Antonio Sánchez

A novel model of chronic wounds: importance of redox imbalance and biofilm-forming bacteria for establishment of chronicity.

Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼

Qualitative research within trials: developing a standard operating procedure for a clinical trials unit

25B/year in the US alone [1]. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.

Support and assessment for fall emergency referrals (SAFER 1) : cluster randomised trial of computerised clinical decision support for paramedics

BackgroundQualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design.MethodsHealth services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP).ResultsThe qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component.ConclusionsWe recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials.

Organizational culture and performance in health care for older people: a systematic review

Objective To evaluate effectiveness, safety and cost-effectiveness of Computerised Clinical Decision Support (CCDS) for paramedics attending older people who fall. Design Cluster trial randomised by paramedic; modelling. Setting 13 ambulance stations in two UK emergency ambulance services. Participants 42 of 409 eligible paramedics, who attended 779 older patients for a reported fall. Interventions Intervention paramedics received CCDS on Tablet computers to guide patient care. Control paramedics provided care as usual. One service had already installed electronic data capture. Main Outcome Measures Effectiveness: patients referred to falls service, patient reported quality of life and satisfaction, processes of care. Safety Further emergency contacts or death within one month. Cost-Effectiveness Costs and quality of life. We used findings from published Community Falls Prevention Trial to model cost-effectiveness. Results 17 intervention paramedics used CCDS for 54 (12.4%) of 436 participants. They referred 42 (9.6%) to falls services, compared with 17 (5.0%) of 343 participants seen by 19 control paramedics [Odds ratio (OR) 2.04, 95% CI 1.12 to 3.72]. No adverse events were related to the intervention. Non-significant differences between groups included: subsequent emergency contacts (34.6% versus 29.1%; OR 1.27, 95% CI 0.93 to 1.72); quality of life (mean SF12 differences: MCS −0.74, 95% CI −2.83 to +1.28; PCS −0.13, 95% CI −1.65 to +1.39) and non-conveyance (42.0% versus 36.7%; OR 1.13, 95% CI 0.84 to 1.52). However ambulance job cycle time was 8.9 minutes longer for intervention patients (95% CI 2.3 to 15.3). Average net cost of implementing CCDS was £208 per patient with existing electronic data capture, and £308 without. Modelling estimated cost per quality-adjusted life-year at £15,000 with existing electronic data capture; and £22,200 without. Conclusions Intervention paramedics referred twice as many participants to falls services with no difference in safety. CCDS is potentially cost-effective, especially with existing electronic data capture. Trial Registration ISRCTN Register ISRCTN10538608

09 Can older people who fall be identified in the ambulance call centre to enable alternative responses or care pathways

In recent years, there has been a growing understanding that organizational culture is an important characteristic that may influence the effectiveness of health care provision, not least for the growing numbers of older people needing care. The purpose of this paper is to review the literature to uncover any reliable evidence supporting the assertion that organizational culture in health care organizations is related, in terms of activity and outcome, to their performance. Searches identified 20 relevant papers published between 1993 and 2010. A number of studies reviewed claims to have uncovered evidence of a relationship in terms of activity, while others failed to find a clear relationship. None of the studies found much evidence against. In terms of outcomes, none of the studies reviewed found evidence of a relationship between culture and performance. It is clear that any relationship between culture and performance is highly unlikely to be simple: such relationships are more likely to be multiple, complex, contingent and dynamic.

Antimicrobial susceptibility and multilocus sequence typing of Mycoplasma capricolum subsp. capricolum

Background Older people who fall make up a substantial proportion of the 999 workload. They are a particularly vulnerable group who may benefit from referral to specialised community based falls services. This requires early identification, ideally from dispatch codes assigned in the ambulance call centre. Objective To assess the feasibility of using information given during 999 calls to identify older people who fall and who may benefit from an alternative response. Methods We examined all records of patients aged 65 years and over during 2008 in the Nottinghamshire area and identified those recorded as having fallen by attending crews. Dispatch codes were recorded for all cases and the utility of the dispatch code ‘Fall without priority symptoms’ (AMPDS 17) for identifying older people who had fallen was assessed. Results From 56 584 emergency (999) calls recorded, including 8119 for patients aged 65 years and over, 3246 (40%) cases were recorded as a fall. Of these, 2186 (67%) had been allocated AMPDS code 17 at dispatch (true positives), and 413 (13%) had not (false negatives), with 647 unknowns. Of 4871 cases not categorised as a fall by attending crews, 175 (4%) had been allocated an AMPDS code 17 (false positives), and 3315 (68%) had been given other codes (true negatives), with 1381 unknowns. The dispatch code AMPDS 17 had a sensitivity of 84% and a specificity of 95% for identifying falls compared with categorisation by crews. Limitations Definition of a fall is not always clear and there may be variations in usage of the category by crews. There was a high level of missing data in this study. Conclusion A large majority of older people who fall and for whom a 999 call is made can be identified in the ambulance call centre using dispatch codes. This provides a means for rapid and effective targeting of alternative responses to these patients, thereby potentially improving processes and outcomes of care.

04 Before the fall: a discussion paper on the organisational difficulties of setting up complex randomised control trials in emergency pre-hospital care

Mycoplasma capricolum subsp. capricolum is one of the causative agents of contagious agalactia (CA). Nevertheless, there is still a lack of information about its antimicrobial susceptibility and genetic characteristics. Therefore, the aim of this work was to study the antimicrobial and genetic variability of different Mycoplasma capricolum subsp. capricolum field isolates. For this purpose, the growth inhibition effect of 18 antimicrobials and a multilocus sequence typing (MLST) scheme based on five housekeeping genes (fusA, glpQ, gyrB, lepA and rpoB) were performed on 32 selected field isolates from Italy and Spain.The results showed a wide range of growth inhibitory effects for almost all the antimicrobials studied. Macrolides presented lower efficacy inhibiting Mcc growth than in previous works performed on other CA-causative mycoplasmas. Erythromycin was not able to inhibit the growth of any of the studied strains, contrary to doxycycline, which inhibited the growth of all of them from low concentrations. On the other hand, the study of the concatenated genes revealed a high genetic variability among the different Mcc isolates. Hence, these genetic variations were greater than the ones reported in prior works on other mycoplasma species.

Qualitative research within trials

Aim To describe unexpected challenges and strategies to overcome them when conducting a randomised control trial (RCT) of a computerised clinical decision support (CCDS) system for the triage of older fallers in emergency pre-hospital care. Background Few investigations have been conducted in of the emergency pre-hospital care using controlled, randomised, and prospective study designs. A review of 5842 Emergency Medical Services (EMS)-related research articles, published within the past 13 years revealed that fewer than 1% (n=54) were randomised, controlled trials. The paucity of randomised control trials in the pre-hospital care setting is largely due to difficulties in terms of obtaining informed consent, ethical approval, accurate data collection, and actual or perceived resistance to participation in research by busy emergency services. Setting We are conducting a Department of Health funded RCT (SAFER 1) to evaluate the effectiveness of CCDS which assists ambulance crews to assess and triage older fallers to appropriate care. The trial was planned in three UK ambulance services, in collaboration with local clinicians based within hospitals, primary care and falls services. Study progress SAFER1 has suffered numerous delays and has had to seek two funding extensions, the latest until 2010. Delays have related to 1) ambulance service reorganisation in England 2) planned and actual (although delayed) implementation of a new electronic patient record in most English services 3) performance pressures 4) internal restructuring of partner services. Discussion Major modifications of the project timescales and research partners were precipitated by these factors as well as with difficulties in engaging non-research organisations with research protocols, methods and thinking. However, the greatest barriers as well as the greatest facilitation in the implementation of this trial were found to be at the inter-organisational level. We are slowly overcoming these barriers by conducting research that is consistent with corporate administrative systems and by identifying and working closely with key personnel in a flexible way. Our experience leads us to believe that prior to starting a complex trial of this nature, the implementation team should undertake a thorough analysis of the organisational context in which the trial is going taking place. Organisational cultures which are conducive and supportive of research should not be the goal of RCTs, but analysis of organisational and team cultures prior to the trial set up would assist in devising strategies to determine the research process. Clear guidelines for pre hospital care research are urgently needed which encourage this practice.

Zoonoses in Veterinary Students: A Systematic Review of the Literature.

BackgroundQualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design.MethodsHealth services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP).ResultsThe qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component.ConclusionsWe recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials.

A2 The potential and pitfalls of anonymised data linkage for follow-up of patient outcomes in prehospital emergency care research

Background Veterinary students face diverse potential sources of zoonotic pathogens since the first years of their academic degree. Such sources include different animal species and pathologic materials which are used at university facilities as well as commercial clinics, farms and other external facilities. Objectives The present study utilizes a systematic review of the literature to identify zoonoses described in veterinary students. Data sources Web of Science and PubMed. Results Of the 1,254 titles produced by the bibliographic search, 62 were included in this review. Whereas 28 of these articles (45.2%) described individual cases or outbreaks, the remaining 34 (54.8%) reported serological results. The zoonotic etiological agents described were bacteria, in 39 studies (62.9%), parasites, in 12 works (19.4%), virus, in 9 studies (14.5%) and fungi, in 2 (3.2%) of the selected articles. The selected literature included references from 24 different countries and covered the time period of the last 55 years. Limitations The fact that common cases of disease or cases of little clinical importance without collective repercussions are not usually published in peer-reviewed journals limits the possibility to reach conclusions from a quantitative point of view. Furthermore, most of the selected works (66.1%) refer to European or North American countries, and thus, the number of cases due to pathogens which could appear more frequently in non-occidental countries might be underestimated. Conclusions/implications The results of the present systematic review highlight the need of including training in zoonotic diseases since the first years of Veterinary Science degrees, especially focusing on biosecurity measures (hygienic measures and the utilization of the personal protective equipment), as a way of protecting students, and on monitoring programs, so as to adequately advise affected students or students suspicious of enduring zoonoses.