UK epidemic strains of meticillin-resistant Staphylococcus aureus in clinical samples from Malta

Since 1999, the European Antimicrobial Resistance Surveillance System (EARSS) has monitored the rise in infection due to a number of organisms, including meticillin-resistant Staphylococcus aureus (MRSA). The EARSS reported that MRSA infections within intensive care units account for 25-50% of infections in many central and southern European countries, these included France, Spain, Great Britain, Malta, Greece and Italy. Each country has defined epidemic MRSA (EMRSA) strains; however, the method of spread of these strains from one country to another is unknown. In this current study, DNA profiles of 473 isolates of MRSA collected from the UK and Malta were determined by PFGE. Analysis of the data showed that two countries separated by a large geographical distance had a similar DNA profile pattern. Additionally it was demonstrated that strains of EMRSA normally found in the UK were also found in the Maltese cohort (EMRSA 15 and 16). A distinct DNA profile was found in the Maltese cohort, which may be a local EMRSA, and accounted for 14.4% of all Maltese isolates. The appearance of the same MRSA and EMRSA profiles in two separate countries suggests that MRSA can be transferred out of their country of origin and potentially establish in a new locality or country.

The UK obesity epidemic:new steering instruments for a new public policy problematic?

Since the 1980s UK government enthusiasm for market reforms has reconfigured the nature and scope of public services. Initially the marketisation of public services changed how public services were provided, increasingly market reforms and pro business policies have also modified the formation and understanding of public policy problematics and how they ought to be resolved. This is particularly noticeable when markets work imperfectly or even fail. UK governments have shown their reluctance to employ regulatory instruments to change the behaviour of companies preferring instead to make use of softer interventions, by focusing on providing advice for consumers and urging individuals to act responsibly. The dilemmas of this approach are explored by discussing the UK's former Labour government's (1997–2010) response to the increase in the incidence of obesity and related health complications.

Studies of the nature of Burkholderia cepacia in cystic fibrosis

Burkholderia cepacia is an opportunistic pathogen that colonises of the lungs of cystic fibrosis (CF) patients, with a frequently fatal outcome. Antibiotic resistance is common and highly transmissible epidemic strains have been described in the UK. 37 B. cepacia isolates from clinical and botanical sources were characterised via metabolic capabilities, antibiotic sensitivity, fatty acid methyl ester (FAME) profiles restriction digest analysis of chromosomal DNA by pulsed-gel electrophoresis (PFGE) (with the use of two separate restriction enzymes) and outer membrane protein (OMP) profiles. This revealed isolates of the UK CF epidemic strain to form a distinct group with a specific OMP profile. Cluster analysis of PFGE and FAME profiles revealed the species Burkholderia gladioli and Burkholderia vietnamiensis to be more closely related to each other and to laboratory strains of B. cepacia than to the CF epidemic strain considered a member of the latter species. The epidemic strain of B. cepacia may therefore be worthy of species definition in its own right. All the strains studied showed a high level of resistance to antibiotics, including the carbapenems. Considering this, carbapenemase production by isolates of B. cepacia was investigated. A metallo-β-lactamase from a clinical strain of B. cepacia was isolated and partially purified of using Cibacron blue F3GA-coupled agarose. The resulting preparation showed a single band of β-lactamase activity (pI 8.45) after analytical isoelectric focusing. The enzyme was particularly effective in the hydrolysis of imipenem. Meropenem, biapenem, cephaloridine, ceftazidime, benzylpenicillin, ampicillin and carbenicillin were hydrolysed at a lower rate. An unusual inhibition profile was noted. Inhibition by the metal ion chelators ethylene diamine tetra acetic acid and o-phenanthroline was reversed by addition of zinc, indicating a metallo-enzyme, whilst >90% inhibition was attainable with 0.1mM concentrations of tazobactam and clavulanic acid. A study of 8 other clinical isolates showed an enzyme of pI 8.45 to be present and inducible by imipenem in each case. This enzyme was assigned PCM-I (Pseudomonas cepacia metalloenzyme I).

Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.

Alzheimer's disease, a shifting paradigm in Spanish film:¿Y tú quién eres? And Amanecer de un sueño

In the last fifteen years Alzheimer's disease (AD) has changed the way in which developed countries have tended to perceive and deal with ageing. It has also become the main health problem needing to be resolved in both financial and social terms. If cancer was considered and labelled as the epidemic of the twentieth century, AD has soon been designated as the epidemic of the twenty-first century. This article analyses how AD is perceived and represented in two films, Amanecer de un sueño, directed in 2008 by Freddy Mas Franqueza, and ¿Y tú quién eres?, directed in 2007 by Antonio Mercero. As for ageing, questions of stigmatization and stereotyping around AD are discussed, and special consideration is given to the manner in which medical, social and political institutions in Spain have created a monolithic view of AD with the purpose of shaping a homogeneous social response to the disease. Current debates between those who perceive the disease as a social burden for the State and the family, and those who defend centring the discussion on the persons diagnosed with Alzheimer's disease and their personhoods frame the analysis of these two films. © W. S. Maney & Son Ltd 2013.

A comparison of the provision of the My Choice Weight Management Programme via general practitioner practices and community pharmacies in the United Kingdom

This study aimed to assess the effectiveness of a novel, community-based weight management programme delivered through general practitioner (GP) practices and community pharmacies in one city in the United Kingdom. This study used a non-randomized, retrospective, observational comparison of clinical data collected by participating GP practices and community pharmacies. Subjects were 451 overweight or obese men and women resident in areas of high socioeconomic deprivation (82% from black and minority ethnic groups, 86% women, mean age: 41.1 years, mean body mass index [BMI]: 34.5 kg m−2). Weight, waist circumference and BMI at baseline, after 12 weeks and after 9 months were measured. Costs of delivery were also analysed. Sixty-four per cent of participants lost weight after the first 12 weeks of the My Choice Weight Management Programme. There was considerable dropout. Mean percentage weight loss (last observation carried forward) was 1.9% at 12 weeks and 1.9% at final follow-up (9 months). There was no significant difference in weight loss between participants attending GP practices and those attending pharmacies at both 12 weeks and at final follow-up. Costs per participant were higher via community pharmacy which was attributable to better attendance at sessions among community pharmacy participants than among GP participants. The My Choice Weight Management Programme produced modest reductions in weight at 12 weeks and 9 months. Such programmes may not be sufficient to tackle the obesity epidemic.

Vaginal microbicides for the prevention of HIV transmission

The human immunodeficiency virus (HIV) kills more people worldwide than any other infectious disease. Approximately 42 million people, mostly in Africa and Asia, are currently infected with HIV (Figure 3.1), and 5 million new infections occur every year (AIDS Epidemic Update, 2002). It is estimated that 22 milIion people have died since the first clinical evidence of AIDS (acquired immunodeficiency syndrome) emerged in 1981 ('Mobilization for Microbicides' ~ The Rockfeller Foundation). HIV is generally transmitted in one of three ways: through unprotected sexual intercourse, blood-to-blood contact, and mother-to-child transmission. Once the virus has entered the body, it invades the cells of the immune system and initiates the production of new virus particles with concomitant destruction of the immune cells. As the number of immune cells in the body slowly declines, weight loss, debilitation, and eventually death occur due to opportunistic infections or cancers. Although AIDS is presently incurable, highly active antiretroviral therapy (HAART), where a cocktail of potent antiretroviral drugs are administered daily to HIV-positive patients to control the viral load, has resulted in dramatic reductions in HIV-related morbidity and mortality in the developed world

Synthesis and screening of potential antimicrobial compounds

Tuberculosis (TB), an infection caused by human pathogen Mycobacterium tuberculosis, continues to kill millions each year and is as prevalent as it was in the pre-antimicrobial era. With the emergence of continuously-evolving multi-drug resistant strains (MDR) and the implications of the HIV epidemic, it is crucial that new drugs with better efficacy and affordable cost are developed to treat TB. With this in mind, the first part of this thesis discusses the synthesis of libraries of derivatives of pyridine carboxamidrazones, along with cyclised (1,2,4-triazole and 1,2,4-oxadiazole) and fluorinated analogues. Microbiological screening against M. tuberculosis was carried out at the TAACF, NIAID and IDRI (USA). This confirmed the earlier findings that 2-pyridyl-substituted carboxamidrazones were more active than the 4-pyridyl-substituted carboxamidrazones. Another important observation was that upon cyclisation of these carboxamidrazones, a small number of the triazoles retained their activity while in most of the remaining compounds the activity was diminished. This might be attributed to the significant increase in logP value caused by cyclisation of these linear carboxamidrazones, resulting in high lipophilicity and decreased permeability. Another reason might be that the rigidity conferred upon the compound due to cyclisation, results in failure of the compound to fit into the active site of the putative target enzyme. In order to investigate the potential change to the compounds’ metabolism in the organism and/or host, the most active compounds were selected and a fluorine atom was introduced in the pyridine ring. The microbiological results shows a drastic improvement in the activity of the fluorinated carboxamidrazone amides as compared to their non fluorinated counterpart. This improvement in the activity could possibly be the result of the increased cell permeability caused by the fluorine. In a subsidiary strand, a selection of long-chain , -unsaturated carboxylic esters, -keto, -hydroxy carboxylic esters and -keto, -hydroxy carboxylic esters, structurally similar to mycolic acids, were synthesised. The microbiological data revealed that one of the open chain compound was active against the Mycobacterium tuberculosis H37Rv strain and some resistant isolates. The possible compound activity could be its potential to disrupt mycobacterial cell wall synthesis by interfering with the FAS-II pathway.

Medical error:a discussion of the medical construction of error and suggestions for reforms of medical education to decrease error

Introduction: There is a growing public perception that serious medical error is commonplace and largely tolerated by the medical profession. The Government and medical establishment's response to this perceived epidemic of error has included tighter controls over practising doctors and individual stick-and-carrot reforms of medical practice. Discussion: This paper critically reviews the literature on medical error, professional socialization and medical student education, and suggests that common themes such as uncertainty, necessary fallibility, exclusivity of professional judgement and extensive use of medical networks find their genesis, in part, in aspects of medical education and socialization into medicine. The nature and comparative failure of recent reforms of medical practice and the tension between the individualistic nature of the reforms and the collegiate nature of the medical profession are discussed. Conclusion: A more theoretically informed and longitudinal approach to decreasing medical error might be to address the genesis of medical thinking about error through reforms to the aspects of medical education and professional socialization that help to create and perpetuate the existence of avoidable error, and reinforce medical collusion concerning error. Further changes in the curriculum to emphasize team working, communication skills, evidence-based practice and strategies for managing uncertainty are therefore potentially key components in helping tomorrow's doctors to discuss, cope with and commit fewer medical errors.

Policy on the hoof:the handling of the foot and mouth disease outbreak in 2001

The foot and mouth disease (FMD) epidemic of 2001 was a disaster for sections of the agricultural industry, a number of businesses and for the Ministry of Agriculture, Fisheries and Food (MAFF), which met its demise as a government department during the crisis, being replaced by the Department of the Environment, Food and Rural Affairs (DEFRA). There were some 2,030 confirmed cases and over four million animals slaughtered. It caused the postponement of local elections and of a general election. From a public policy perspective it raised questions about contingency planning, the adjustment of policy to take account of change and how to manage a crisis. This article focuses on the background to the crisis and how it was handled.

Impact in contact lenses and the anterior eye:challenges prevailing in 2015

As we settle into a new year, this second issue of Contact Lens and Anterior Eye allows us to reflect on how new research in this field impacts our understanding, but more importantly, how we use this evidence basis to enhance our day to day practice, to educate the next generation of students and to construct the research studies to deepen our knowledge still further. The end of 2014 saw the publication of the UK governments Research Exercise Framework (REF) which ranks Universities in terms of their outputs (which includes their paper, publications and research income), environment (infrastructure and staff support) and for the first time impact (defined as “any effect on, change or benefit to the economy, society, culture, public policy or services, health, the environment or quality of life, beyond academia” [8]). The REF is a process of expert review, carried out in 36 subject-based units of assessment, of which our field is typically submitted to the Allied Health, Dentistry, Nursing and Pharmacy panel. Universities that offer Optometry did very well with Cardiff, Manchester and Aston in the top 10% out of the 94 Universities that submitted to this panel (Grade point Average ranked order). While the format of the new exercise (probably in 2010) to allocate the more than £2 billion of UK government research funds is yet to be determined, it is already rumoured that impact will contribute an even larger proportion to the weighting. Hence it is even more important to reflect on the impact of our research. In this issue, Elisseef and colleagues [5] examine the intriguing potential of modifying a lens surface to allow it to bind to known wetting agents (in this case hyaluronic acid) to enhance water retention. Such a technique has the capacity to reduced friction between the lens surface and the eyelids/ocular surface, presumably leading to higher comfort and less reason for patients to discontinue with lens wear. Several papers in this issue report on the validity of new high precision, fast scanning imaging and quantification equipment, utilising techniques such as Scheimpflug, partial coherence interferometry, aberrometry and video allowing detailed assessment of anterior chamber biometry, corneal topography, corneal biomechanics, peripheral refraction, ocular aberrations and lens fit. The challenge is how to use this advanced instrumentation which is becoming increasingly available to create real impact. Many challenges in contact lenses and the anterior eye still prevail in 2015 such as: -While contact lens and refractive surgery complications are relatively rare, they are still too often devastating to the individual and their quality of life (such as the impact and prognosis of patients with Acanthmoeba Keratitis reported by Jhanji and colleagues in this issue [7]). How can we detect those patients who are going to be affected and what modifications do we need to make to contact lenses and patient management prevent this occurring? -Drop out from contact lenses still occurs at a rapid rate and symptoms of dry eye seem to be the leading cause driving this discontinuation of wear [1] and [2]. What design, coating, material and lubricant release mechanism will make a step change in end of day comfort in particular? -Presbyopia is a major challenge to hassle free quality vision and is one of the first signs of ageing noticed by many people. As an emmetrope approaching presbyopia, I have a vested interest in new medical devices that will give me high quality vision at all distances when my arms won’t stretch any further. Perhaps a new definition of presbyopia could be when you start to orientate your smartphone in the landscape direction to gain the small increase in print size needed to read! Effective accommodating intraocular lenses that truly mimic the pre-presbyopic crystalline lenses are still a way off [3] and hence simultaneous images achieved through contact lenses, intraocular lenses or refractive surgery still have a secure future. However, splitting light reaching the retina and requiring the brain to supress blurred images will always be a compromise on contrast sensitivity and is liable to cause dysphotopsia; so how will new designs account for differences in a patient's task demands and own optical aberrations to allow focused patient selection, optimising satisfaction? -Drug delivery from contact lenses offers much in terms of compliance and quality of life for patients with chronic ocular conditions such as glaucoma, dry eye and perhaps in the future, dry age-related macular degeneration; but scientific proof-of-concept publications (see EIShaer et al. [6]) have not yet led to commercial products. Part of this is presumably the regulatory complexity of combining a medical device (the contact lens) and a pharmaceutical agent. Will 2015 be the year when this innovation finally becomes a reality for patients, bringing them an enhanced quality of life through their eye care practitioners and allowing researchers to further validate the use of pharmaceutical contact lenses and propose enhancements as the technology matures? -Last, but no means least is the field of myopia control, the topic of the first day of the BCLA's Conference in Liverpool, June 6–9th 2015. The epidemic of myopia is a blight, particularly in Asia, with significant concerns over sight threatening pathology resulting from the elongated eye. This is a field where real impact is already being realised through new soft contact lens optics, orthokeratology and low dose pharmaceuticals [4], but we still need to be able to better predict which technique will work best for an individual and to develop new techniques to retard myopia progression in those who don’t respond to current treatments, without increasing their risk of complications or the treatment impacting their quality of life So what will your New Year's resolution be to make 2015 a year of real impact, whether by advancing science or applying the findings published in journals such as Contact Lens and Anterior Eye to make a real difference to your patients’ lives?

The current drug treatment landscape for diabetes and perspectives for the future

The escalating global epidemic of type 2 diabetes mellitus has focused attention on the devastating consequences of protracted hyperglycemia. Early and effective intervention to control blood glucose is a fundamental principle of treatment guidelines, requiring assiduous use of current therapies. However, many patients do not achieve or maintain glycemic targets, emphasizing the need for further therapies. This narrative review assesses the available medicinal options to address hyperglycemia and the opportunities to develop novel agents.

Progmosis:evaluating risky individual behavior during epidemics using mobile network data

The possibility to analyze, quantify and forecast epidemic outbreaks is fundamental when devising effective disease containment strategies. Policy makers are faced with the intricate task of drafting realistically implementable policies that strike a balance between risk management and cost. Two major techniques policy makers have at their disposal are: epidemic modeling and contact tracing. Models are used to forecast the evolution of the epidemic both globally and regionally, while contact tracing is used to reconstruct the chain of people who have been potentially infected, so that they can be tested, isolated and treated immediately. However, both techniques might provide limited information, especially during an already advanced crisis when the need for action is urgent. In this paper we propose an alternative approach that goes beyond epidemic modeling and contact tracing, and leverages behavioral data generated by mobile carrier networks to evaluate contagion risk on a per-user basis. The individual risk represents the loss incurred by not isolating or treating a specific person, both in terms of how likely it is for this person to spread the disease as well as how many secondary infections it will cause. To this aim, we develop a model, named Progmosis, which quantifies this risk based on movement and regional aggregated statistics about infection rates. We develop and release an open-source tool that calculates this risk based on cellular network events. We simulate a realistic epidemic scenarios, based on an Ebola virus outbreak; we find that gradually restricting the mobility of a subset of individuals reduces the number of infected people after 30 days by 24%.

Exposing and addressing tobacco industry conduct in low-income and middle-income countries

The tobacco industry's future depends on increasing tobacco use in low-income and middle-income countries (LMICs), which face a growing burden of tobacco-related disease, yet have potential to prevent full-scale escalation of this epidemic. To drive up sales the industry markets its products heavily, deliberately targeting non-smokers and keeps prices low until smoking and local economies are sufficiently established to drive prices and profits up. The industry systematically flaunts existing tobacco control legislation and works aggressively to prevent future policies using its resource advantage to present highly misleading economic arguments, rebrand political activities as corporate social responsibility, and establish and use third parties to make its arguments more palatable. Increasingly it is using domestic litigation and international arbitration to bully LMICs from implementing effective policies and hijacking the problem of tobacco smuggling for policy gain, attempting to put itself in control of an illegal trade in which there is overwhelming historical evidence of its complicity. Progress will not be realised until tobacco industry interference is actively addressed as outlined in Article 5.3 of the Framework Convention on Tobacco Control. Exemplar LMICs show this action can be achieved and indicate that exposing tobacco industry misconduct is an essential first step.