Public health practice is characterized by measuring population health, assessing needs for health care and the provision (directly or indirectly) of services to protect and promote the public's health. It is increasingly explicitly concerned with issues of equity.
Publications discussing ethical issues in public health.
Unlike the duties of clinicians, professional standards for public health practice are not well defined. An ethics framework would help the development and implementation of public health policy.
Public health strategies have been criticized for being paternalistic and restrictive of personal choice behaviours or for being too pragmatic, and appearing to endorse illegal activities.
Historically public health programmes have been delivered at a population level for large groups of people with varying capacity to benefit. Within more autonomy, consumer-orientated political environment, strategy must be more targeted to facilitate healthy choices as defined by the individual.
Debate is needed on the aims of public health, rights and responsibilities of professionals and citizens and mechanisms for developing and implementing policy.
The subject of ‘global health’ can be considered from multiple points of view. While epidemiologists might describe global health problems in categories of pathology groups, social scientists might consider the problem from the stand point of institutional and infrastructural strengths and failings. An over-arching theme, however, is that the distribution of the burden of ill health is disproportionately carried by the poor. This paper aims to defend the idea that inequality should be considered the main priority in global ill health.
Review of the literature, personal communications and the WHO commission on the Social Determinants of Health.
The extent and urgency of global health problems.
The cause of ill health and the appropriate intervention.
We all need a deeper appreciation of the plight of the poor and the extent to which suffering can be mitigated by striving for a more equitable future.
Research into the broader global forces that impact on economic disparity (for the better and the worse) and the extent to which they effect measureable health outcomes is an extremely important area for research in this day and age.
Debate over relationships between economic growth, wealth, health and health inequity is long-standing and ongoing. The main message of this paper is that economic growth, while necessary, is not a sufficient condition in itself for achieving equitable health.
This review surveys and draws on research into principal factors commonly linked with improving health—income, health care, individual behavior—suggesting, using work from the Commission on Social Determinants of Health, that these are better understood in a broader social determinants of health framework.
The paper acknowledges that post-war globalization has seen significant growth, poverty reduction and greater economic resources at individual and household levels all of which can contribute to better health. But it also highlights renewing inequity in global health during the period.
It argues that over-reliance on market-driven growth, which fails to address deep-rooted social inequalities in economic resources key to accessing social determinants of health, and in the key determinants of health themselves have contributed to increasing inequity in health outcomes.
Commitment to market-driven growth remains evident in national policy-making worldwide.
With increasing health inequity, and calamitous global economic events in 2008–09, the centrality of this commitment needs urgently to be reviewed.
Dementia, Alzheimer's disease and vascular dementia being two main causes, is major and growing health problem. Vascular risk factors are thought to be involved in the causation of both dementias.
A review of the literature was conducted using MedLine to identify current evidence for role of vascular risk factors as potential targets in preventing dementia. Cross-references were hand searched.
The evidence from prospective epidemiological studies suggests that optimizing the control of vascular risk factors such as hypertension, high cholesterol, diabetes, smoking and heart disease may prevent dementia. However, this has been proven in randomized placebo-controlled trials (RCT) for only hypertension.
Dementia is a secondary outcome in most RCTs and it is not known if there is a therapeutic time window between mid- and late-life when interventions are most effective. Also, we do not know precise mechanisms by which interventions for vascular risk factors offer brain protection.
Our research suggests that asymptomatic cerebral emboli, which are preventable, may be involved in the causation of dementia.
There is a need for RCT targeting multiple vascular risk factors in patients at high risk of dementia such as those with mild cognitive impairment.
Schizophrenia is a debilitating psychiatric disorder that imposes a considerable burden on sufferers, their families and society. The prominent involvement of genes, combined with the complexity and relative inaccessibility of the brain has led many to suggest that the identification of specific risk loci offers the best chance of understanding pathogenesis.
Recent genome-wide association studies (GWAS) and copy number variation (CNV) publications have been included in this review along with key papers from the fields of schizophrenia, functional psychoses and complex disease mapping.
Recent GWAS have now shown that both common alleles of small effect and rare alleles of moderate to large effect contribute to the high heritability of schizophrenia.
It is well known that many schizophrenic patients suffer symptoms seen in patients with bipolar disease and vice versa. There is now considerable interest in using aetiologically relevant risk factors, including genes, to explore the validity of the contemporary system of classification.
Rare CNVs have been shown to play a role in at least some cases of schizophrenia and it is highly predictable that this figure will rise with the use of technologies with higher resolution or that are better designed to assay common CNVs reliably.
The findings with common alleles thus far point to overlap in the genetic risk for schizophrenia and bipolar disorder, while the specific CNVs implicated in schizophrenia also increase susceptibility to a range of developmental disorders, including autism, mental retardation, attention deficit-hyperactivity disorder (ADHD) and epilepsy.
Open tibial fractures have been studied extensively in adults, and detailed treatment strategies have been developed: wound irrigation and debridement, fracture stabilization and delayed primary wound closure or early flap coverage are basic principles of management. No clear guidelines regarding the management of open tibial fractures in children exist.
We searched Medline, Embase, Cochrane, CINAHL and Google Scholar databases using the keywords: ‘open’, ‘tibia’, ‘fracture’, ‘children’, ‘paediatric’, ‘pediatric’, ‘external fixation’, ‘nailing’. Fourteen clinical studies were included. Quality of the studies was assessed using the Coleman Methodology Score.
Age above 10 years and grade III (severe) open fractures are associated with complications and outcomes similar to those in adults.
It is unclear whether open fractures of the tibia in children should be managed according to the principles followed in adults. Many authors support primary skin closure and non-operative management for grade I open fractures. There is no clear effect of fracture fixation method on time to union.
The quality of the studies was relatively poor. Patients' age affects outcome; adolescents should probably be managed as adults.
Carefully designed prospective cohort studies including a large number of children would be of value. Adequate follow-up is necessary to assess the long-term effects in the growing skeleton. The efficacy of flexible intramedullary nailing for open fractures needs further evaluation. Outcome studies based on general health measures are needed.
Clostridium difficile is the commonest cause of nosocomial diarrhoea. The epidemiology and clinical phenotype of the disease has dramatically changed with the global emergence of a virulent strain of C. difficile.
This review was compiled using data from individual studies and review articles identified from PubMed. The retrieved articles were also examined for additional references.
Appropriate and timely infection control measures are required to control C. difficile infection (CDI) in the hospital environment, and either oral metronidazole or vancomycin remains the mainstay of treatment depending on the severity of infection.
The optimal method for diagnosing CDI remains unclear, as does the best therapeutic strategy for the management of multiple relapses.
Studies of new antimicrobial agents with activity against C. difficile are required to improve the management of multiply relapsing disease. The use of novel therapeutic approaches that do not require antimicrobials requires urgent research, including the use of immunological or vaccine-based regimen, bacteriotherapy or C. difficile-specific bacteriophages.
Active sports participation can be important in some patients with degenerative joint disease in the lower limb. We investigated whether this is possible after an osteotomy for osteoarthritis of the hip, knee and ankle joints.
We performed a literature search using Medline, Cochrane, CINAHL and Google Scholar with no restriction to time period or language using the keywords: ‘osteotomy and sports’. Eleven studies (all level IV evidence) satisfied our inclusion and exclusion criteria. Nine reported on high tibial osteotomies, one on periacetabular osteotomies and one on distal tibial osteotomies. The Coleman Methodology Score to assess the quality of studies showed much heterogeneity in terms of study design, patient characteristics, management methods and outcome assessment.
Participation in recreational sports is possible in most patients who were active in sports before lower limb osteotomy. In no study were patients able to participate in competitive sports.
Intensive participation in sports after osteotomy may adversely affect outcome and lead to failures requiring re-operation.
Patients may be able to remain active in selected sports activities after a lower limb osteotomy for osteoarthritis. More rapid progression of arthritis is however a possibility.
Prospective comparative studies investigating activities and sports participation in age-matched patients undergoing osteotomy or joint replacement could lead to useful conclusions. Increased activity and active sports participation may lead to progression of arthritis and earlier failure requiring additional surgery.
Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH).
We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH.
VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo–pituitary–adrenal axis and psychological factors have all been implicated in the generation of VPH.
Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety.
The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development.
Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.
This review identifies an agenda for global health by highlighting the current ‘grand challenges’ related to governance.
Literature from the disciplines of health policy and medicine, conference presentations and documents, and materials from international agencies (such as the World Health Organization).
The present approach to global health governance has proven to be inadequate and major changes are necessary.
The source of problems behind the current global health governance challenges have not always been agreed upon, but this paper attempts to highlight the recurrent themes and topics of consensus that have emerged in recent years.
A solution to the ‘grand challenges’ in global health governance is urgently needed and serves as an area for developing research.
Cellular reprogramming is the process of directing mature cells to a primitive state of gene expression.
Medline searches using the keywords ‘pluripotency’, ‘induce’ (and derivatives), and/or ‘stem’ limited to the years 2006 to the present and other selected literature known to the author.
Since 2006, there has been a cavalcade of scientific works describing so-called ‘direct reprogramming’ wherein somatic cells are forced into a state of gene expression very similar to embryonic stem cells. These findings build upon prior research using nuclear transfer (cloning) and even older efforts to understand developmental processes.
While already of tremendous research value, it remains to be seen how (if) direct reprogramming methodologies will be refined for clinical use.
A greater understanding of epigenetics, the process by which different patterns of gene expression are established, maintained and redirected, will continue to be enlightened by advances in cellular reprogramming.
Rotaviruses (RVs) are an important cause of acute gastroenteritis in infants and young children worldwide, resulting in more than 600 000 deaths per annum, mainly in developing countries. Since the 1980s, there has been intensive research on the development of RV vaccine candidates, and since 2006 two vaccines have been licensed in many countries.
The scientific literature since the 1970s has been consulted, and the results of original research carried out in authors' laboratories were used.
There are firmly established data on virus particle structure, genome composition, gene–protein assignment, protein-function assignment (incomplete), virus classification, the mechanisms of several steps of the replication cycle (adsorption, primary transcription, virus maturation—all partial), several mechanisms of pathogenesis, aspects of the immune response, diagnosis, illness and treatment, epidemiology and vaccine development.
Research on the following areas is still in full flux and in part not generally accepted: several steps of the replication cycle (mechanism of viral entry into host cells, mechanisms of packaging and reassortment of viral RNAs, morphogenesis of subviral particles in viroplasms and maturation of virus particles in the rough endoplasmic reticulum (RER) with temporary acquisition and subsequent loss of an envelope), the true correlates of protection and the long-term effectiveness of RV vaccines.
Recently, a system that allows carrying out reverse genetics with some of the RV genes has been established which, however, has limitations. There is intensive research ongoing, which is trying to develop better and universally applicable reverse genetics systems. There is broad research on the molecular mechanisms of the immune response and on which immunological parameter correlates best with lasting protection from severe RV disease. Research into other than live attenuated vaccines is growing.
The establishment of better reverse genetics systems for RVs is the most important research goal for both the understanding of the molecular biology of RVs and the development of new and safe RV vaccines. The black boxes of our knowledge on aspects of RV replication (RNA packaging, RNA replication, control of reassortment and functions of the non-structural RV proteins) are under intensive research.
This article considers the process of re-classification of prescription drugs from prescription-only medications to over-the-counter (OTC) prescription drugs.
The recent change in classification for emergency contraception and simvastatin is explored in detail with similarities and differences being considered for a similar argument to be made for sildenafil.
The benefits for patients, physicians and other healthcare professionals are considered in detail.
We raise concerns about recently developed and existing patient group directions that, although extensive in their assessment, may omit to identify significant contributory factors which would necessitate appropriate medical intervention.
While the decision for re-classification to OTC would depend on a number of factors, we argue that, with the proviso of proper assessments being made, sildenafil should be made available as an OTC medication.
The safety and use of OTC medications for erectile dysfunction at a time when many first line prescription agents are reaching generic status.
Increasing numbers of medicines are being made available over the counter in the UK, by purchase in a pharmacy or from other less well-regulated outlets. When this is allowed by the Licensing Authority, it is often subject to certain restrictions. However, some drugs that could usefully be converted from prescription-only medicines (PoM status) to over-the-counter sales in a pharmacy (P status) are not suitable for full over-the-counter status, even with restrictions; and in some cases restrictions vitiate the usefulness of the medicine.
Drugs that can acceptably be switched from PoM status to P status include those that are used in the treatment of minor ailments or injuries, for health promotion or in palliative care.
However, not all drugs that are being switched fall into these categories. Ready availability of antimicrobial drugs over the counter, one of which (azithromycin) has recently been switched, could encourage the emergence of resistant organisms. Drugs that are used for long-term treatment and lifestyle drugs are also controversial, particularly if their adverse effects are of potential concern. On the other hand, the availability of many drugs via the internet removes the ability of regulators to control the supply of such drugs.
A new category of purchase, Pharmacist Consultation and Supply, with built-in safeguards, could improve the availability of some medicines under more careful control than is currently available for over-the-counter medicines.
Although several epidemiological studies demonstrate the association between resting heart rate (HR) and cardiovascular morbidity and mortality, an elevated HR remains a neglected cardiovascular risk factor.
This review summarizes the results of published studies on the relationship between elevated HR and cardiovascular risk.
The role of HR in myocardial ischaemia in coronary patients is well known. Experimental data and clinical observations support the importance of HR in the pathophysiology of atherosclerosis and plaque rupture. A large body of evidence points to high resting HR as a risk factor for mortality in various populations, including coronary patients.
HR reduction is suggested to be a mechanism explaining the prognostic benefit of beta-blockers after myocardial infarction or in heart failure patients. However, it was unclear whether HR reduction per se directly affects cardiovascular prognosis. Treatment with ivabradine, a pure HR-reducing agent, provides an opportunity to assess the effects of selectively lowering HR without altering other aspects of cardiac function.
The results of the recent Morbidity–Mortality Evaluation of the If Inhibitor Ivabradine in Patients with Coronary Disease and Left Ventricular Dysfunction study underline the importance of HR reduction in the management of stable coronary artery disease. The prospective analysis of data from the placebo arm demonstrated that elevated resting HR (≥70 bpm) is a strong independent predictor of clinical outcomes. Consistent with these data, ivabradine significantly improved coronary outcomes in patients with a HR of 70 bpm or more.
These data support the importance of HR in the management of stable coronary artery disease to assess prognosis and to guide optimal therapy.
Despite advances in knowledge and refinements of technique, the management of flexor tendon injuries within the digital sheath continues to present a formidable challenge. This in turn has led to a massive expansion in search of modified surgical therapies and various adjuvant therapies, which could prevent adhesion formation without compromising digital function.
A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords ‘tendon adhesion prevention’, ‘tendon healing’, ‘adhesion prevention in tendons’ and ‘adjuvants for adhesion prevention’. Studies detailing the use of surgical, pharmacological and non-pharmacological agents for adhesion prevention in digital flexor tendons were identified, and their bibliographies were thoroughly reviewed to identify further related articles. This search identified 41 studies, which investigated the use of various pharmacological agents in adhesion prevention in digital tendons.
There is a need to develop and utilize an optimal method for the prevention of adhesions in the flexor tendons of the hand, due to post-surgical complications.
Even though there have been significant advances in the prevention of adhesions in flexor tendons, it remains to be proved which, if any, of the current methods are the most beneficial.
The only thing that appears clinically justified in adhesion prevention is the need for early post-operative mobilization of digits after tendon injury or repair but the best method of mobilization remains controversial.
Suggested changes in surgical techniques and various proposed pharmacological and non-pharmacological modalities need to withstand the test of adequately powered human trials, before their justification for potential benefit in clinical practice is accepted.
Heavy exercise induces marked immunodepression, which is multifactorial in origin. Evidence showing clinical significance of this immunodepression is scarce.
We assessed in a systematic manner whether physical activity or intensity of exercise increase susceptibility to upper respiratory tract infections (URTI). A literature search was performed using the keywords ‘upper respiratory tract infections’, ‘athletes’, ‘exercise’ and ‘physical activity’. We considered all studies reporting of the effect of exercise, physical activity, sport and training on susceptibility to URTI. A total of 162 publications were identified and 30 studies were eligible (4 descriptive, 18 observational and 8 interventional). The 30 studies included 8595 athletes (5471 runners, 2803 swimmers) and 1798 non-athletes.
Moderate activity may enhance immune function, whereas prolonged, high-intensity exercise temporarily impairs the immune competence. Athletes, when compared with lesser active individuals, experience higher rate of URTI after training and competitions. In non-athletes, increasing physical activity is associated with a decreased risk of URTI.
The relationship between exercise and URTI is affected by poorly known individual determinants such as genetic factors, fitness, nutritional status or atopy. Elite athletes may have a decreased susceptibility to URTI.
The dose–response relationship between immunodepression and risk for URTI during the weeks following heavy exercise. What are the clinically relevant methods to assess exercise-induced immunodepression? Is down-regulation of immunity after intense exercise a protective response to limit inflammation? Is there a role for nutritional or pharmaceutical interventions to reduce risk of URTI?
The management of unstable slipped upper femoral epiphysis (SUFE) is controversial, with a high risk of developing avascular necrosis (AVN). We meta-analysed two areas of concern: reduction of the slip and the timing of treatment.
A search of Medline, CINAHL and Embase identified only retrospectively relevant studies: four regarding the role of reduction and five regarding the timing of treatment. The incidence of AVN was compared between reduced and unreduced SUFEs, and between those treated within 24 h of symptom onset and those treated thereafter.
Analysis of the pooled data gave an odds ratio of 2.20 (P = 0.290) in favour of the unreduced group, who had a lower risk of developing AVN. The odds ratio was 0.50 in favour of the group treated within 24 h from symptom onset (P = 0.441). However, though clinically important, these effects were not statistically significant.
The timing of treatment is somewhat inconsistent: two studies favour management more than 24 h after the onset of symptoms, while for three unstable SUFEs are best managed within 24 h.
Despite the non-significant results from the meta-analysis, it can be suggested that, if reduction is to be performed, it should be undertaken cautiously, as it may be associated with increased AVN. The ideal time for management of unstable slip is probably within 24 h of symptom onset.
There is a strong need for multicentre, randomized, controlled trials in this area.
The advent of AIDS brought about a group of patients unwilling to accept crucial aspects of the methodological standards for clinical research investigating Phase 1 drugs, surgeries or devices. Their arguments against placebo controls in trials, which depended—at the time—on the terminal status of patient volunteers led to a renewed discussion of the ethics of denying patients with catastrophic illnesses access to last-chance experimental drugs, surgeries or devices.
Existing ethics and health policy literature on the topic of access to experimental drugs.
The positions of those arguing for or against free access to experimental drugs for terminally ill patients are irreconcilable.
At stake are questions about the kinds of personal sacrifices society can reasonably expect patients in clinical trials to make to ensure statistically predictive results. These would benefit by necessity a much larger number of current and future patients—the conflict is about individual versus public interests. It is also about the question of whether or not the state can legitimately prevent patients with terminal illnesses from unfettered access to experimental drugs, surgeries or devices in order to motivate them to participate in clinical trials. We review the ethical arguments for and against the provision of access to Phase 1 agents for terminally ill patients.
Finding a compromise between providing free or no access to Phase 1 drugs for terminally ill patients.
We ought to investigate means to increase access to experimental drugs for terminally ill patients without sacrificing necessary clinical trials' sounds scientific methods.
Since many anti-cancer agents act by inflicting DNA damage on tumour cells, there is increasing interest in the use of inhibitors of DNA repair to increase the cytotoxicity of these agents. Poly(ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme that binds to sites of DNA damage and promotes repair by modifying a number of key proteins. Potent and specific inhibitors of PARP are available; these have been shown to increase the cytotoxicity of a range of anti-cancer agents including temozolomide, irinotecan and radiation.
Data from laboratory studies on human tumour cell lines, pre-clinical studies including tumour xenograft models and early phase clinical testing in human subjects are discussed.
Pre-clinical and early clinical testing indicates that PARP inhibitors are extremely well tolerated. As single agents they have activity against BRCA1- and BRCA2-deficient cancers, and in combination they increase the cytotoxic effects of certain chemotherapy agents.
In order for PARP inhibitors to improve outcomes for patients, their sensitizing effects must be tumour specific. Early clinical data indicate that systemic toxicity may be exacerbated, so future trials must address this issue. The mechanism of action of PARP inhibitors in combination with cytotoxic agents is also uncertain.
Among BRCA-deficient cancers, mechanisms of inherent and acquired resistance to PARP inhibitors are under investigation. Combining these agents with radiotherapy appears promising but designing clinical trials to test the efficacy and toxicity of this combination is problematic.
A particularly promising role for PARP inhibitors in the treatment of malignant brain tumours is outlined.
We conducted a systematic review of the current literature for this review, but as there are many gaps in the research literature, we have supplemented this by our own clinical experience.
There is a general agreement that Asperger syndrome (AS) is one of the autistic spectrum disorders, that it is a developmental disorder which is either present at birth or develops shortly after and that there is a strong hereditary component.
The fundamental impairment of AS is in the social arena, but what causes this is disputed. We propose that it is a disorder of non-verbal communication. Another important area of controversy is the extent to which AS may remit.
Many people with AS develop secondary psychiatric disorders in adolescence and adulthood, some of which may be linked genetically, notably bipolar disorder [DeLong R, Nohria C (1994) Psychiatric family history and neurological disease in autistic spectrum disorders. Dev Med Child Neurol, 36, 441–448] or be explicable by some other association, but many patients and carers attribute their anxiety and low mood to bullying. The prevalence, treatment and prevention of co-morbid mental health problems are rapidly developing areas of interest. Some people with AS are known to commit offences, and when they commit they are more likely to be violent offences against strangers. How much of a risk that is presented by people with AS, and how to assess this risk, is another growing area of concern.
The social impairments of people with AS include deficits in empathy, self-awareness and executive function. Many of these are quintessentially human characteristics, and the study of people with AS provides opportunities for using neuroimaging to compare people with AS and controls and identify which areas of the brain are concerned with these ‘higher functions’. The study of AS, like that of other fronto-striatal disorders, is also throwing light on the role of networks in the brain and on how networks are formed during embryogenesis.
The increasing number of available cardiac imaging techniques has made the investigation of coronary artery disease (CAD) more complex. Appropriate patient referral depends on an understanding of the pre-test likelihood of CAD and the information provided by each test.
This article describes myocardial perfusion scintigraphy (MPS) and summarizes evidence for its role in stable CAD and acute coronary syndromes with particular reference to current guidelines.
MPS has been extensively validated for the cost-effective diagnosis and prognosis of functionally significant CAD in both the acute and chronic settings. Its use is emphasized in the current NICE, national and international guidelines.
Although normal MPS is associated with good outcomes, assessments of subclinical atherosclerosis such as coronary artery calcium scoring and computed tomography coronary angiography (CTA) demonstrate that non-flow-limiting CAD remains prognostically important.
Technological developments, such as attenuation correction to improve diagnostic accuracy or analysis of left ventricular phase to detect dyssynchrony, carry the possibility of increasing the information that can be usefully gained from a single MPS study.
Of particular importance will be the role of MPS in an integrated imaging strategy that involves both anatomical and functional cardiac assessments. The use of hybrid technology that combines techniques such as MPS and CTA into a single imaging unit requires careful consideration with regard to diagnostic usefulness and cost-effectiveness.
Cardiac arrest is a common emergency in acute hospitals. The Resuscitation Council (UK) Advanced Life Support Guidelines provide a systematic approach to cardiac arrest recognition, treatment and aftercare. This review provides an update on the current treatment guidelines and identifies areas where these may be strengthened.
The evidence informing the 2005 Resuscitation Guidelines is reviewed. New evidence since the publication of the guidelines was identified by searching Medline (December 2005–December 2008) with the term heart arrest or advanced life support.
Opportunities for strengthening the chain of survival exist for each link. These include better recognition of critically ill patients at risk of cardiac arrest, improved quality of cardiopulmonary resuscitation, defibrillation strategies, which minimize pre- and post-shock pauses and development of post-resuscitation care bundles.
Emerging evidence suggests opportunities where Resuscitation Guidelines could be strengthened by focusing on specific aspects of the chain of survival.
Infection is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Research on CF infection has highlighted differences from other respiratory infections—both in the range and the nature of the organisms—especially in chronic infection. This is a rapidly advancing field of microbiology and is bringing insights into the complexity and adaptations of bacteria causing chronic infection in the respiratory tract.
The epidemiology of some infections in CF has changed, with reduction in spread of Burkholderia cenocepacia following patient segregation. Conversely, epidemic strains of Pseudomonas aeruginosa have emerged, which spread between patients; previously, most P. aeruginosa strains were patient-specific. Studies on hypermutators, quorum sensing, biofilm growth and the development of molecular identification have shed light on pathogenicity, microbial adaptation to the host and complexity of infection in CF. Non-tuberculous mycobacteria are emerging pathogens in CF; however, there is much to learn about pathogenicity and treatment of these infections. Species of aerobic and anaerobic bacteria, more commonly encountered in the upper tract, are found in significant numbers in CF sputum. The significance of this is however under debate. Finally, although the clinical relevance of conventional antibiotic susceptibility testing for chronic CF pathogens has been questioned, there are no clear alternatives.
Much has been learnt about pathogenicity, evolution of CF pathogens and development of antibiotic resistance. The need is to focus on clinical relevance of these observations to improve diagnosis, prevention and treatment of CF infection.
The current study provides an overview of history and evolution in total ankle arthroplasty.
We conducted a comprehensive literature search without limitations to language. Information from any source, providing evidence of the use ankle of prostheses (e.g. biomechanical testing, cadaveric implantations or clinical use) was evaluated. Data regarding biomechanical concepts, design considerations, published results (patient numbers, surgical method, follow-up, complications and survival rates) were collected.
Only level IV studies were found. Mobile-bearing prostheses are mainly used in Europe, and fixed-bearing implants are mainly used in the USA. The current designs' failure rate is 10–12% at ~5 years. Survival rates vary among different institutions. Increased surgeons' experience is associated with better outcomes.
Biomechanical studies and review of previous implant failures has led to the development of a new generation of implants.
Results show that ankle arthroplasty is a viable alternative for the management of ankle arthritis in selected patients.
Hepatitis C virus (HCV) is a major cause of liver disease worldwide. In industrialized countries, intravenous drug users (IDUs) are the main reservoir of infection. Relatively little information is available on HCV in the developing world.
Peer reviewed publications and presentations at major academic meetings.
HCV-related cirrhosis and death from hepatocellular carcinoma are likely to rise dramatically in the next three decades. Urgent intervention is required both to minimize the burden of disease in those already infected and to reduce the incidence of new infections, particularly in the IDU population.
Current models of care and commissioning in the UK and other countries do not adequately identify or treat HCV infection in IDUs. Most strategies focus on disease prevention and do not target new infections.
New models of care are currently being developed and validated.
The development of new models of HCV replication will transform our understanding and capacity to treat HCV infection.
Ultrasound is widely used for imaging purposes and as an adjunct to physiotherapy. Low-intensity pulsed ultrasound (LIPUS), having removed the thermal component found at higher intensities, is used to improve bone healing. However, its potential role in soft-tissue healing is still under investigation.
We searched on Medline using the keywords: low-intensity pulsed ultrasound, LIPUS and LIPUS and soft-tissue healing. Thirty-two suitable articles were identified.
Research, mainly pre-clinical, so far has shown encouraging result, with LIPUS able to promote healing in various soft tissues such as cartilage, inter-vertebral disc, etc. The effect on the bone-tendon junction, however, is primarily on bone. The role of LIPUS in treating tendinopathies is questionable. Adequately powered human studies with standardisation of intensities and dosages of LIPUS for each target tissue are needed.
Aicardi–Goutières syndrome (AGS) is an autosomal recessive encephalopathy characterized by acquired microcephaly, cerebral calcifications, leukodystrophy, cerebral atrophy and cerebrospinal fluid findings of chronic lymphocytosis and raised interferon-alpha (INF-alpha). The main extraneurological symptoms are chilblain-like skin lesions, usually on the fingers, toes and ears.
This review is based on a search of the published literature on AGS from 1984 onwards (particularly the most recent papers) and on knowledge and experience gained through the authors' work with the International Aicardi-Goutières Syndrome Association (IAGSA).
It is accepted that AGS can be mistaken for a congenital infection and that the diagnostic significance of its cardinal signs (raised INF-alpha levels, basal ganglia calcifications) is different in different stages of the disease. Currently, we know of four genes that, if mutated, can give rise to AGS, but at least one other gene is believed to exist. These genes are involved in the DNA damage response, a defect of which could provoke an inappropriate innate immune response, triggering increased secretion of INF-alpha, ultimately responsible for the main features of the disease.
The natural history of AGS has not yet been definitively described given the lack of extensive, long-term neuroradiological follow-up studies. Furthermore, it is not yet clearly understood how the innate immune system is activated, what triggers the onset of the disease or why it tends to ‘burn out’ after several months. Immunosuppressive therapy in the active stage of the disease does not seem to produce any real change in the clinical course, but more data are needed.
Current studies aim to clarify the molecular mechanisms underlying the pathogenesis of AGS and to establish the exact pathway by which retained nucleic acids activate the immune system. This knowledge could allow the development of therapeutic strategies.