Diagnosis and treatment of latent tuberculosis infection (LTBI) is a cornerstone of tuberculosis (TB) control in the developed world. In the last century, the tuberculin skin test (TST) was the only means of diagnosing LTBI. ELISpot and whole-blood ELISA, collectively known as interferon-gamma release assays (IGRAs), are promising new tools.
IGRAs are more specific than TST for diagnosis of LTBI as they are not confounded by previous bacille Calmette-Guerin (BCG) vaccination. Assessing IGRA sensitivity in the absence of a gold standard for LTBI is challenging. Studies have therefore used surrogate markers such as active TB and correlation with degree of TB exposure in contact investigations. These studies suggest that sensitivity of ELISpot is higher than TST while whole-blood ELISA has similar sensitivity to TST. Recent longitudinal studies demonstrating the prognostic power of these tests for development of active TB provide definitive evidence that positive IGRA results reflect infection with dormant yet viable bacilli.
Is the prognostic power of IGRAs greater than the TST? What are the false-negative rates in immunocompromised individuals with LTBI at high risk of progressing to active TB?
IGRAs have been incorporated into national guidelines, although their optimal deployment in diagnostic algorithms is evolving. The health economic benefits of utilizing IGRAs are increasingly recognized, partly because their high specificity avoids unnecessary chemoprophylaxis in BCG-vaccinated persons with false-positive TST results.
Current IGRAs are being improved and next-generation tests, with improved sensitivity, could enable the reliable exclusion of LTBI in immunocompromised individuals.
Cardiac imaging is an emerging application of multidetector computed tomography (MDCT). This review summarizes the current capabilities, possible applications, limitations and developments of cardiac CT.
Relevant publications in peer reviewed literature and national and international guidelines are used to discuss important issues in cardiac CT imaging.
There is broad consensus that coronary CT angiography is indicated in patients with an intermediate pre-test probability of coronary artery disease (CAD) when other non-invasive tests have been equivocal. In this context, CT can reliably exclude significant CAD. Cardiac CT also has an established role in the evaluation of bypass grafts and suspected coronary anomalies. Radiation exposure from CT procedures remains a concern, although techniques are now available to reduce the X-ray dosage without significantly compromising the image quality. However, with the current level of knowledge, the cardiac CT examinations are not justified to screen for CAD in asymptomatic individuals. Neither is it considered appropriate in patients with a high pre-test probability of CAD, for whom invasive catheter coronary angiography is usually of more benefit.
The ability to reconstruct the volumetric cardiac CT data set opens up avenues for advanced physiological analyses of the heart. For example, if CT myocardial perfusion assessment becomes a reality, there is potential to revolutionize the practice of MDCT imaging. Research is also ongoing to investigate whether cardiac CT has a role in the appropriate triage of patients with chest pain in the emergency department.
A large number of drug classes have now been reported to provoke angle closure in high-risk individuals. The mechanism of action can be generalized into three main categories: sympathomimetic, parasympatholytic and idiosyndratic reactions.
This review of the ophthalmic literature provides a clinical summary of primary angle-closure glaucoma (PACG) and its management.
External stimuli (pharmacological and environmental) may induce acute, and more often, asymptomatic angle closure, which carries a significant risk of glaucoma.
Whenever in doubt, patients at risk of PACG who are starting on drug therapy known to provoke angle closure or aggravate the condition should be referred for detailed gonioscopic examination of the anterior chamber by an ophthalmologist.
The use of new imaging methods such as anterior segment optical coherence tomography to assess the presence or risk of angle closure is gaining popularity, and may offer a more rapid method of identifying people who are at risk of sight loss from angle-closure glaucoma precipitated by non-ophthalmological medication.
Haematopoietic stem cell transplantation (HSCT) is potentially curative for haematological diseases. New developments are improving its applicability and success.
A literature search was conducted on peripheral blood haematopoietic stem cell (PBHSC) mobilization, umbilical cord blood (UCB) transplantation, reduced intensity conditioning (RIC) and acute graft-versus-host disease (aGVHD).
PBHSC mobilization by granulocyte colony-stimulating factor and chemomobilization may fail in up to 30% of patients previously treated with extensive chemotherapy. New mobilization agents, notably the CXCR4 antagonist, have improved mobilization efficacy. UCB-HSCT is equally feasible in children and adults. RIC enables HSCT to be performed in patients who are elderly or with serious medical co-morbidities. RIC-HSCT is associated with increased frequency of graft failure and disease relapse. The prophylaxis and treatment of aGVHD are still problematic.
Novel strategies in PBHSC mobilization, utilization of UCB-HSCT and RIC-HSCT and prophylaxis and treatment of aGVHD, have not been critically appraised or compared with conventional strategies.
The safety and efficacy of novel mobilization agents have to be tested in normal allogeneic donors. Methods of increasing the cell dose or efficacy of UCB should be developed, to extend its use to adults. RIC-HSCT should be compared with conventional HSCT in young patients. Continuous efforts in defining the best prophylaxis and treatment of aGVHD should be made.
Bile acid malabsorption (BAM) is a syndrome of chronic watery diarrhoea with excess faecal bile acids. Disruption of the enterohepatic circulation of bile acids following surgical resection is a common cause of BAM. The condition is easily diagnosed by the selenium homocholic acid taurine (SeHCAT) test and responds to bile acid sequestrants. Idiopathic BAM (IBAM, primary bile acid diarrhoea) is the condition where no definitive cause for low SeHCAT retention can be identified.
Review of PubMed and major journals.
Evidence is accumulating that BAM is more prevalent than first thought. Management of chronic diarrhoea involves excluding secondary causes. Treatment of the condition is with bile acid binders.
SeHCAT testing is not widely performed, limiting awareness of how common this condition can be. The underlying mechanism for IBAM has been unclear.
Increasing awareness of the condition is important. Alternative mechanisms of IBAM have been suggested which involve an increased bile acid pool size and reduced negative feedback regulation of bile acid synthesis by FGF19. New sequestrants are available.
Further research into the precise mechanism of IBAM is needed. Improvements in the recognition of the condition and optimization of treatment are required.
Osteoporosis is among the chronic problems emerging as the human immunodeficiency virus (HIV)-positive population ages.
We reviewed the English language bibliography using Pubmed 2.0, Web of Science and Embase for relevant abstracts and articles.
The prevalence of low bone mineral density (BMD) and fracture is increased in the HIV-positive population.
The pathogenesis is multifactorial; there is some evidence that HIV infection is an independent risk factor and that highly active antiretroviral therapy has adverse skeletal effects.
Physicians should routinely review the bone health of all HIV patients.
More studies of the mechanisms of bone loss, the skeletal effects of antiretroviral therapy and the therapeutic outcome of bone-protective therapy in HIV-positive individuals are needed.
Mathematical models allow us to extrapolate from current information about the state and progress of an outbreak, to predict the future and, most importantly, to quantify the uncertainty in these predictions. Here, we illustrate these principles in relation to the current H1N1 epidemic.
Many sources of data are used in mathematical modelling, with some forms of model requiring vastly more data than others. However, a good estimation of the number of cases is vitally important.
Mathematical models, and the statistical tools that underpin them, are now a fundamental element in planning control and mitigation measures against any future epidemic of an infectious disease. Well-parameterized mathematical models allow us to test a variety of possible control strategies in computer simulations before applying them in reality.
The interaction between modellers and public-health practitioners and the level of detail needed for models to be of use.
The need for stronger statistical links between models and data.
Greater appreciation by the medical community of the uses and limitations of models and a greater appreciation by modellers of the constraints on public-health resources.
Anti-tumour necrosis factor (TNF) therapy is increasingly used in the management of inflammatory bowel disease; however, concerns have been raised regarding risk of infection with such drugs. Little is known about their effect upon viral infection.
A search of PubMed using the terms ‘infliximab’, ‘etanercept’, ‘adalimumab’ or ‘anti-TNF therapy’ combined with the names of specific viruses was performed. A search of cited papers was used to identify further relevant reports.
Numerous reports of the use of anti-TNF in patients with chronic or latent viral infection appear in the literature. Specific problems related to hepatitis B virus and varicella zoster virus may exist. The safety profile of anti-TNF in chronic viral infection is generally reassuring.
Numerous consensus statements relating to pre-treatment serology or vaccination have recently appeared; however, significant variation exists in their recommendations.
Increasing awareness of the implications of anti-TNF therapy on viral infection may allow safer use of such drugs.
The clinical and cost-effectiveness of screening for viral infections prior to anti-TNF requires further study.
Sports injuries in young athletes are a public health issue which deserves special attention. Effective prevention can be achieved with training programmes originating from the field of physical therapy and medicine.
A systematic literature search on injury prevention in youth sport was performed in the MEDLINE database.
For prevention programmes to reduce sports injuries, critical factors must be considered, such as training content, duration and frequency, as well as athlete compliance.
Home-based programmes could be inferior to supervised training, but are efficient if compliance is high. So far prevention programmes have focused on team sports and their efficiency in individual sports remains to be proven.
Active prevention programmes focusing specifically on the upper extremity are scarce. Initiatives enhancing the awareness of trainers, athletes and therapists about risk factors and systematic prevention measures should be encouraged.
Age-associated cognitive decline—or normal (non-pathological, normative, usual) cognitive ageing—is an important human experience which differs in extent between individuals. The determinants of the differences in age-related cognitive decline are not fully understood. Progress in the field is taking place across many areas of biomedical and psychosocial sciences.
The phenotype of normal cognitive ageing is well described. Some mental capabilities are well maintained into old age. From early adulthood, there are declines in mental domains such as processing speed, reasoning, memory and executive functions, some of which is underpinned by a decline in a general cognitive factor. There are contributions to understanding individual differences in normal cognitive ageing from genetics, general health and medical disorders such as atherosclerotic disease, biological processes such as inflammation, neurobiological changes, diet and lifestyle. Many of these effect sizes are small; some are poorly replicated; and in some cases, there is the possibility of reverse causation, with prior cognitive ability causing the supposed ‘cause’ of cognitive ability in old age.
Genome-wide scans are a likely source to establish genetic contributions. The role of vascular factors in cognitive ageing is increasingly studied and understood. The same applies to diet, biomarkers such as inflammation and lifestyle factors such as exercise. There are marked advances in brain imaging, affording better in vivo studies of brain correlates of cognitive changes. There is growing appreciation that factors affecting general bodily ageing also influence cognitive functions in old age.
Assessing the causes of death across all regions of the world requires a framework for integrating, and analysing, the fragmentary information that is available on numbers of deaths and their cause distributions. This paper provides an overview of the met and methods used by the World Health Organization to develop global-, regional- and country-level estimates of mortality for a comprehensive set of causes, and provides an overview of global and regional levels and patterns of causes of death for the year 2004. The paper also examines some of the data gaps, uncertainties and limitations in the resulting mortality estimates.
Deaths for 136 disease and injury causes were estimated from available death registration data (111 countries), sample death registration data (India and China), and for the remaining countries from census and survey information, and cause-of-death models. Population-based epidemiological studies and notifications systems also contributed to estimating mortality for 21 of these causes (representing 28% of deaths globally, 58% in Africa).
Ischaemic heart disease and cerebrovascular disease are the leading causes of death, followed by lower respiratory infections, chronic obstructive pulmonary disease and diarrhoeal diseases. AIDS and TB are the sixth and seventh most common causes of death, respectively, lower than in previous estimates. One-half of all child deaths are from four preventable and treatable communicable diseases. Globally, around 6 in 10 deaths are from non-communicable diseases, 3 from communicable diseases and 1 from injuries. Injury mortality is highest in South-East Asia, Latin America and the Eastern Mediterranean region. These results illustrate continuing huge disparities in risks and causes of death across the world.
Global mortality analyses of the type reported here have been criticized for making estimates of mortality for regions with limited, incomplete and uncertain data. Estimates presented here use a range of techniques depending on the type and quality of evidence. Better evidence on levels of adult mortality is needed for African countries.
Considerable gaps and deficiencies remain in the information available on causes of death. Nine of 10 deaths in 2004 occurred in low- and middle-income countries, reinforcing the fundamental importance of improving mortality statistics as a measure of health status in the developing world. Acknowledging the controversies around use of incomplete and uncertain data, systematic assessments and synthesis of the available evidence will continue to provide important inputs for global health planning.
Innovative methods involving sample registration, and the use of verbal autopsy questionnaires in surveys, are needed to address these gaps. Research on strategies to improve comparability of cause-of-death certification and coding practices across countries is also a high priority.
The optimal management of calcaneal fractures is controversial, as correlation between anatomical restoration and outcome has not been proven, and complications after surgery are frequent.
MEDLINE, EMBASE, CINAHL, Google scholar, the Cochrane Controlled Trials Register, and the Cochrane Musculoskeletal Injuries Group Trials Register were searched using the keywords ‘calcaneal’ and ‘fractures’, without time limits or restriction to language. Randomized and quasi-randomized trials were included. Two separate comparisons were identified in the trials: operative versus non-operative management (five studies), and impulse compression versus no impulse compression (one study). Two reviewers independently assessed trial quality, with a 12-item scale used by the Cochrane Collaboration.
Results showed no difference in residual pain, but favoured surgical management on ability to return to the same work and to wear the same shoes as before the fracture. Surgery reduced the need for subsequent subtalar fusion. workers’ compensation affected outcome.
It is unclear whether general health outcome measures, injury specific scores and radiographic parameters improve after operative management, and whether the benefits of surgery outweigh the risks.
The existing trials are of relatively poor quality.
There is still a need for a carefully designed large-scale trial comparing surgery and non-operative management. Other forms of fixation (external fixation or minimally invasive internal fixation) should be compared with ‘conventional’ surgery. Trials investigating joint reconstruction versus primary subtalar fusion for highly comminuted fractures, and impulse compression versus placebo could be of value.
Many tests are available for the investigation of patients with heart failure. The identification of the underlying aetiology of ventricular dysfunction is crucial as early treatment may limit or even reverse myocardial abnormalities.
This article describes cardiac radionuclide imaging techniques and their applications in ischaemic ventricular dysfunction. Evidence for the role of these techniques is summarized with particular reference to current guidelines.
Both positron emission tomography (PET) and single photon emission computed tomography (SPECT) techniques are widely validated for the detection of myocardial viability and their use is recommended in both national and international guidelines.
Although assessments of ventricular phase and myocardial innervation hold promise for the stratification of patients to cardiac resynchronization therapy, the poor performance of echocardiographic predictors of response in the recently published PROSPECT trial suggest that these techniques face a tough challenge.
The use of integrated multimodality imaging techniques such as PET/computed tomography to assess for ischaemic causes of left ventricular dysfunction is an area that is currently under investigation, as is the role of nuclear techniques in the assessment of stem cell retention, distribution and function when used in patients with heart failure.
Ongoing developments in radionuclide molecular imaging for assessment of angiogenesis, apoptosis and interstitial alterations during cardiac remodeling may have important implications for the prognosis and treatment of patients with heart failure.
The limit of each individual to perform a given type of exercise depends on the nature of the task, and is influenced by a variety of factors, including psychology, environment and genetic make up. Genetics provide useful insights, as sport performances can be ultimately defined as a polygenic trait.
We searched PubMed using the terms ‘sports’ and ‘genetics’ over the period 1990 to present.
The physical performance phenotypes for which a genetic basis can be suspected include endurance capacity, muscle performance, physiological attitude to train and ability of tendons and ligaments to withstand injury. Genetic testing in sport would permit to identify individuals with optimal physiology and morphology, and also those with a greater capacity to respond/adapt to training and a lesser chance of suffering from injuries.
Ethical and practical caveats should be clearly emphasized. The translation of an advantageous genotype into a champion's phenotype is still influenced by environmental, psychological and sociological factors.
The current scientific evidence on the relationship between genetics and sports look promising. There is a need for additional studies to determine whether genome-wide genotyping arrays would be really useful and cost-effective. Since exercise training regulates the expression of genes encoding various enzymes in muscle and other tissues, genetic research in sports will help clarify several aspects of human biology and physiology, such as RNA and protein level regulation under specific circumstances.