Showing papers in "British Medical Bulletin in 2010"

Health outcomes in economic evaluation: the QALY and utilities.

Abstract: The quality-adjusted life year (QALY) is routinely used as a summary measure of health outcome for economic evaluation, which incorporates the impact on both the quantity and quality of life. Key studies relating to the QALY and utility measurement are the sources of data. Areas of agreement include the need for a standard measure of health outcome to enable comparisons across different disease areas and populations, and the methods used for valuing health states in utility measurement. Areas of controversy include the limitation of the QALY approach in terms of the health benefits it can capture, its blindness towards equity concerns, the underlying theoretical assumptions and the most appropriate generic preference-based measure of utility. There is growing debate relating to whether a QALY is the same regardless of who accrues it, and also the issue as to who should value health states. Research is required to further enhance the QALY approach to deal with challenges relating to equityweighted utility maximization and testing the validity of underlying assumptions. Issues around choosing between condition-specific measures and generic instruments also merit further investigation.

Neglected tropical diseases

Abstract: Introduction: The neglected tropical diseases (NTDs) are infectious diseases that principally impact the world’s poorest people. They have been neglected for decades, initially as part of a general disregard for the developing world, and more recently due to the intensity of focus on HIV/AIDS, tuberculosis and malaria. Sources of data: Primary research and review articles were selected for inclusion using searches of PubMed and our existing collections. Results: There have been recent notable successes in NTD control. Dracunculiasis is approaching eradication. Leprosy and onchocerciasis are in decline. There are ambitious plans to eliminate trachoma and lymphatic filariasis. Investment in NTD control has high rates of economic return. Conclusion: Although there are proven strategies to control several NTDs, these diseases continue to cause a massive burden of morbidity. There is urgent need for more basic and operational research, drug and vaccine development, and greater prioritization by governments and international agencies.

Sarcopenia: characteristics, mechanisms and functional significance

Abstract: Sarcopenia reflects a progressive withdrawal of anabolism and an increased catabolism, along with a reduced muscle regeneration capacity. Muscle force and power decline more than muscle dimensions: older muscle is intrinsically weak. Sarcopenic obesity (SO) among the elderly corroborates to the loss of muscle mass increasing the risk of metabolic syndrome development. Recent studies on the musculoskeletal adaptations with ageing and key papers on the mechanisms of muscle wasting, its functional repercussions and on SO are included. Neuropathic, hormonal, immunological, nutritional and physical activity factors contribute to sarcopenia. Selective fast fibre atrophy, loss of motor units and an increase in hybrid fibres are typical findings of ageing. Satellite cell number decreases reducing muscle regeneration capacity. SO promotes further muscle wasting and increases risk of metabolic syndrome development. The proportion of fast to slow fibres seems maintained in old age. In elderly humans, nuclear domain is maintained constant. Basal protein synthesis and breakdown show little changes in old age. Instead, blunting of the anabolic response to feeding and exercise and of the antiproteolytic effect of insulin is observed. Further understanding of the mechanisms of sarcopenia requires disentangling of the effects of ageing alone from those of disuse and disease. The causes of the greater anabolic resistance to feeding and exercise of elderly women need elucidating. The enhancement of muscle regeneration via satellite cell activation via the MAPK/notch molecular pathways seems particularly promising.

Tendon augmentation grafts: a systematic review.

Abstract: Introduction: Several biomaterials are available to bridge large tendon defects or reinforce tenuous tendon repairs. Methods: We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL, and Embase databases using various combinations of the commercial names of each scaffold and the keywords ‘tendon’, ‘rotator cuff’, ‘supraspinatus tendon’, ‘Achilles tendon’, ‘scaffold’, ‘biomaterials’, ‘extracellular matrix’, ‘substitute’, and ‘devices’ over the years 1966–2009. All articles relevant to the subject were retrieved, and their bibliographies hand searched for further references in the context to biomaterials for tendon repair. Results: Many biomaterials are available for tendon augmentation. Scanty evidence is available for the use of these scaffolds. Discussion: The emerging field of tissue engineering holds the promise to use biomaterials for tendon augmentation. Preliminary studies support the idea that these biomaterials have the ability to provide an alternative for tendon augmentation. However, available data are lacking to allow definitive conclusion on the use of biomaterials for tendon augmentation. Additionally, the prevalence of postoperative complications encountered with their use varies within the different studies. Conclusion: Rather than providing strong evidence for or against the use of these materials for tendon augmentation, this study instead generates potential areas for additional prospective investigation.

Autologous growth factor injections in chronic tendinopathy: a systematic review

Abstract: Chronic degenerative tendinopathies are frequent and difficult to treat. Tendon healing and regeneration may be improved by injecting autologous growth factors obtained from the patient's blood. Autologous growth factors can be injected with autologous whole blood or platelet-rich plasma (PRP). Electronic databases were searched for prospective clinical trials on treatment with autologous growth factors of patients with chronic tendinopathy. Chronic tendinopathy in this study included wrist extensors, flexors, plantar fasciopathy and patellar tendinopathy. Studies examining the treatment of other tendinopathies were not identified. The Physiotherapy Evidence Database score was used to examine the methodological quality of the assessment, and a qualitative analysis was performed with the levels of evidence. There are many proposed treatment options for chronic tendinopathy. Treatments in the form of injections with autologous whole blood or PRP are increasingly used in clinical practice. There are high expectations of these regenerative injections, and there is a clear need for effective conservative therapies. All studies showed that injections of autologous growth factors (whole blood and PRP) in patients with chronic tendinopathy had a significant impact on improving pain and/or function over time. However, only three studies using autologous whole blood had a high methodological quality assessment, and none of them showed any benefit of an autologous growth factor injection when compared with a control group. At present, there is strong evidence that the use of injections with autologous whole blood should not be recommended. There were no high-quality studies found on PRP treatment. There is limited evidence to support the use of injections with PRP in the management of chronic tendinopathy. There is growing interest in the working mechanisms of autologous growth factors. The amount and mixture of growth factors produced using different cell separating systems are largely unknown and it is also uncertain whether platelet activation prior to injection is necessary. These variables should be taken into account when starting clinical studies. A good experimental model for studying tendinopathy would be helpful for basic research. Future clinical studies using a proper control group, randomization, blinding and validated disease-specific outcome measures for pain and function are needed.

Socio-economic inequalities in childhood mortality in low- and middle-income countries: a review of the international evidence

Abstract: Introduction: In low- and middle-income countries (LMICs), the probability of dying in childhood is strongly related to the socio-economic position of the parents or household in which the child is born. This article reviews the evidence on the magnitude of socio-economic inequalities in childhood mortality within LMICs, discusses possible causes and highlights entry points for intervention. Sources of data: Evidence on socio-economic inequalities in childhood mortality in LMICs is mostly based on data from household surveys and demographic surveillance sites. Areas of agreement: Childhood mortality is systematically and considerably higher among lower socio-economic groups within countries. Also most proximate mortality determinants, including malnutrition, exposure to infections, maternal characteristics and health care use show worse levels among more deprived groups. The magnitude of inequality varies between countries and over time, suggesting its amenability to intervention. Reducing inequalities in childhood mortality would substantially contribute to improving population health and reaching the Millennium Development Goals (MDGs). Areas of controversy: The contribution of specific determinants, including national policies, to childhood mortality inequalities remains uncertain. What works to reduce these inequalities, in particular whether policies should be universal or targeted to the poor, is much debated. Areas timely for developing research: The increasing political attention for addressing health inequalities needs to be accompanied by more evidence on the contribution of specific determinants, and on ways to ensure that interventions reach lower socio-economic groups.

Genetics and sports.

Abstract: Introduction: 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. Sources of data: We searched PubMed using the terms ‘sports’ and ‘genetics’ over the period 1990 to present. Areas of agreement: 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. Areas of controversy: 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. Emerging areas for developing research: 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.

Measuring activity levels of young people: the validity of pedometers

Abstract: The valid measurement of physical activity has the potential to be a very useful tool in countering the obesity epidemic. Previously, reviews have been carried out to investigate the validity of pedometers among adults. This paper aimed to carry out a similar review among children. A literature search was performed in PubMed, Web of Science, PsycINFO, CINAHL and SportDISCUS. Here, 25 papers investigating the validity, reliability and feasibility of pedometers for children were included in the study. Pedometers correlated highly in terms of both criterion (direct observation) and convergent validity (heart-rate monitor, accelerometer). Intra- and inter-unit reliability was also consistently high. Few studies report on feasibility issues of pedometer use in children, particularly compliance, reactivity and dealing with missing data. Given that they are both cheap and easy to use, pedometers can be effectively utilized as a valid determinant of physical activity levels among children and adolescents, particularly in large-scale epidemiological studies. There remains a need for accepted outliers and proper protocol regarding missing data.

A 100 year update on diagnosis of tuberculosis infection

Abstract: Background: 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. Areas of agreement: 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. Areas of controversy: 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? Growing points: 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 BCGvaccinated persons with false-positive TST results.

New technologies for the detection of circulating tumour cells.

Abstract: The vast majority of cancer-related death is due to the metastatic spread of the primary tumour. Circulating tumour cells (CTC) are essential for establishing metastasis and their detection has long been considered as a possible tool to assess the aggressiveness of a given tumour and its potential of subsequent growth at distant organs. Conventional markers are not reliable in detecting occult metastasis and, for example, fail to identify approximately 40% of cancer patients in need of more aggressive or better adjusted therapies. Recent studies in metastatic breast cancer have shown that CTC detection can be used as a marker for overall survival and assessment of the therapeutic response. The benefits of CTC detection in early breast cancer and other solid tumours need further validation. Moreover, optimal CTC detection techniques are the subject of controversy as several lack reproducibility, sensitivity and/or specificity. Recent technical advances allow CTC detection and characterization at the single-cell level in the blood or in the bone marrow. Their reproducibility propels the use of CTC in cancer staging and real-time monitoring of systemic anticancer therapies in several large clinical trials. CTC assays are being integrated in large clinical trials to establish their potential in the management of cancer patients and improve our understanding of metastasis biology. This review will focus on the techniques currently used, the technical advancements made, the limitations of CTC detection and future perspectives in this field.

Rating scales for low back pain

Abstract: Introduction: During the past decades several rating scales have been developed to assess the functional status of patients with low back pain. Methods: We performed a search using the keywords ‘spine’ in combination with ‘scoring system’, ‘scale’, ‘scores’, ‘outcome assessment’, ‘low back pain’ and ‘clinical evaluation’. Results: Twenty-eight scoring systems are currently available for the evaluation of low back pain. Each of them evaluates low back pain using specific variables. All these scoring systems are presented. Discussion: Although many scoring systems have been used to evaluate the back function, we are still far from a single outcome evaluation system that is reliable, valid and sensitive to clinically relevant changes, taken into account both patients’ and physicians’ perspective and is short and practical to use. Conclusion: Further studies are required to evaluate the reliability, validity and sensitivity of the low back pain scoring systems used in the common clinical practice.

Palliative care for people with dementia.

Abstract: The number of people with dementia will rise dramatically over the next 20 years. Currently, one in three people over the age of 65 will die with dementia. A PubMed search using MeSH headings for ‘dementia’ AND ‘palliative care’ and for specific areas, i.e. enteral feeding. National reports, UK guidelines and policies were also consulted. Advanced dementia is now being perceived as a ‘terminal illness’ with a similar symptom burden and prognosis to advanced cancer. People with dementia have poor access to good quality end-of-life care. Interventions such as antibiotics, fever management policies and enteral tube feeding remain in use despite little evidence that they improve quality of life or other outcomes. Research is required on the effectiveness of ‘holistic’ palliative care, outcome measures and the impact on carers and families.

Policy strategies to reduce waits for elective care: a synthesis of international evidence

Abstract: This synthesis seeks to assess and explain the effectiveness of policy interventions to reduce elective wait times or lists. PubMed, EMBASE, EconLit, and grey literature were systematically searched for relevant studies and reviews. Strategies with the strongest evidence base include paying for activity, buying capacity locally and setting targets with strong incentives. There is also evidence for improving the use of existing capacity. Limiting demand through rationing can reduce waits, but is ethically problematic. Short-term injections of funding, cross-border treatment schemes, unenforced targets and promotion of private health insurance had the weakest evidence. Available evidence favours options that act fairly directly on supply, demand or local organizations' behaviour, over indirect strategies that depend on a 'domino effect'. Further research is needed to determine how to achieve major, system-wide improvements in the use of capacity.

Nontuberculous mycobacteria: opportunistic environmental pathogens for predisposed hosts.

Abstract: Nontuberculous mycobacterial (NTM) infections are caused by environmental mycobacteria. Patients with pulmonary NTM disease usually have predisposing lung abnormalities. Diagnostic methods are evolving. Treatment is largely empiric. Data were extracted from peer reviewed publications, guidelines, and case series. Progressive NTM lung disease should be treated. Multidrug regimens are mostly macrolide based and are occasionally complemented by lung resection. Disease persistence and relapse are not uncommon and are a greater problem with so-called rapid-grower NTM infections. Some of the issues considered in this review are: the role of antibiotic susceptibility testing in predicting treatment effectiveness, optimal drug combinations, daily vs. intermittent dosing intervals for different NTM infections and disease severity, when the goal of cure should be replaced with observation or palliation, and patient selection for surgery. Future needs for development and research include improved epidemiology, definition of genetic and other risk factors, definition of predictors of treatment outcome, multicenter treatment studies, new drug discovery and animal models of disease and treatment.

Multiple sclerosis: a practical overview for clinicians

Abstract: Multiple sclerosis (MS) is the commonest disabling neurological condition to afflict young adults and therefore has a high social burden. Over several decades, there has been a considerable progress in the understanding of the disease pathogenesis as well as in the clinical management of MS patients. The emphasis in managing MS patients has shifted to multidisciplinary teams working in specialist groups. A review of the literature was conducted using MedLine to identify recent advances in MS. The current consensus is that MS is an autoimmune disease triggered by environmental agents acting in genetically susceptible people. Based on that concept, new methods of immune intervention procedures have been introduced into clinical practice. Licensed first-line disease-modifying therapies reduce the MS attack or relapse rate by a third and delaying short-term disease progression. More effective therapies have emerged; however, these are associated with increased risks. New clinical and pathological insights are making us question the aetiology and pathogenesis of MS. The recognition of pathological heterogeneity has raised the question of whether MS is a single disease entity or a syndrome. Recent evidence suggests that the pathological subtype may predict therapeutic response to specific therapies. A new novel auto-antibody has defined a subset of neuromyelitis optica or Devic's disease as being distinct from MS. This is an attractive concept that is not widely accepted. The observation that MS progresses despite immunosuppressive therapy suggests that MS may be a neurodegenerative disease with overlapping immune activation possibly in response to the release of central nervous system auto-antigens. The development of neuroprotective therapies for MS is required to prevent the devastating effects of long-term disability as a result of progressive disease.

The policy agenda for prevention and control of non-communicable diseases

Abstract: Robust national policies and strategies developed and owned by national authorities are fundamental for prevention and control of non-communicable diseases (NCDs). The objective of this paper is to address broad policy areas in respect of NCD prevention and control from a public health perspective, with a special focus on low- and middle-income countries (LMIC). The paper is a condensation of current World Health Organization (WHO) reports in this field supported by relevant literature obtained from a Medline search for the period 2000-2010. There is a strong evidence base that underpins the NCD policy agenda. National NCD policies can make a substantive impact on public health in LMIC if they are geared to addressing primary prevention and equity of health systems. National NCD policies help to catalyse, and coherently integrate regulatory, legislative and multisectoral actions across health and other health relevant sectors. Such multisectoral action is integral for creation of conducive environments to support healthy behaviours. There is agreement that health systems need reconfiguration to ensure equitable access to essential NCD interventions. Although the magnitude of the NCD burden is high and is growing in LMIC, international development assistance to address the burden remains negligible. How exactly gaps in formulation, and implementation of NCD policies can be addressed when there are severe limitations in human resource capacity, financial resources and competing health priorities in LMIC is not clear. Context-specific research is required to address implementation gaps in NCD policy, as policy development and implementation are driven by political realities and cultural specificities. Research is also needed to develop innovative approaches for revenue generation for prevention and control of NCDs.

Policies for reducing delayed discharge from hospital

Abstract: Introduction: Delayed discharge from acute hospital has been a cause of concern for the last 10 years. Older people with complex health needs are particularly vulnerable to delayed discharge with negative consequences for their health and wellbeing. Source of data: Review of the literature on the impact of the Community Care (Delayed Discharge) Act (2003) and subsequent policy initiatives on delayed discharges. Areas of agreement: A number of cross-institutional complexities contribute to delayed discharges. Policy measures have contributed positively to reducing delayed discharges. Investment in intermediate care services has provided a range of services to promote maximum independence for older people after acute hospital admission. Joint working between health and social services is necessary to prevent delayed discharges. Areas of controversy: Pressure to achieve rapid hospital throughput may be contributing to older people leaving hospital too soon and to recent increases in hospital re-admission rates. Policy measures are extending to older people with mental health problems.

Living-donor liver transplantation in adults

Abstract: Introduction The technique of paediatric living-donor liver transplantation (LDLT) has become standardized. In adults, however, there is scope for innovation. Unlike cadaveric whole-size liver transplantation and paediatric LDLT, size matching between the liver graft and the recipient by body weight has been a major challenge in adult LDLT because it is important to provide an adequate graft mass to the recipient while leaving a sufficient mass of remnant liver in the donor to ensure donor safety. Growing points In adult LDLT, liver grafts have been selected to meet graft-recipient size-matching requirements. In 1996, the Hong Kong group pioneered the use of the right-lobe grafts vein to overcome the volume insufficiency often encountered with the left-lobe liver grafts. Subsequently, the Asan group introduced modified right-lobe grafting with interposition vein grafts to drain the venous outflow of the anterior sector, thus increasing the functioning hepatocyte mass, and this group initiated dual left-lobe liver grafts to overcome both donor risk and volume insufficiency. Areas of agreement and controversy Although the surgical procedures for both donors and recipients are more complex for adult LDLT than for whole-organ deceased donor transplantation, the outcomes in large-volume centers are now similar. Accordingly, the indications for adult LDLT are continually being expanded. Areas timely for developing research In performing these procedures, it is crucial to minimize the risks of morbidity and mortality to the healthy live donor. This review focuses on the current technical development and discusses the ethical issues of adult LDLT.

Coercion and compulsion in community mental health care

Abstract: There is ongoing debate in the UK as to the place of coercion and compulsion in community mental health care. Recent changes in service provision and amendments to the Mental Health Act in England and Wales have increased the scope for compulsion in the community. This has intensified the debate revealing fault lines in the psychiatric and legal professions. Despite powerful arguments from all sides there is little empirical evidence to inform this debate at a clinical or a theoretical level. This review utilizes evidence from articles in peer reviewed journals. Papers were identified from electronic databases, the authors' databases of relevant literature and personal correspondence with experts in the field. The evidence base is relatively small but is expanding. It has been demonstrated that informal coercion is common in USA mental health services and can be experienced negatively by patients. There is evidence that powers of compulsion in community mental health care are used frequently when available and their availability is generally seen as positive by clinicians when practice becomes embedded. The evidence for the effectiveness of compulsion in community mental health care is patchy and conflicting, with randomized or other trials failing to show significant benefits overall even if secondary analyses may suggest positive outcomes in some subgroups. There are widespread regional and international differences in the use of community compulsion. Research examining treatment pressures (or 'leverage') and the subjective patient experience of them appears to be expanding and is increasing our awareness and understanding of these complex issues. There is an urgent need for evidence regarding the usefulness and acceptability of compulsion in the community now that powers have been made available. Trials of the effectiveness of compulsion are needed as is qualitative work examining the experiences of those involved in the use of such orders. These are needed to help clinicians utilize the powers available to them in an informed and judicious fashion and to ensure adequate training.

Temporal sequence of greyscale ultrasound changes and their relationship with neovascularity and pain in the patellar tendon.

Abstract: Objective Ultrasound (US) imaging has revealed distinct types of greyscale abnormalities in the patellar and Achilles tendons, including diffusely thickened tendons and tendons containing a hypoechoic region. The relationship between these greyscale abnormalities and their clinical relevance is unknown. This study investigated the temporal sequence in greyscale abnormalities as well as the relationship between greyscale abnormalities, Doppler flow and pain. Methods Patellar tendon pain (single leg decline squat test) and ultrasound imaging (greyscale (normal, diffuse thickening, hypoechoic), presence of Doppler flow) were assessed bilaterally among 58 volleyball players at monthly intervals during a 5-month season. The probability of transition between the greyscale ultrasound groups was calculated for each month and totalled over the season (prospective) and the relationship between these groups and the presence and intensity of pain and the presence of Doppler flow were investigated (cross-sectional investigation). Results Tendons with normal US were more likely to transition to diffuse thickening than to a hypoechoic region. Tendons containing a hypoechoic region were more likely to transition to diffuse thickening rather than to a normal US appearance. Hypoechoic regions were more likely to be painful (59%) and contain Doppler flow (42%) than tendons with diffuse thickening (pain in 43% and Doppler flow in 6%). Conclusions The transitions identified between normal, diffusely thickened tendons and those containing a hypoechoic region suggests that these greyscale US changes may represent different phases of tendon pathology. Tendons containing a hypoechoic region are more likely to be painful and contain Doppler flow than diffusely thickened tendons.

Motor neuron disease: systematic reviews of treatment for ALS and SMA

Abstract: Introduction: There is no curative treatment for the common motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Nevertheless, there is an increasing volume of published studies. This review assesses the current evidence for treatment of these conditions. Sources of data: Primarily, the systematic reviews of the Cochrane Collaboration, with additional reference to other systematic reviews and online sites. Areas of agreement: Riluzole remains the only medication with demonstrated efficacy and regulatory approval for the treatment of ALS. Areas of controversy, growing points and areas timely for developing research: The design of clinical trials and the publication of unsatisfactory studies, in both human and animal models, continue to cause confusion in advising on patient management. Improvements in trial design, critical assessment of studies for publication and avoidance of bias towards publication of positive results are needed. A better understanding of pathogenesis should lead to more potent interventions.

Community-associated methicillin-resistant Staphylococcus aureus infections.

Abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been recognized for over a decade, and usually refers to MRSA identified in previously healthy individuals with no recognized MRSA risk factors. Infections range from minor skin and soft tissue infections, through to severe pneumonia and necrotizing fasciitis. This review summarizes the current data on the epidemiology and molecular features of CA-MRSA, in addition to diagnosis and therapeutic measures. We also refer to current national guidelines for the management of these infections. Areas of agreement include the important genotypic and phenotypic differences of community MRSA strains compared with hospital strains. Areas of controversy include the precise epidemiological definition of community-acquired/associated MRSA. Fortunately, true CA-MRSA can be differentiated from hospital MRSA by molecular techniques, as discussed herein. Recent interest has focused on the changing epidemiology of CA-MRSA. Worldwide, CA-MRSA is now seen outside of the initial specific population groups, and in the USA, the successful USA300 community strain is beginning to spread back into hospitals. Reasons why USA300 remains relatively uncommon in Europe are unclear. Topics timely for research include the investigation of the epidemiology of infections and evolutionary genomics.

Nausea and vomiting in advanced cancer

Abstract: Nausea and vomiting are distinct symptoms, commonly occurring together but which should be assessed separately. Both are prevalent in patients with advanced cancer. Data are taken from The Cochrane Library (2010) and Ovid MEDLINE (1966-2010). Most current guidelines advocate an aetiology-based approach to the management of nausea and vomiting. Choice of anti-emetic is based on a clinical assessment of the likely pathophysiological component of the emetogenic pathway that is being triggered and selecting an anti-emetic drug that blocks the key receptors involved. Some authors propose a more empirical approach. The limited available evidence would suggest that both an empirical or aetiology-based approach may have similar overall efficacy. There are no published studies directly comparing the two. Standardized assessment and outcome tools are needed to enable well-designed studies to establish efficacy for conventional agents and also compare efficacy with the newer, more expensive ones.

Viral haemorrhagic fevers imported into non-endemic countries: risk assessment and management

Abstract: Background: Viral haemorrhagic fevers (VHFs) are severe infections capable of causing haemorrhagic disease and fatal multi-organ failure. Crimean-Congo, Marburg, Ebola and Lassa viruses cause both sporadic cases and large epidemics over wide endemic areas. Sources of data: Original articles and reviews identified by PubMed search and personal reading; European and United States national guidance and legislation. World Health Organization information, documents and reports. VHFs cause significant morbidity and mortality in their endemic areas; they can cause healthcare-related infections, and their broad diversity and range are increasingly recognized.

Management of combined ACL-MCL tears: a systematic review.

Abstract: Introduction: The optimal management for combined anterior cruciate ligament–medial collateral ligament (ACL–MCL) injuries is controversial. Sources of data: We performed a literature search using Medline, Cochrane and Google Scholar using the keywords: ‘ACL’ and ‘MCL’ in combination with ‘surgery treatment’, ‘conservative treatment’, ‘surgery management’, ‘conservative management’, ‘surgical treatment’ and ‘surgical management’. We identified 23 published studies. Areas of agreement: Conservative and surgical management for combined ACL– MCL injuries resulted in different functional outcomes. The Coleman Methodology Score showed great heterogeneity in terms of study design, patient characteristics, management methods and outcome assessment and generally low methodological quality. Areas of controversy: Given the heterogeneity in terms of treatment and results, we did not find a univocal trend over the years regarding MCL management (conservative or surgical). The use of several scoring systems did not allow us to compare outcomes in the different studies. Growing points: There is a need for a common validated scale for clinical measurements for ACL–MCL injuries, so as to allow easier and more reliable comparison of outcomes in different studies. To improve diagnostic certainty of combined ACL–MCL injuries, all patients should have imaging assessment (MR and stress-radiography) in addition to clinical examination. Areas timely for developing research: There is a need to perform appropriately powered randomized clinical trials of conservative and surgical treatment of combined ACL–MCL injuries, using standard diagnostic assessment, common and validated scoring system comparing reported outcomes and duration of followup more than 2 years.

Prevention and treatment of microvascular disease in childhood type 1 diabetes

Abstract: Introduction: The incidence of type 1 diabetes (T1D) is increasing worldwide, particularly in children, and is associated with a significant burden, mainly related to the development of vascular complications. The prevention and treatment of microvascular complications, which include nephropathy, retinopathy and neuropathy, are of paramount importance to decrease the associated mortality and morbidity. Sources of data: A literature search was performed on Medline and articles on microvascular complications, with particular emphasis on the increasing incidence of childhood T1D and its implications on prevention and treatment of complications, were selected. Areas of agreement: The incidence of childhood T1D is increasing. Early identification of subjects at risk for long-term complications and early implementation of preventive and therapeutic strategies are fundamental in order to reduce the burden associated with microvascular complications of diabetes. Improving glycaemic control is the principle way of preventing and treating T1D complications. Areas of controversy: In adults with T1D and microvascular complications, treatment with anti-hypertensive drugs and statins is increasingly common, whereas there are no definitive indications for treatment with these drugs in children and adolescents with early signs of complications. Growing points: There is growing interest in the development of new preventive and therapeutic strategies targeting specific pathways implicated in the pathogenesis of microvascular complications. Areas timely for developing research: Investigations to clarify genetic and environmental factors implicated in the pathogenesis of microvascular complications could lead to the identification of biochemical markers with high predictive values, to be used as a guide for screening and intervention programmes.

Neuropharmacology of addiction and how it informs treatment

Abstract: Our knowledge about the neuropharmacology of addiction is increasing and is leading to more informed development of pharmacotherapy. Although the dopaminergic mesolimbic system plays a central role in ‘liking’, reward and motivation, medications directly targeting it have not proved a very fruitful approach to treating addictions. A review of the literature was performed to find articles relating current and developing pharmacological treatments in the clinic and their underlying neuropharmacology. We focussed on the most common addictions for which pharmacology plays an important role. By characterizing what neurotransmitters modulate this dopaminergic pathway, new medications are now in the clinic and being successfully applied to treat a variety of addictions. In addition to modulating this reward pathway, alternative approaches in the future will target learning and memory, improving impulse control and decision-making.

The molecular and cellular biology of lung cancer: identifying novel therapeutic strategies

Abstract: Introduction: Lung cancer is the commonest fatal malignancy in the developed world. Survival rates for lung cancer have not changed significantly over the past 30 years. Sources of data: This report is a systematic review of the literature on our current understanding of lung cancer biology. Searches were carried out using PUBMED. 1990‐2010. Areas of agreement: A concerted effort to reduce cigarette smoking and nicotine addiction is required. A better understanding of the biology of lung cancer will lead to the identification of earlier diagnostic markers and improved therapy. Areas of controversy: How chronic inflammatory disorders such as COPD and lung fibrosis contribute to lung cancer development is incompletely understood. Growing Points: Developing novel biological agents to target lung cancer. New microarray-based technologies provide new methods for predicting prognosis and response to treatment.

New insights in cough.

Abstract: Chronic cough is common, blights patients' lives and is hard to treat. Chronic cough patients demonstrate high objective cough rates and as a group have increased cough reflex sensitivity. However, conventional cough challenge techniques show substantial overlap with normal subjects. This suggests that other important mechanisms have yet to be determined. For the last two decades, chronic cough has been considered to be caused by gastro-oesophageal reflux, post-nasal drip or asthma. However, many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. In addition, many chronic cough patients do not have an identifiable cause. This raises questions about the concept of a triad of treatable causes for chronic cough. Our current understanding of the neurophysiology of the cough reflex is largely derived from animal work with limited data in humans. By analogy with chronic pain syndromes, both peripheral and central sensitization may be important mechanisms in chronic cough, and are under active investigation. We need to understand the mechanisms underlying sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Only then will we develop effective interventions.

Pharmacological and environmental factors in primary angle-closure glaucoma

Abstract: Introduction or background: 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. Sources of data: This review of the ophthalmic literature provides a clinical summary of primary angle-closure glaucoma (PACG) and its management. Areas of agreement: External stimuli (pharmacological and environmental) may induce acute, and more often, asymptomatic angle closure, which carries a significant risk of glaucoma. Growing points: 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. Areas for developing research: 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.