications or viral shedding. Similarly, fair evidence indicates no important effect of IUD use on tubal infertility. Contemporary IUDs rival tubal sterilisation in efficacy and are much safer than previously thought.

The effectiveness of surgery for colorectal cancer depends on it being carried out safely, which allows most patients to return to productive lives, with an improved postoperative life expectancy, or at least one that is not diminished by the surgery. Because colorectal cancer is a major cause of morbidity and mortality in elderly people, we have examined how the outcomes of surgery in elderly patients differ from those in younger patients.

The advent of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) has revolutionised the treatment of hypercholesterolaemia. Statin treatment, by lowering the atherogenic lipoprotein profile, reduces morbidity and mortality in patients with cardiovascular disease. Treatment with simvastatin causes a reduction of events of new-onset heart failure, but this may be attributable to properties other than its lipid-lowering effects. There is some evidence that lower serum cholesterol concentrations (as a surrogate for the totality of lipoproteins) relate to impaired survival in patients with chronic heart failure (CHF). Inflammation is a feature in patients with CHF and increased lipopolysaccharide may contribute substantially. We postulate that higher concentrations of total cholesterol are beneficial in these patients. This is potentially attributable to the property of lipoproteins to bind lipopolysaccharide, thereby preventing its detrimental effects. We hypothesise there is an optimum lipoprotein concentration below which lipid reduction would, on balance, be detrimental. We also propose that, in patients with CHF, a non-lipid-lowering statin (with ancillary properties such as immune modulatory and anti-inflammatory actions) could be as effective or even more beneficial than a lipid-lowering statin.

The decrease in mortality and improved outcome for patients with severe traumatic brain injury over the past 25 years can be attributed to the approach of "squeezing oxygenated blood through a swollen brain". Quantification of cerebral perfusion by monitoring of intracranial pressure and treatment of cerebral hypoperfusion decrease secondary injury. Before the patient reaches hospital, an organised trauma system that allows rapid resuscitation and transport directly to an experienced trauma centre significantly lowers mortality and morbidity. Only the education of medical personnel and the institution of trauma hospital systems can achieve further improvements in outcome for patients with traumatic brain injuries.

Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder.

Poverty not only excludes people from the benefits of health-care systems but also restricts them from participating in decisions that affect their health. The resulting health inequalities are well documented, and the search for greater equity attracts many concerned players and initiatives. Fundamental to the success of these efforts, however, is the need for people to be able to negotiate their own inclusion into health systems and demand adequate health care. This calls for a restatement of the centrality of people in public health and its practice. New forms of communication and cooperation are required at all levels of society, nationally, and internationally, to ensure equitable exchange of views and knowledge to formulate appropriate action to redress inequalities and improve people's health and wellbeing.

There is widespread belief that individuals who were physically abused during childhood are more likely to abuse their own children than those who were not abused, but the empirical studies examining this belief have not been systematically reviewed. The aim of this study was to evaluate systematically, based on eight methodological standards derived from a hypothetical randomised controlled trial, the design of studies investigating the intergenerational transmission of child physical abuse.

Air pollution contributes to mortality and morbidity. We estimated the impact of outdoor (total) and traffic-related air pollution on public health in Austria, France, and Switzerland. Attributable cases of morbidity and mortality were estimated.

Current diagnostic tests for tuberculosis based on tuberculin have poor specificity, and both BCG vaccination and exposure to non-tuberculosis mycobacteria produce a response similar to that induced by infection with Mycobacterium tuberculosis. The identification of regions of the M. tuberculosis genome that are not present in BCG and non-tuberculous mycobacteria provides a unique opportunity to develop new highly specific diagnostic reagents. We describe the current status of attempts to exploit this information and summarise recent research that has used defined antigens for an accurate and rapid test for tuberculosis infection based on the detection of T cells sensitised to M. tuberculosis either by blood tests in vitro or skin tests in vivo.

Although thrombolytic therapy given by bolus injection seems to be as effective as infusion over 60-90 min, no single trial has been adequately powered to detect clinically important safety differences between the two strategies. We did a meta-analysis to find out whether bolus administration of thrombolytics is associated with an increased frequency of intracranial haemorrhage.

A hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage. Most patients presenting with hypertensive emergency have chronic hypertension, although the disorder can present in previously normotensive individuals, particularly when associated with pre-eclampsia or acute glomerulonephritis. The pathophysiological mechanisms causing acute hypertensive endothelial failure are complex and incompletely understood but probably involve disturbances of the renin-angiotensin-aldosterone system, loss of endogenous vasodilator mechanisms, upregulation of proinflammatory mediators including vascular cell adhesion molecules, and release of local vasoconstrictors such as endothelin 1. Magnetic resonance imaging has demonstrated a characteristic hypertensive posterior leucoencephalopathy syndrome predominantly causing oedema of the white matter of the parietal and occipital lobes; this syndrome is potentially reversible with appropriate prompt treatment. Generally, the therapeutic approach is dictated by the particular presentation and end-organ complications. Parenteral therapy is generally preferred, and strategies include use of sodium nitroprusside, beta-blockers, labetelol, or calcium-channel antagonists, magnesium for pre-eclampsia and eclampsia; and short-term parenteral anticonvulsants for seizures associated with encephalopathy. Novel therapies include the peripheral dopamine-receptor agonist, fenoldapam, and may include endothelin-1 antagonists.

Treatment of advanced colorectal cancer has progressed substantially. However, improvements in response rates have not always translated into significant survival benefits. Doubts have therefore been raised about the usefulness of tumour response as a clinical endpoint.

There is a remarkable lack of reliable information about the determinants of risk of cardiovascular disease (CVD) among patients with chronic renal failure. Indeed, such patients have often been deliberately excluded from randomised trials of treatments of CVD, perhaps because of concerns about drug safety. But the absolute risk of CVD among them may be large, so the potential absolute benefits of treatments may also be large, and may well exceed any increased hazards. Hence, as well as further investigation of the underlying mechanisms of cardiac disease, it would be helpful to have some large-scale randomised trials in a wide range of renal patients of interventions (such as cholesterol-lowering drugs, antihypertensives, aspirin, B-vitamins, and antioxidant vitamins) that are of proven or suspected benefit in other settings. If safe and effective treatments can be identified, and started early in the natural history of renal failure, the exceptionally high risk of CVD experienced by these patients could be decreased before and after end-stage renal failure has occurred.

There is conflicting evidence on the hypothesis that the risk of depression after stroke is influenced by the location of the brain lesion. We undertook a systematic review to examine the hypotheses that depression is more commonly associated with left-hemisphere strokes than with right-hemisphere strokes and with lesions of the left anterior brain than with other regions.

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

Inborn errors of metabolism commonly present around the time of birth. Although most affected babies are born healthy and subsequently deteriorate, some disorders may present at (or shortly after) birth and a few may be detected by antenatal ultrosonography. In many cases, it is important that the diagnosis is made quickly and a strategy to identify those at high risk is proposed. Treatment should not be delayed for a definitive diagnosis.