Otitis media (OM) continues to be one of the most common childhood infections and is a major cause of morbidity in children. The pathogenesis of OM is multifactorial, involving the adaptive and native immune system, Eustachian-tube dysfunction, viral and bacterial load, and genetic and environmental factors. Initial observation seems to be suitable for many children with OM, but only if appropriate follow-up can be assured. In children younger than 2 years with a certain diagnosis of acute OM, antibiotics are advised. Surgical candidacy depends on associated symptoms, the child's developmental risk, and the anticipated chance of timely spontaneous resolution of the effusion. The recommended approach for surgery is to start with tympanostomy tube placement, eventually followed by adenoidectomy. The ideal intervention for OM, however, does not yet exist, and an urgent need remains to explore new and creative options based on modern insights into the pathophysiology of OM.

This review summarises the psychiatry of the puerperium, in the light of publications during the past 5 years. A wide variety of disorders are seen. Recognition of disorders of the mother-infant relationship is important, because these have pernicious long-term effects but generally respond to treatment. Psychoses complicate about one in 1000 deliveries. The most common is related to manic depression, in which neuroleptic drugs should be used with caution. Post-traumatic stress disorder, obsessions of child harm, and a range of anxiety disorders all require specific psychological treatments. Postpartum depression necessitates thorough exploration. Cessation of breastfeeding is not necessary, because most antidepressant drugs seem not to affect the infant. Controlled trials have shown the benefit of involving the child's father in therapy and of interventions promoting interaction between mother and infant. Owing to its complexity, multidisciplinary specialist teams have an important place in postpartum psychiatry.

Many oncologists believe that patients with cancer who enroll in clinical trials have better outcomes than those who do not enroll. We aimed to assess the empirical evidence that such a trial effect exists.

Intestinal infection with Vibrio cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Cholera toxin, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity. Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V cholerae serogroup O1, biotype El Tor, has moved from Asia to cause pandemic disease in Africa and South America during the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. Research on case management of cholera led to the development of rehydration therapy for dehydrating diarrhoea in general, including the proper use of intravenous and oral rehydration solutions. Appropriate case management has reduced deaths from diarrhoeal disease by an estimated 3 million per year compared with 20 years ago. Vaccination was thought to have no role for cholera, but new oral vaccines are showing great promise.

A WHO expert consultation addressed the debate about interpretation of recommended body-mass index (BMI) cut-off points for determining overweight and obesity in Asian populations, and considered whether population-specific cut-off points for BMI are necessary. They reviewed scientific evidence that suggests that Asian populations have different associations between BMI, percentage of body fat, and health risks than do European populations. The consultation concluded that the proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMIs lower than the existing WHO cut-off point for overweight (> or =25 kg/m2). However, available data do not necessarily indicate a clear BMI cut-off point for all Asians for overweight or obesity. The cut-off point for observed risk varies from 22 kg/m2 to 25 kg/m2 in different Asian populations; for high risk it varies from 26 kg/m2 to 31 kg/m2. No attempt was made, therefore, to redefine cut-off points for each population separately. The consultation also agreed that the WHO BMI cut-off points should be retained as international classifications. The consultation identified further potential public health action points (23.0, 27.5, 32.5, and 37.5 kg/m2) along the continuum of BMI, and proposed methods by which countries could make decisions about the definitions of increased risk for their population.

Large gains in the reduction of malaria mortality in the early 20th century were lost in subsequent decades. Malaria now kills 2-3 million people yearly. Implementation of malaria control technologies such as insecticide-treated bednets and chemotherapy could reduce mortality substantially, but an effective malaria vaccine is also needed. Advances in vaccine technology and immunology are being used to develop malaria subunit vaccines. Novel approaches that might yield effective vaccines for other diseases are being evaluated first in malaria. We describe progress in malaria vaccine development in the past 5 years: reasons for cautious optimism, the type of vaccine that might realistically be expected, and how the process could be hastened. Although exact predictions are not possible, if sufficient funding were mobilised, a deployable, effective malaria vaccine is a realistic medium-term to long-term goal.

Despite improvements in health care, the incidence of infective endocarditis has not decreased over the past decades. This apparent paradox is explained by a progressive evolution in risk factors; while classic predisposing conditions such as rheumatic heart disease have been all but eradicated, new risk factors for infective endocarditis have emerged. These include intravenous drug use, sclerotic valve disease in elderly patients, use of prosthetic valves, and nosocomial disease. Newly identified pathogens, which are difficult to cultivate--eg, Bartonella spp and Tropheryma whipplei--are present in selected individuals, and resistant organisms are challenging conventional antimicrobial therapy. Keeping up with these changes depends on a comprehensive approach, allying understanding of the pathogenesis of disease with the development of new drugs for infective endocarditis. Infection by staphylococci and streptococci is being dissected at the molecular level. New ideas for antimicrobial agents are being developed. These novel insights should help redefine preventive and therapeutic strategies against infective endocarditis.

Although little is known as yet about the processes that coordinate cell-signalling pathways, matrix proteins are probably major players in this type of global control. The CCN (cyr61, ctgf, nov) proteins are an important family of matricellular regulatory factors involved in internal and external cell signalling. This family participates in angiogenesis, chondrogenesis, and osteogenesis, and they are probably involved in the control of cell proliferation and differentiation.

Nosologically, transmissible spongiform encephalopathies (TSE or prion diseases) should be grouped with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, which are all caused by toxic gain of function of an aberrant form of a constitutively expressed protein. Failure to clear these proteins from the brain induces neuronal dysfunction. Transmissibility is the property that separates TSE from other neurodegenerative diseases, and this property seems to reside within the structure of the abnormal protein. The human phenotypic range of these encephalopathies includes Creutzfeldt-Jakob disease and its variant form, kuru, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Notwithstanding the generally low incidence of TSE and their limited infectiousness, major epidemics such as bovine spongiform encephalopathy and kuru arise in situations where intraspecies recycling of the abnormal protein is sustained. Moreover, evidence of chronic subclinical infection in animals offers insights into pathogenesis and prompts re-evaluation of the notion of species barriers and present infection control measures. Since case-to-case transmission is the only known mechanism underlying epidemics of TSE, potential reservoirs of infectivity in the tails of epidemics need continued vigilance.

More than 170 million people worldwide are chronically infected with the hepatitis C virus (HCV), which is responsible for more than 100000 cases of liver cancer per year, with similar numbers of digestive haemorrhage and ascites episodes. Major breakthroughs have been made in diagnosis and treatment, and advances in molecular biology mean that the replicative state of the virus can now be assessed. Genotype and serum viral load are useful predictors of response to treatment. The combination of pegylated interferon and ribavirin can eradicate the virus in more than 50% of patients. These antiviral treatments reduce liver fibrosis progression and can reverse cirrhosis. Unfortunately, even in developed countries, death due to hepatitis C is increasing because of inadequate detection and treatment.

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.

A world torn by gross health inequalities is in serious trouble. The global health community can do much to reduce suffering and death among vulnerable groups. WHO is changing its way of working, alongside member states and financial and technical partners, to reach key national health goals and strengthen equity. The most urgent objectives include the health-related Millennium Development Goals, the 3 by 5 target in HIV/AIDS treatment (to provide 3 million people in developing regions with access to antiretroviral treatment by the end of 2005), and addressing the growing epidemics of non-communicable diseases. The key to achieving these objectives is strengthening of health systems guided by the values of Health For All.

Crohn's disease is the result of an abnormal immune response of the gut mucosa triggered by one or more environmental risk factors in people with predisposing gene variations, including CARD15 mutations. Epidemiological data allow assessment of familial environmental risk factors related to western lifestyle, diet, bacteria, and domestic hygiene. All findings point to refrigeration as a potential risk factor for Crohn's disease. Furthermore, cold-chain development paralleled the outbreak of Crohn's disease during the 20th century. The cold chain hypothesis suggests that psychrotrophic bacteria such as Yersinia spp and Listeria spp contribute to the disease. These bacteria have been identified in Crohn's disease lesions and we discuss their pathogenic properties with respect to our knowledge of the disease. From a molecular perspective, we postulate that the disease is a result of a defect in host recognition by pathogenic bacterial components that usually escape the immune response (eg, Yop molecules), which results in an excessive host response to these bacteria.

Drug-resistant HIV-1 is a cause of growing clinical and public-health concern. In many patients, combination antiretroviral therapy fails to achieve complete viral suppression (virological failure). Continuing viral replication during therapy leads to the accumulation of drug-resistance mutations, resulting in increased viral load and a greater risk of disease progression. Patients with drug-resistant HIV-1 infection have three therapeutic options: a change to a salvage regimen with the aim of fully suppressing viral replication; interruption of therapy; or continuation of a partially effective regimen. The first strategy is preferred for most patients failing their first or perhaps their second regimen. However, the best approach remains unclear for patients who have failed multiple treatment regimens and who have limited options for complete viral suppression. The management of such patients requires a careful understanding of the pathogenesis of drug-resistant HIV-1, the clinical consequences of virological failure, the potential benefits and limitations of diagnostic assays, and the likelihood that agents in development will be effective.

This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.

Surgical injury can be followed by pain, nausea, vomiting and ileus, stress-induced catabolism, impaired pulmonary function, increased cardiac demands, and risk of thromboembolism. These problems can lead to complications, need for treatment in hospital, postoperative fatigue, and delayed convalescence. Development of safe and short-acting anaesthetics, improved pain relief by early intervention with multimodal analgesia, and stress reduction by regional anaesthetic techniques, beta-blockade, or glucocorticoids have provided important possibilities for enhanced recovery. When these techniques are combined with a change in perioperative care a pronounced enhancement of recovery and decrease in hospital stay can be achieved, even in major operations. The anaesthetist has an important role in facilitating early postoperative recovery by provision of minimally-invasive anaesthesia and pain relief, and by collaborating with surgeons, surgical nurses, and physiotherapists to reduce risk and pain.

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C virus infection. Patients with cirrhosis are at the highest risk and should be monitored every 6 months. Surveillance can lead to diagnosis at early stages, when the tumour might be curable by resection, liver transplantation, or percutaneous treatment. In the West and Japan, these treatments can be applied to 30% of patients, and result in 5-year survival rates higher than 50%. Resection is indicated among patients who have one tumour and well-preserved liver function. Liver transplantation benefits patients who have decompensated cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm, but donor shortage greatly limits its applicability. This difficulty might be overcome by living donation. Most HCC patients are diagnosed at advanced stages and receive palliative treatments, which have been assessed in the setting of 63 randomised controlled trials during the past 25 years. Meta-analysis shows that only chemoembolisation improves survival in well-selected patients with unresectable HCC.

In recent years, several risk factors for adverse outcome in patients undergoing anaesthesia have been identified. Besides human errors, cardiovascular and respiratory complications are associated with substantial morbidity. Assessment of complications has promoted the introduction of basic physiological monitoring in clinical practice. Whether monitoring directly affects outcome is not proven; however, circumstantial evidence suggests that basic cardiorespiratory monitoring decreases the incidence of serious accidents. Prevention of hypothermia also reduces anaesthesia-related morbidity. Measurement of body temperature is mandatory, and active warming is a simple, effective technique to avoid hypothermia. Evidence is growing that patients with known or suspected coronary artery disease should be treated with beta blockers perioperatively. Whether the type of anaesthesia-ie, general or regional-is relevant to perioperative mortality remains unclear. In subgroups of patients at high risk, neuraxial anaesthesia reduces the rate of respiratory and cardiovascular complications.