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The White Bird Passes is an autobiographical novella published in 1958 by Scottish writer, playwright, and poet Jessie Kesson. Born in a workhouse in 1916, she lived in a back lane slum in Elgin until she was eight, when her single mother was judged to be unfit, and Jessie was sent to an orphanage. There she received a basic education, showing sufficient promise for a university place to be discussed. She later referred to this time as 'the golden years'.

Background Hydrocephalus is managed by surgically implanting flow-diversion technologies such as differential pressure valves and antisiphoning devices; however, such hardware is prone to failure. Extensive research has tested them in flow-controlled settings using saline or de-aerated water, yet little has been done to validate their performance in a setting recreating physiologically relevant parameters, including intracranial pressures, cerebrospinal fluid (CSF) protein content, and body position. Objective To more accurately chart the episodic drainage characteristics of flow-diversion technology. A gravity-driven benchtop model of flow was designed and tested continuously during weeks-long trials. Methods Using a hydrostatic pressure gradient as the sole driving force, interval flow rates of 6 valves were examined in parallel with various fluids. Daily trials in the upright and supine positions were run with fluid output collected from distal catheters placed at alternating heights for extended intervals. Results Significant variability in flow rates was observed, both within specific individual valves across different trials and among multiple valves of the same type. These intervalve and intravalve variabilities were greatest during supine trials and with increased protein. None of the valves showed evidence of overt obstruction during 30 d of exposure to CSF containing 5 g/L protein. Conclusion Day-to-day variability of ball-in-cone differential pressure shunt valves may increase overdrainage risk. Narrow-lumen high-resistance flow control devices as tested here under similar conditions appear to achieve more consistent flow rates, suggesting their use may be advantageous, and did not demonstrate any blockage or trend of decreasing flow over the 3 wk of chronic use.

The relationship between crime and gambling is well established; however, few studies have examined offending specifically to finance gambling within a UK gambling treatment-seeking population. A total of 1226 treatment-seeking gamblers completed the Problem Gambling Severity Index (PGSI), Patient Health Questionnaire and the Generalized Anxiety Disorder 7 item scale, and were asked whether they had committed any illegal behaviours to finance gambling. A total of 42.5% reported offending behaviour. A greater proportion of the offending group was single or married/cohabiting, had a lower level qualifications, lower income, had experienced childhood abuse, family mental health problems and gambling-related harms compared with the non-offending group. Offenders reported higher anxiety, depression and disordered gambling scores. Disordered gamblers who offend make up a discrete and complex subgroup with distinct vulnerabilities. Findings will be useful to clinicians involved in the assessment and management of problematic gambling. Gamblers who offend to finance gambling may have different treatment needs and treatment providers should administer appropriate clinical interventions to address vulnerabilities.

False negative culture results in periprosthetic joint infection (PJI) are not uncommon particularly when patients have received long term antibiotics. Polymerase chain reaction (PCR) has a lower specificity partly due to detection of residual DNA from dead bacteria. Propidium monoazide (PMA) prevents DNA from dead bacteria from being amplified during the PCR. This study aimed to determine the role of PMA in PCR for diagnosis of PJI. Clinical samples were tested by PCR with and without prior treatment with PMA and compared to conventional microbiological culture. The PCR assay included genus-specific primers for staphylococci and enterococci and species-specific primers forCutibacterium acnes.The validated conditions of PMA treatment used in this study were 20 μM concentration and 5 and 10 min of dark incubation and photo-activation respectively. 202 periprosthetic tissues and explanted prostheses from 60 episodes in 58 patients undergoing revision arthroplasties for either PJI or non-infective causes were tested, by culture, PCR, and PMA-PCR. 14 of the 60 episodes satisfied the Musculoskeletal Infection Society (MSIS) criteria for PJI and 46 did not. Sensitivity of culture, PCR, and PMA-PCR were 50%, 71%, and 79% respectively. Specificities were 98%, 72%, and 89% respectively. All figures were calculated for episodes rather than samples. PMA-PCR enhanced both the specificity and the sensitivity of PCR. It has the potential to detect residual bacterial viability prior to reimplantation in the two-stage revision for PJI.

The paper describes a treatment pilot for gambling and compulsive addiction within an NHS problem gambling clinic. The pilot study used a brief relational psychodynamic treatment protocol specifically designed to meet the needs of a group of patients who had not responded to CBT and who had other addictions or co- morbidities. Seventy two (n= 72) patients were offered 12 sessions of therapy by four psychodynamic counsellors. Results were assessed using pre and post treatment PHQ- 9, GAD- 7 and PGSI scores. Weekly feedback and supervision from counsellors and patients was used to assess the treatment model. The results highlighted that the Psychodynamic Addiction Model (PAM) was associated with reduced depression (Mean=14.9; SD 6.7), anxiety (Mean=11.5; SD 5.9) and gambling severity (p < .001), suggesting that a relational psychodynamic treatment is needed for complex patients with compulsive addiction, where CBT had not been successful. These results also highlight the importance of the therapeutic relationship as a critical factor in the treatment of patients with compulsive addiction problems.

Two major complications of indwelling urinary catheterisation include infection and mineral encrustation of the catheter. Our antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin has demonstrated long-term protective activity against major uropathogens. This study aimed to firstly assess the ability of the AUC to resist mineral encrustation in the presence and absence of bacteria. Secondly, it aimed to investigate the AUC’s anti-biofilm activity against multi-drug resistant organisms. There was no difference in surface roughness between AUC and control segments. In a static and a perfusion model, phosphate deposition was significantly reduced on AUCs challenged with P. mirabilis. Furthermore, none of the AUCs blocked during the 28 day test period, unlike controls. The AUC prevented colonisation by methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, extended-spectrum beta-lactamase producing E. coli, and carbapenemase-producing E. coli for 12 consecutive weekly challenges. All three drugs impregnated into the catheter continued to exert protective activity throughout 12 weeks of constant perfusion. The drugs appear to migrate into the crystalline biofilm to continually protect against bacteria not it direct contact with the catheter surface. In conclusion, the AUC reduces mineral encrustation and may increase time to blockage in the presence of P. mirabilis, and does not predispose to mineral deposition under other conditions. It also offers 12 weeks of protection against multi-drug resistant bacteria. Statement of significance Infection and associated mineral encrustation of urinary catheters are two serious complications of indwelling urinary catheters. Others have attempted to address this through various technologies such as coatings, dips, and surface modifications to prevent infection and/or encrustation. However, all current ‘anti-infective’ urinary catheter technologies are limited to short-term use. Some patients with spinal injuries, multiple sclerosis, stroke survivors and others use long-term catheters for 4–12 weeks at a time with multiple catheterisation possibly throughout the rest of their life. We present a urinary catheter for long-term use that is impregnated with three antimicrobials by a patient-protected process to prevent infection and encrustation for up to 12 weeks, the maximum lifetime of a long-term catheter before it is changed.

BackgroundThe first step in bundle design or implementation is to identify the problem being addressed. Several validated approaches are recommended to facilitate this. These include using systematic reviews, adverse event triggers and risk assessment tools. However, these methods do not fully take the local context into account, which will limit the effectiveness of the bundle.AimThis study explores the potential benefit of using a comprehensive audit to identify an organisation’s local context prior to designing and implementing a care bundle.MethodA comprehensive audit comprising observations of four patient journeys, interviews with 21 staff and clinical data was carried out at one large National Health Service trust in England. A patient warming care bundle was used as the exemplar.FindingsEach of the three data collection methods identified specific local practices which would be addressed within the planning and implementation stages of a care bundle. These practices would not have been identified through other recommended methods.ConclusionA comprehensive audit, comprising observations, interviews and clinical data is a successful method to identify local contextual issues prior to care bundle implementation.

The rising occurrence of antimicrobial resistance demands new strategies for delivering antibiotics to ensure their effective use. In this study, a multi-functional strategy to address medical device associated infections is explored whereby an anti-attachment and an antibacterial mechanism have been combined. Silicone catheters impregnated with multiple antibiotics are coated with polyacrylate coatings previously shown to reduce bacterial attachment and biofilm formation. Antibiotics are delivered through the applied coating and the delivery rate depends on the coating thickness and the calculated log P. Coated devices achieve a zone of inhibition and TK100 to Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus similar to those of uncoated devices, whilst maintaining anti-attachment properties. No adverse immunological responses of the coatings were observed. The multi-functional nature of the device developed in the study represents an important approach to combatting medical device associated infections.

© 2018 Wiley Periodicals, Inc. Aims: We have developed a novel antimicrobial urinary catheter (AUC) impregnated with rifampicin, triclosan, and sparfloxacin and demonstrated that it has long-term (∼84 days) protection against bacterial colonization in vitro. This study aimed to assess the safety and patient acceptability of this device in long-term catheter users. Methods: Adults who use long term (>28 days) indwelling urinary catheters with capacity to consent were invited to receive the AUC at their next catheter change. The primary outcome measure was adverse events (AE) attributable to antimicrobial impregnation of the catheter. Secondary outcome measures included severity of related AEs, patient acceptability, early removal of the trial catheter, and degree of microbial colonization of trial catheters. Except for the last, outcomes were assessed by telephone interviews. Original and trial catheters were collected, and the lumens and balloons were separated and analyzed for microbiological colonization. Results: Thirty participants were recruited. Eighty four AEs were reported, and only one was rated as “probably” related to antimicrobial impregnation. The AE was mild and resolved within 48 h. A total of 82.14% of participants rated the catheter as no different or better than their usual catheter. Two participants chose to remove the AUC early due to it feeling shorter. There were significantly fewer bacterial isolates attached to the balloons of trial catheters compared to the matched original catheters. Conclusions: The AUC has an advantageous safety profile and was acceptable to the majority of participants. Information gained from this trial will support a larger randomized controlled study of efficacy.

Objectives To evaluate potential anti-biofilm agents for their ability to enhance the activity of antibiotics for local treatment of localized biofilm infections. Methods Staphylococcus aureus and Pseudomonas aeruginosa in vitro biofilm models were developed. The putative antibiotic enhancers N-acetylcysteine, acetylsalicylic acid, sodium salicylate, recombinant human deoxyribonuclease I, dispersin B, hydrogen peroxide and Johnson’s Baby Shampoo (JBS) were tested for their anti-biofilm activity alone and their ability to enhance the activity of antibiotics for 7 or 14 days, against 5 day old biofilms. The antibiotic enhancers were paired with rifampicin and clindamycin against S. aureus and gentamicin and ciprofloxacin against P. aeruginosa. Isolates from biofilms that were not eradicated were tested for antibiotic resistance. Results Antibiotic levels 10× MIC and 100× MIC significantly reduced biofilm, but did not consistently eradicate it. Antibiotics at 100× MIC with 10% JBS for 14 days was the only treatment to eradicate both staphylococcal and pseudomonal biofilms. Recombinant human deoxyribonuclease I significantly reduced staphylococcal biofilm. Emergence of resistance of surviving isolates was minimal and was often associated with the small colony variant phenotype. Conclusions JBS enhanced the activity of antibiotics and several other promising anti-biofilm agents were identified. Antibiotics with 10% JBS eradicated biofilms produced by both organisms. Such combinations might be useful in local treatment of localized biofilm infections.

Amniotic membrane (AM) is used to treat a range of ophthalmic indications but must be presented in a non-contaminated state. AM from elective caesarean sections contains natural microbial contamination, requiring removal during processing protocols. The aim of this study was to assess the ability of antibiotic decontamination of AM, during processing by innovative low-temperature vacuum-drying. Bioburden of caesarean section AM was assessed, and found to be present in low levels. Subsequently, the process for producing vacuum-dried AM (VDAM) was assessed for decontamination ability, by artificially loading with Staphylococcus epidermidis at different stages of processing. The protocol was highly efficient at removing bioburden introduced at any stage of processing, with antibiotic treatment and drying the most efficacious steps. The antibacterial activity of non-antibiotic treated AM compared to VDAM was evaluated using minimum inhibitory/biocidal concentrations (MIC/MBC), and disc diffusion assays against Meticillin-resistant Staphylococcus aureus, Meticillin-resistant S. epidermidis, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. Antibacterial activity without antibiotic was low, confirmed by high MIC/MBC, and a no inhibition on agar lawns. However, VDAM with antibiotic demonstrated effective antibacterial capacity against all bacteria. Therefore, antibiotic decontamination is a reliable method for sterilisation of AM and the resultant antibiotic reservoir is effective against gram-positive and –negative bacteria.

One of the main difficulties faced in treating gambling disorder is compliance with psychological treatment. Gambling takes many forms and can differ greatly in its features such as speed of play and skill requirements. The type of gambling a pathological gambler opts for may play a key role in treatment compliance. The aim of the present study was to determine whether within treatment seeking sample of gambling disorder clients, gambling activity has any correlation with their resultant treatment outcomes. The study incorporated 524 treatment-seeking individuals who are clients of the National Problem Gambling Clinic in London. All of the clients were assessed prior to treatment and fulfilled the Problem Gambling Severity Index criteria for problem gambling. Data concerning clients' gambling behavior over the previous year was gathered using self-reports. Subsequently, the data was fitted to a multinomial logistic regression model, with the treatment outcome (i.e. pre-treatment dropouts, during treatment dropouts, and completed treatment) as the dependent variable and gambling behavior as the independent variable, whilst controlling for socio-demographic factors. The use of gaming machines was a significant predictor of dropping out pre-treatment (p

Background\ud \ud The insertion of external ventricular drains (EVDs) is necessary in some neurosurgical patients, but increases the risk of meningitis/ventriculitis. While there are well-recognized risk factors, the proportion of patients who develop meningitis/ventriculitis varies partly due to differences in definitions. A multi-disciplinary working group was established to agree definitions for EVD-associated meningitis/ventriculitis, and a surveillance system was piloted in four centres in the UK and Ireland.\ud \ud Methods\ud \ud Definitions were agreed based on those published previously and on clinical and microbiological criteria. An agreed dataset was developed to monitor patients after the insertion of an EVD and until the EVD was removed and the microbial aetiology was recorded.\ud \ud Findings\ud \ud Four neurosurgical centres participated, with 61–564 patients surveyed in each unit. The vast majority of drains were cranial. Intracranial haemorrhage was the most common indication for the EVD insertion. Between 6% and 35% of EVDs were inserted by consultants rather than junior doctors. The proportion of patients who developed meningitis/ventriculitis varied from 3% to 18% and from 4.8 to 12.7/1000 EVD-days. Coagulase-negative staphylococci were the most common microbial causes.\ud \ud Conclusions\ud \ud Routine and ongoing monitoring of patients with an EVD in situ to detect meningitis/ventriculitis presents logistical difficulties, and few units do so. This pilot study suggests that a national system of surveillance with agreed definitions and a methodology to enable unit-to-unit comparisons of EVD meningitis/ventriculitis is both necessary and feasible. This will, in turn, inform quality improvement processes leading to the minimization of infection.

ObjectivesTo determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores.DesignCross-sectional electronic survey.SettingEmergency departments (EDs) (n=112) in the UK and Ireland.ParticipantsEmergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019.Main outcome measureNFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery.ResultsThe median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5–90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%–50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%–75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%–100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9).ConclusionHigher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible.

Background External ventricular drainage (EVD) carries a high risk of ventriculitis, increasingly caused by MDR Gram-negative bacteria such as Escherichia coli and Acinetobacter baumannii. Existing antimicrobial EVD catheters are not effective against these, and we have developed a catheter with activity against MDR bacteria and demonstrated the safety of the new formulation for use in the brain. Objectives Our aim was to determine the ability of a newly formulated impregnated EVD catheters to withstand challenge with MDR Gram-negative bacteria and to obtain information about its safety for use in the CNS. Methods Catheters impregnated with three antimicrobials (rifampicin, trimethoprim and triclosan) were challenged in flow conditions at four weekly timepoints with high doses of MDR bacteria, including MRSA and Acinetobacter, and monitored for bacterial colonization. Catheter segments were also inserted intracerebrally into Wistar rats, which were monitored for clinical and behavioural change, and weight loss. Brains were removed after either 1 week or 4 weeks, and examined for evidence of inflammation and toxicity. Results Control catheters colonized quickly after the first challenge, while no colonization occurred in the impregnated catheters even after the 4 week challenge. Animals receiving the antimicrobial segments behaved normally and gained weight as expected. Neurohistochemistry revealed only surgical trauma and no evidence of neurotoxicity. Conclusions The antimicrobial catheter appears to withstand bacterial challenge for at least 4 weeks, suggesting that it might offer protection against infection with MDR Gram-negative bacteria in patients undergoing EVD. It also appears to be safe for use in the CNS.

© 2015 Published by Elsevier B.V. Catheter-associated urinary tract infection (CAUTI) is the commonest hospital-acquired infection, accounting for over 100,000 hospital admissions within the USA annually. Biomaterials and processes intended to reduce the risk of bacterial colonization of the catheters for long-term users have not been successful, mainly because of the need for long duration of activity in flow conditions. Here we report the results of impregnation of urinary catheters with a combination of rifampicin, sparfloxacin and triclosan. In flow experiments, the antimicrobial catheters were able to prevent colonization by common uropathogens Proteus mirabilis, Staphylococcus aureus and Escherichia coli for 7 to 12 weeks in vitro compared with 1-3 days for other, commercially available antimicrobial catheters currently used clinically. Resistance development was minimized by careful choice of antimicrobial combinations. Drug release profiles and distribution in the polymer, and surface analysis were also carried out and the process had no deleterious effect on the mechanical performance of the catheter or its balloon. The antimicrobial catheter therefore offers for the first time a means of reducing infection and its complications in long-term urinary catheter users.

Introduction Infectious conditions of the middle ear are a common and significant cause of morbidity and mortality worldwide. Systemic antibiotics are frequently used, but their effectiveness will depend on whether an adequate antibiotic concentration is achieved in the middle ear; this is especially important in biofilm infections such as otitis media with effusion (OME), where high antibiotic concentrations are typically required for effective treatment. Objective This review examines what antibiotic levels can be reached in the middle ear with oral administration, as a means of guiding rational antibiotic choice in the clinic and future research, and to determine whether levels high enough for biofilm eradication are reached. Methods A literature search of studies measuring levels of antibiotics in the plasma and in the middle ear after oral administration was conducted. These levels were compared to the minimum inhibitory concentrations (MIC) provided by the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to determine if antibiotic doses were reaching sufficient levels to inhibit planktonic bacteria. The middle ear concentrations were then calculated as a multiple of the MIC to determine if the concentrations were reaching biofilm eradication concentrations (typically up to 1000 × MIC). Results The highest antibiotic levels against Staphylococcus aureus reach 8.3 × MIC, against Moraxella catarrhalis 33.2 × MIC, against Haemophilus influenzae 31.2 × MIC, and against Streptococcus pneumoniae 46.2 × MIC. The macrolide antibiotics reach higher levels in the middle ear than in plasma. Conclusions Orally administered antibiotics reach levels above the MIC in the middle ear. However, they do not reach levels that would be likely to eradicate biofilms.

Urinary tract infections (UTIs) account for the majority of hospital-acquired infections (HAI), and most of these occur in catheterized patients. However, for most the presence of bacteria in the urine (bacteriuria) is asymptomatic, yet in many institutional and national surveillance studies it is still attributed as ‘infection’. Although guidance is that only symptomatic UTI should be treated, except in pregnancy, bacteriuria in catheterized patients is frequently overinvestigated and antibiotics overused. Most infections are caused by enteric bacteria such as Escherichia coli, but other bacteria such as Proteus mirabilis and staphylococci are more prominent in HAI. Aseptic technique for catheter insertion and during subsequent catheter care together with minimizing catheter duration are very important to prevent catheter-associated UTI (CAUTI). Prophylactic antibiotics should be avoided. National and international action to adopt evidence-based consensus protocols for management of catheterized patients and judicial use of antimicrobial chemotherapy promise to be of greatest benefit.

Infections associated with percutaneous pins and wires are common complications which can have a significant impact on patient outcomes. A survey was undertaken to identify current practice and gain insight into variations of clinical practice. Invitations were sent by email to complete an electronic questionnaire using SurveyMonkey. The survey was left open for 100 days. The single largest group of respondents (37.4%, n = 120) cleansed pin sites daily, with significant differences identified between medical and nursing professions (P = 0.02), and country of practice (P < 0.001). Significant differences were also identified in the use of different cleansing solutions between medical and nursing professions (P < 0.001) and country (P < 0.001). The majority group preferences were saline 30% (n = 96) and alcoholic chlorhexidine 29.6% (n = 95). Pin site crusts were routinely removed by 57.9% (n = 186). Pin sites were left exposed by 50.3% (n = 160). Dry gauze was identified as the most common dressing used to dress pin sites, however, substantial variation was identified in the types of dressings used. Compression was not routinely applied to pin sites by 51.6% (n = 165). There remains considerable diversity of practice when caring for pin sites. Further research is required to identify the most effective methods in preventing pin site infection.

Grounded in Lazarus’ (1999) Cognitive Motivational Relational Theory of Emotions and informed by Courneya and Carron’s (1992) Game Location Framework, this study examined the influence of stress and emotions on the decision-making of UK association football referees who were refereeing at different competitive levels. Through the use of interviews, it was found that stressors emanating from the crowd, previous mistakes, confrontation, players with bad reputations, and assessors evaluating referee performance was associated with threat or harm stress appraisals. These appraisals were associated with negative emotions that, when not managed, influenced poor perceived decision-making. In particular, the amateur referees reported situations where they were not able to cope with the stress and negative emotions experienced, and displayed either counter-attacking decision-making through giving decisions against the offending player, coach or team, or incorrect decisions due to a lack of focus caused by anxiety. In comparison, professional referees demonstrated problem-focused and emotion-focused coping strategies that promoted better decision-making. Implications for referee development are provided, as are recommendations for future research.

Hydrocephalus, a condition in which the structure of the brain is distorted and its blood supply curtailed, is caused by accumulation of cerebrospinal fluid (CSF), usually the result of obstruction. Temporary management of the raised pressure involves the insertion of a catheter into the ventricles and drainage of CSF into a bag at the bedside external ventricular drainage (EVD). Long-term management is accomplished by the insertion of a shunt, consisting of a silicone catheter and a valve to control the rate and direction of flow, draining CSF into a body cavity, usually the abdomen. Infection involving the shunt or EVD catheters is a major complication. Bacterial biofilm development inside the catheters leads to failure of antibiotic treatment and removal of the device. Many attempts have been made to reduce the rate of infection, but recently antimicrobial catheters have been used with some success. The key to this is the use of an impregnation process rather than a coating, the former allowing maintenance of a fully active antimicrobial boundary layer for many days in flow conditions. Clinically predictive in vitro evaluation of antimicrobial catheters is demanding and expensive. Clinical experience with antimicrobial shunts shows their benefit, but there is insufficient experience with antimicrobial EVDs to confirm the early promising findings.

Objective Otitis media with effusion (OME), a common chronic childhood condition affecting hearing, is thought to be a result of bacterial infection, with biofilms recently implicated. Although bacterial DNA can be detected by polymerase chain reaction in 80% of patients, typically fewer than half of effusions are positive using standard culture techniques. We adopted an alternative approach to demonstrating bacteria in OME, using a bacterial viability stain and confocal laser scanning microscopy (CLSM): staining allows detection of live bacteria without requiring growth on culture, while CLSM allows demonstration of the three-dimensional structure typical of biofilms. Methods Effusion samples were collected at the time of ventilation tube insertion, analysed with CLSM and bacterial viability stain, and extended culture techniques performed with the intention of capturing all possible organisms. Results Sixty-two effusions (42 patients) were analysed: 28 (45.2%) were culture-positive, but 51 (82.3%) were CLSM-positive. Combining the two techniques demonstrated live bacteria in 57 (91.8%) samples. Using CLSM, bacteria exhibited biofilm morphology in 25 effusions and were planktonic in 26; the proportion of samples exhibiting biofilm morphology was similar in the culture-positive and culture-negative groups (50.0% and 48.3%, respectively). Biofilm samples contained an average of 1.7 different bacterial isolates and planktonic samples 2.0, with the commonest bacteria identified being coagulase-negative staphylococci. Conclusion Live bacteria are present in most effusions, strongly suggesting that bacteria and biofilms are important in the aetiopathogenesis of OME.

Cerebrospinal fluid (CSF) shunts used to treat hydrocephalus have an overall infection rate of about 10% of operations. The commonest causative bacteria are Staphylococcus epidermidis , followed by Staphylococcus aureus and enterococci. Major difficulties are encountered with nonsurgical treatment due to biofilm development in the shunt tubing and inability to achieve sufficiently high CSF drug levels by intravenous administration. Recently, three cases of S. epidermidis CSF shunt infection have been treated by intravenous linezolid without surgical shunt removal, and we therefore investigated vancomycin and linezolid against biofilms of these bacteria in vitro . A continuous-perfusion model of shunt catheter biofilms was used to establish mature (1-week) biofilms of Staphylococcus aureus , Staphylococcus epidermidis (both methicillin resistant [MRSA and MRSE]), Enterococcus faecalis , and Enterococcus faecium . They were then “treated” with either vancomycin or linezolid in concentrations achievable in CSF for 14 days. The biofilms were then monitored for 1 week for eradication and for regrowth. Enterococcal biofilms were not eradicated by either vancomycin or linezolid. Staphylococcal biofilms were eradicated by both antibiotics after 2 days and did not regrow. No resistance was seen. Linezolid at concentrations achievable by intravenous or oral administration was able to eradicate biofilms of both S. epidermidis (MRSE) and S. aureus (MRSA). Neither vancomycin at concentrations achievable by intrathecal administration nor linezolid was able to eradicate enterococcal biofilms. It is hoped that these in vitro results will stimulate further clinical trials with linezolid, avoiding surgical shunt removal.

Substituted tetrahydropyrans, spiroethers and spiroketals can be prepared in a single step using the ISMS reaction between the bis-silylated reagent 7b and aldehydes (acetals), ketones (ketals) and ortholactones respectively. This simple methodology was applied to the rapid synthesis of a pheromone containing a [4,5]-spiroketal unit.

The Congress Center of the Santa Lucia Foundation Research Hospital in Rome, Italy, was the venue from September 2–5, 2009 of the First European Congress on Microbial Biofilms — EUROBIOFILMS 2009, providing the participants with a valuable forum for a fruitful scientific exchange in the field of microbial biofilms (Fig. 1). Figure 1 The 500-seat congress hall of the Santa Lucia Foundation during EUROBIOFILMS 2009. The original proposal to organize such a conference dates back to the Executive Board meeting of the newly established Study Group on Biofilms (ESGB) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), held in Copenhagen on April 2005. On that occasion, as Member-elect, Gianfranco Donelli highlighted the program of the First Workshop on Microbial Biofilms that he was organizing at the Italian National Institute of Health in Rome, June 2005, and proposed to hold a European congress on biofilms under the ESCMID umbrella in the future. During these years, in addition to the above-mentioned workshop (attended by 223 participants, mostly from Italy), three international conferences on biofilms, known as Biofilm I, II and III, were held in Germany (Osnabruck, 2004; Leipzig, 2006; Munich, 2008). However, each of these scientific events was attended mostly by participants from the organizing country. Thus, the idea to organize a large conference in Europe as a counterpart to the four Biofilm Conferences previously sponsored by the American Society for Microbiology represented a difficult, but exciting challenge. In fact, the recognition of a Congress as European should not be based only on its occurrence in a European country, but requires the involvement as much as possible of scientists from the different European countries, including the members of the Organizing and Scientific Committees as well as the invited speakers. Further, the most important European Organizations in the field of microbiology, …

Objectives: To investigate the in vitro antibacterial activity of silver-processed catheters for use in neurosurgery using clinically predictive tests. Methods: The antimicrobial activity of a commercially available silver-processed external ventricular drain catheter was evaluated against Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Propionibacterium acnes. Non-impregnated catheters were used as controls. Two assays were performed: (i) testing the ability of the catheter to kill 100% of the attached bacteria (tK100); and (ii) in vitro challenge to determine the ability to prevent colonization under flow conditions. High and low inocula (10 4 and 10 7 cfu/mL) were used. Silver-processed and control catheters were examined by scanning electron microscopy and focused ion beam scanning electron microscopy; electron back-scatter and energy-dispersive X-ray analyses were used to investigate the distribution of silver within the processed catheter. Results: The silver-processed catheters were not able to kill any of the bacteria tested in the tK100 assay at high inoculum. At low inoculum S. epidermidis was eradicated and some activity was seen against E. coli but without complete eradication. MRSA was also not eradicated even at low inoculum. The in vitro challenge test showed no prevention of colonization for any of the strains. Silver particles were shown to be >500 nm in size. Conclusions: The commercial silver-impregnated catheter was not able to eradicate MRSA or E. coli and while it showed activity against S. epidermidis in one assay it was unable to prevent colonization in vitro under in-flow conditions. This is consistent with clinical studies on silver-processed catheters.

SUMMARY Bacteriological studies were carried out in 100 operations for insertion or revision of cerebrospinal fluid shunts. Nine cases of colonisation occurred within two months of the operation and the causative organisms in seven of the nine cases were shown to have been present on the patient during surgery. It is suggested that iodine-based skin-cleansing agents are unsuitable for use in this type of operation, as in some cases skin organisms were shown to persist until the end of the operation. 58 per cent of wounds sampled before suture were found to contain these organisms, and it is suggested that they gain entry into the shunt from the wound edges and the subcutaneous tissues during manipulation and connection of the shunt components. There was a high incidence of post-operative bacteraemia, but this was not found to be associated with early shunt colonisation. RESUME Des etudes bacterioloyques ont ete entreprises au decours de cent interventions pour insertion ou conirole de shunt de lcr. Neuf cas de colonisation bacterienne se sont manifestes dans les deux mois de l'intervention et pour sept des neuf cas, on a pu demontrer la presence des organismes en cause chez le malade au cours de l'infection. II est suggere que les agents desinfectants cutanes e base d'iode ne sont pas utilisables pour ce type d'intervention comme le montre le fait que certains organismes cutanes peuvent survivre jusqu'a la fin de l'intervention. 58 pour cent des ouvertures cutanees controlees avant suture, contenaient de tels organismes et il est suggere qu'ils peuvent penetrer dans le shunt e partir des bords de l'incision et du tissu sous-cutane durant la manipulation et la fixation des constituants du shunt. II a ete note une frequence elevee de bacteriemie post-operatoire mais celle-ci ne parait pas associee e la colonisation precoce du shunt. ZUSAMMENFASSUNG Bei 100 Operationen zum Einlegen oder zur Revision von Liquorshunts wurden bakteriologische Untersuchungen durchgefuhrt. Innerhalb von zwei Monaten nach der Operation traten neun Falle von Keimbesiedlung auf, und in sieben der neun Falle konnte gezeigt werden, das die verursachenden Organismen schon wahrend der Operation beim Patienten vorhanden waren. Es wird vermutet, das die Hautdesinfizientien auf Jodbasis zur Verwendung bei diesen Operationen ungeeignet sind, da in einigen Fallen die Hautkeime bis zum Ende der Operation uberlebten. Man fand bei 58 Prozent der Wunden bei Untersuchung vor der Naht, das sie diese Organismen enthielten, und wahrscheinlich gelangen sie in das Shuntsystem von den Wundecken aus oder dem subkutanen Gewebe wahrend der Manipulationen oder des Kontaktes mit Shuntteilen. Das Auftreten von postoperativen Bakteriamien war hoch, stand aber in keinem Zusammenhang mit einer fruhen Besiedlung des Shunts. RESUMEN Se realizaron estudios bacterianos en cien operaciones hechas para insertar o revisar derivaciones de l.c.r. Nueve casos de colonizacion tuvieron lugar dentro de los dos meses despues de la operacion y los organismos causales en siete de los nueve casos, se demostro que estaban presentes en el paciente durante la intervencion. Se sugiere que los agentes limpiantes de la piel a base de yodina no son apropiados para este tipo de operaciones. Se hallo que el 58 por ciento de las heridas de las que se obtuvieron muestras antes de la sutura, contenian estos organismos, y se piensa que puedan introducirse en la derivacion a partir de los bordes de la herida y de los tejidos subcutaneos durante la manipulacion y conexion de los componentes de la derivacion. Hubo una alta incidencia de bacteriemia post-operatoria, pero no se hallo que estuviera asociada a la colonizacion precoz de la derivacion.

SUMMARY Staphylococci of subdivision siia can be shown to produce a large amount of mucoid substance during their growth, and it has been shown that they produce this substance in vivo when they colonise Holter shunts. It is suggested that this mucoid substance plays a part in maintaining colonisation by enabling microcolonies to adhere to the valve wall, and that it protects the organisms from the action of lysozyme and antibiotics. RESUME Production excessive de substance mucoide par le staphylocoque SIIA: facteur en cause dans la colonisation des shunts de Holter Les staphylocoques du sous-groupe sira produisent au cours de leur croissance, une quantite importante de substance mucoide et il a ete montre qu'ils peuvent agir ainsi in vivo quand ils colonisent un shunt de Holter. II est suggere que cette substance mucoide peut jouer un role dans le maintien de la colonisation en permettant a des colonies micro-biennes d'adherer aux parois de la valve et d'etre protegees de I'action des lysozymes et antibiotiques. ZUSAMMENFASSUNG Ubermaβige Produktion mukoider Substanzen beim Staphylokokkus SIIA: eiti Faktor, der moglicherweise bei der Besiedlung von Holter Shunts eine Rolle spielt Staphylokokken der Untergruppe srra konnen wahrend ihres Wachstums nachweislich grose Mengen mukoider Substanzen produzieren und es ist gezeigt worden, das sie diese Substanzen in vivo produzieren, wenn sie Holter Shunts besiedeln. Es wird diskutiert, das diese mukoide Substanz fur die dauerhafte Besiedlung eine Rolle spielt, in dem sie Mikrokolonien ermoglicht, an der Klappenwand zu haften und die Organismen vor der Wirkung von Lysozymen und Antibiotika schutzt. RESUMEN Excesiva produccion de sustancia mucoide en el estafilococo SIIA: un posible factor de colonizacion de las vavulas de Holter Puede demostrarse que los estafilococos de la subdivision siia producen una gran cantidad de sustancia mucoide durante su crecimiento y se ha demostrado que la producen in vivo cuando colonizan las desvaciones de Holter. Se sugiere que esta sustancia mucoide juega un papel en el mantenimiento de la colonizacion, facilitando a las microcolonias su adherencia a la pared valvular, y que protege a los germenes de la accion del lisozima y de los antibioticos.

A naturally-occurring, age-related rise in titre of antibody to Staph. albus in both hydrocephalic and non-hydrocephalic children is demonstrated in this report. In view of this finding, the value of serial determinations of antibody titre in children with shunts is discussed in terms of an organised surveillance programme.

This study of the effects of various factors on the antibacterial activity of gentamicin-impregnated Silastic has shown that it is unaffected by autoclaving and storage. It has also shown that this activity persists for long periods under crudely simulated in-use conditions. This form of Silastic will be studied further in an attempt to evaluate the kinetics of gentamicin diffusion within it, and to investigate its possible use in preventing colonisation of Holter shunts.

UMMARY A system of antibiotic prophylaxis has recently been described which is said to lower the incidence of wound infection in various surgical procedures, and which also evades the problem of increase in resistant bacteria. In the investigation reported here, this system was applied to the prevention of colonisation following shunt surgery and was found to have no beneficial effect. It is suggested that this finding may be peculiar to operations involving the implantation of hollow devices. RESUME Prophylaxie antibiotique dans les shunts ehirurgicaux Un systeme de prophylaxie antibiotique a ete recemment decrit pour abaisser la frequence de l'infection des plaies dans differents procedes ehirurgicaux et solutionnant le probleme des resistances bacteriennes croissantes. Dans la recherche effectuee par les auteurs, ce systeme a ete appliquea la prevention de la colonisation faisant suite a une chirurgie de shunts et s'est revele sans effet benefique. Il est suggere que cet echec peut etre specifique aux interventions utilisant l'implantation de materiel creux. ZUSAMMENFASSUNG Antibiotische Prophylaxe bei Ventiloperationen Kurzlich wurde ein Schema zur antibiotischen Prophylaxe beschrieben, das angeblich die Wundinfektionsrate bei unterschiedlichen chirurgischen Eingriffen senken sollte und das gleichzeitig das Problem der zunehmenden resistenten Bakterien ausweitet. Bei der Untersuchung, uber die hier berichtet wird, wurde dieses Schema angewandt, um die Keimbesiedelung nach Ventiloperation zu verhindern, es konnte jedoch kein therapeutisch gunstiger Effekt damit erzielt werden. Es ist anzunehmen, das dieser Befund fur alle Operationen zutrifft, die sich mit der Implantation von Hohlraumsystemen beschaftigen. RESUMEN Profilaxis antibiotica en la cirugia de la derivacion Recientemente se ha descrito un sistema de profilaxia antibiotica, que se dice que disminuye la incidencia de la infeccion de las heridas en diversas intervenciones quirurgicas. y que evita ademas el problema del aumento de resistencia de las bacterias. En la investigacion comunicada aqui, este sistema se aplico en la prevencion de la colonizacion post-quirurgica en las derivaciones y se vio que no tenia ningun efecto beneficioso. Se sugiere que este hallazgo puede ser especifico de las operaciones en que se implantan artificios huecos.

Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.

It is important to accept that, while shunt infection rates can be reduced by adherence to rigorous surgical protocols, prophylactic antibiotics have little impact and skin bacteria will continue to gain access to the shunt. The Bactiseal catheter is intended to reduce infection in hydrocephalus shunts and external ventricular drainage by preventing bacterial colonization of the catheters. This article outlines the causes of such infections and discusses a number of strategies for prevention. The principle of the Bactiseal system is presented, along with in-vitro evaluation. Finally, clinical studies of its effi cacy are discussed. While Bactiseal has limitations, clinical trials have shown signifi cant reductions in shunt infection rate. Fewer data on the use of Bactiseal external ventricular drainage catheters are available, and clinical trial results are awaited.

Catheters are used in neurosurgery mainly forcerebrospinal fluid (CSF) drainage, taking the formof either shunts or external ventricular drainage(EVD) devices. While approximately 4000 shuntsare inserted each year in the UK (UK ShuntRegistry, unpublished data), numbers are notavailable for EVDs but they are certainly higher.CSF shunts are used for permanent managementof intracranial pressure in hydrocephalus, whileEVDs are used for short-term (2 3 days to 2 3weeks) management of intracranial pressure dueto subarachnoid haemorrhage, trauma, tumoursor infection. In each case, infection is a seriouscomplication associated with poor outcome.Totallyinternal devices such as shunts are classified asCategory 1 devices, whereas EVDs are partiallyimplanted and are therefore Category 2 devices

Received 3 November 2006; returned 13 December 2006; revised 22 January 2007; accepted 23 January 2007 Objectives: Triclosan is in widespread use in domestic, commercial and healthcare settings and is used to reduce methicillin-resistant Staphylococcus aureus (MRSA) load in carriers. Triclosan resistance is uncommon, usually being due to mutation in fabI or overexpression of efflux pumps. This study investigated the ability of triclosan-containing silicone elastomer to kill MRSA adherent to its surface. Methods: Silicone discs containing triclosan were prepared by a matrix-expansion method previously described. Discs were exposed to three strains of MRSA for 1 h for adhesion to take place. After incubation, discs were removed at intervals, sonicated and the sonicates analysed by chemiluminescence and viable counting. Survivors were found to consist of small colony variants (SCVs). These were then subjected to tests for known SCV characteristics and for susceptibility to triclosan. Results: Viable counts fell until 51 h, when they began to increase, due to SCV. Of the three SCV strains, two showed impaired coagulase production and all showed reduced deoxyribonuclease production. None was auxotrophic. MICs of triclosan in the SCV rose by between 8- and 67-fold. Conclusions: Prolonged exposure of MRSA to triclosan-impregnated silicone, as in ‘antimicrobial’ plastics or catheters, resulted in the induction of SCV status and triclosan resistance. This has implications for industrial, medical and domestic use of polymers containing triclosan. SCVs are pathogenic and persistent. The widespread use of triclosan could lead to infection with MRSA SCVs, and new antimicrobials with physiological targets similar to that of triclosan might give rise to SCV resistance in clinical use.

Objectives: Infection remains a major complication of shunting for hydrocephalus. The causative bacteria, mainly staphylococci, gain access to the shunt at operation and colonize the shunt tubing. This leads to bio- film development requiring shunt removal. As there is no clear evidence to support antibiotic prophylaxis, we have developed an impregnated antimicrobial shunt material. This study aimed to elucidate its mode of action in terms of bacterial adherence and killing kinetics. Methods: Plain and impregnated material, with and without plasma protein conditioning film, were exposed to Staphylococcus epidermidis. Bacterial adherence was determined by scanning electron microscopy, chemiluminescence and culture. Time taken to kill 100% of bacteria (tK100) was determined by serial chemi- luminescence, culture and the use of differential viability microscopy. Results: The antimicrobial material did not reduce bacterial adherence. However, 100% of attached bacteria were killed in 48-52 h, even in the presence of a conditioning film. Conclusions: Impregnated antimicrobial material is likely to reduce shunt infection rates significantly with- out the risks and side effects of systemic antibiotics.

Recent attention has focused on the possibility that otitis media with effusion (OME) may represent a chronic infective state such as those evidenced in conditions secondary to biofilms or small colony variants. This review discusses the evidence suggesting that this may indeed be the case and explains why this may prove to be important in the future management of this condition by discussing recent advances in understanding these bacterial phenotypic variants.

Background Prostaglandin (PG) E2 (PGE2) appears to have a role in stimulating production of interleukin-6 (IL-6) and apoptosis of smooth muscle cells in diseased aortic tissue. These actions are mediated by cellular receptors for PGE2 EP receptors. Objective This study was undertaken to identify EP receptors associated with production of IL-6 by aortic explants. Methods Biopsy specimens of abdominal aortic aneurysm were used for explant culture and preparation of messenger RNA. The presence of EP1, EP2, EP3, and EP4 receptors in tissue and cells was investigated with reverse-transcriptase polymerase chain reaction. IL-6 and cyclic adenosine monophosphate were measured with an enzyme-linked immunosorbent assay. Results PGE2 or 11-deoxy-PGE1 (EP 2/3/4 agonist) reversed partially the indomethacin suppression of IL-6 secretion from explant cultures, whereas butaprost (EP2 receptor agonist) and sulprostone (EP 1/3 receptor agonist) had no effect. Aortic biopsy specimens expressed EP2, EP3-III, and EP4 receptors. Aortic smooth muscle cells expressed EP2 receptor and four variants of EP3 receptor, ie, EP3-Ib, EP3-II, EP3-III, and EP3-IV, but PGE2 did not stimulate secretion of IL-6. In contrast, PGE2 or 11-deoxy-PGE1 stimulated secretion of IL-6 from aortic macrophages. Conclusions In aortic explants, PGE2 stimulates IL-6 secretion by activation of EP4 receptors, present in macrophages.

Summary Background Bacterial colonisation of indwelling medical devices by coagulase-negative staphylococci is a prevalent risk in intensive-care units. Factors determining biofilm formation and progression to catheter-related infection are incompletely understood. We postulated that administration of inotropic agents via indwelling intravenous catheters may stimulate growth and formation of biofilms by Staphylococcus epidermidis . Methods Inocula representing physiologically relevant infecting doses of S epidermidis were incubated in a minimum medium supplemented with fresh human plasma in the presence or absence of pharmacological concentrations of norepinephrine or dobutamine. Biofilm formation on polystyrene and medical-grade silicone was examined. After incubation, cultures were assessed for growth and formation of biofilms by colony counting and scanning electronmicroscopy. The production of exopolysaccharide, a major constituent of S epidermidis biofilms, was also assessed by use of immunofluorescence microscopy. Findings Incubation of S epidermidis with catecholamine inotropes in the presence of human plasma resulted in a significant increase in growth compared with control on both polystyrene and silicone surfaces, with pronounced increases in biofilm formation as visualised by scanning electronmicroscopy. Experiments with transferrin labelled with radioactive iron showed the ability of catecholamine inotropes to facilitate acquisition of iron by S epidermidis . Immunofluorescence microscopy revealed extensive exopolysaccharide production associated with S epidermidis biofilms. Interpretation The ability of catecholamine inotropic drugs to stimulate bacterial proliferation and biofilm formation may be an aetiological factor in the development of intravascular catheter colonisation and catheter-related infection. The removal of iron from transferrin for subsequent use by S epidermidis is a possible mechanism by which catecholamine inotropes stimulate bacterial growth as biofilms.

A case is reported of a pregnant 16-year-old-woman diagnosed with Acute promyelocytic leukaemia (APL) at 25 weeks gestation and treated with all-trans retinoic acid (ATRA) (45 mg/m2) for 25 days in combination with chemotherapy. She achieved a complete cytogenetic and molecular remission. Clinical course was complicated, with an intracerebral bleed, respiratory failure requiring ventilation and prolonged pancytopenia following initial chemotherapy. A live female infant was born at 28 weeks gestation who survived to discharge with significant pulmonary complications. She remains oxygen dependent at 6 months of age. ATRA has been used from the 3rd week of gestation, but fetal malformations are common during the first trimester. In contrast it seems to be safe in the second and third trimesters with regard to teratogenesis but can cause other side-effects. Most successful outcomes in treatment of APL during pregnancy are seen after treatment with ATRA and delivery of the baby at as late a stage as possible. Pregnancies terminated before remission has been obtained or those treated in the first trimester have a poor maternal outcome.