Intrathecal daptomycin use in a challenging case of Enterococcus faecium ventriculitis.

Treatment of ventriculitis caused by enterococci can be challenging, and antibiotic options are limited. We describe a case of device-related ventriculitis caused by vancomycin-resistant Enterococcus faecium , refractory to initial antibiotics. Our management approach included intrathecal daptomycin. There were no attributable adverse events, and the patient remained infection-free following ventriculo-peritoneal shunt insertion and cessation of antibiotics.

'It makes life so much easier'-experiences of users of the MicroGuide™ smartphone app for improving antibiotic prescribing behaviour in UK hospitals: an interview study.

OBJECTIVES: To understand the impact on prescribing behaviour of an antimicrobial therapy guidelines smartphone app, in widespread use in hospitals in the UK. METHODS: Twenty-eight doctors and five nurse prescribers from four purposively selected hospitals in the UK participated in behavioural theory-informed semi-structured interviews about their experiences of using the MicroGuide™ smartphone app. Data were analysed using a thematic content analysis. RESULTS: Five themes emerged from the interview data: convenience and accessibility; validation of prescribing decisions; trust in app content; promotion of antimicrobial stewardship; and limitations and concerns. Participants appreciated the perceived convenience, accessibility and timesaving attributes of the app, potentially contributing to more prompt treatment of patients with time-critical illness. The interviewees also reported finding it reassuring to use the app to support decision-making and to validate existing knowledge. They trusted the app content authored by local experts and considered it to be evidence-based and up-to-date. This was believed to result in fewer telephone calls to the microbiology department for advice. Participants recognized the value of the app for supporting the goals of antimicrobial stewardship by promoting the responsible and proportionate use of antimicrobials. Finally, a number of limitations of the app were reported, including the risk of de-skilling trainees, cultural problems with using smartphones in clinical environments and software technical problems. CONCLUSIONS: The MicroGuide app was valued as a means of addressing an unmet need for updated, concise, trustworthy specialist information in an accessible format at the bedside to support safe and effective antimicrobial prescribing.

Multicentre study of the in vitro activity of ceftolozane/tazobactam and other commonly used antibiotics against Pseudomonas aeruginosa isolates from patients in the UK.

OBJECTIVES: To evaluate the in vitro activity of ceftolozane/tazobactam and other commonly used antipseudomonal antibiotics against geographically spread Pseudomonas aeruginosa isolates in the UK using disc susceptibility testing. METHODS: The in vitro activity of ceftolozane/tazobactam and nine other commonly used antipseudomonal antibiotics was evaluated. Isolates were collected between January 2015 and April 2018. Susceptibility results were interpreted using EUCAST 2018 criteria. RESULTS: Overall, 1326 clinical isolates from 14 centres in the UK were tested. The majority of the isolates were collected from non-cystic fibrosis (non-CF) patients (n = 1123, 85.0%). In addition, 199 cystic fibrosis (CF) isolates were collected from 10 centres. Overall susceptibility to ceftolozane/tazobactam was 89.3% (n = 1181), which included 128 CF and 1053 non-CF isolates. The other antibacterial agents with the highest susceptibility were tobramycin (92.4%, n = 1221) and piperacillin/tazobactam (90.7%, n = 1199). Susceptibility to all antibacterial agents was lower for CF isolates. Piperacillin/tazobactam was the most active of the antibacterial agents tested, followed by ceftolozane/tazobactam (70.4% and 64.3%, respectively), and <60% of CF isolates were susceptible to ceftazidime and the carbapenems. The reason for the higher rates of susceptibility to piperacillin/tazobactam and lower susceptibility to ceftazidime compared with other studies is unclear. CONCLUSIONS: The data presented here support the need to investigate the place of ceftolozane/tazobactam as a treatment option in the management of pseudomonal infections, particularly in patients with CF. The results highlight the importance of routine testing of new antibacterial agents and of making the data available to clinicians to make appropriate and informed treatment choices.

The heterogeneous causal effects of neonatal care: a model of endogenous demand for multiple treatment options based on geographical access to care.

Neonatal units in the UK are organised into three levels, from highest Neonatal Intensive Care Unit (NICU), to Local Neonatal Unit (LNU) to lowest Special Care Unit (SCU). We model the endogenous treatment selection of neonatal care unit of birth to estimate the average and marginal treatment effects of different neonatal designations on infant mortality, length of stay and hospital costs. We use prognostic factors, survival and hospital care use data on all preterm births in England for 2014-2015, supplemented by national reimbursement tariffs and instrumental variables of travel time from a geographic information system. The data were consistent with a model of demand for preterm birth care driven by physical access. In-hospital mortality of infants born before 32 weeks was 8.5% overall, and 1.2 (95% CI: -0.7, 3.2) percentage points lower for live births in hospitals with NICU or SCU compared to those with an LNU according to instrumental variable estimates. We find imprecise differences in average total hospital costs by unit designation, with positive unobserved selection of those with higher unexplained absolute and incremental costs into NICU. Our results suggest a limited scope for improvement in infant mortality by increasing in-utero transfers based on unit designation alone.

Estimating the effectiveness and cost-effectiveness of establishing additional endovascular Thrombectomy stroke Centres in England: a discrete event simulation.

BACKGROUND: We have previously modelled that the optimal number of comprehensive stroke centres (CSC) providing endovascular thrombectomy (EVT) in England would be 30 (net 6 new centres). We now estimate the relative effectiveness and cost-effectiveness of increasing the number of centres from 24 to 30. METHODS: We constructed a discrete event simulation (DES) to estimate the effectiveness and lifetime cost-effectiveness (from a payer perspective) using 1 year's incidence of stroke in England. 2000 iterations of the simulation were performed comparing baseline 24 centres to 30. RESULTS: Of 80,800 patients admitted to hospital with acute stroke/year, 21,740 would be affected by the service reconfiguration. The median time to treatment for eligible early presenters (< 270 min since onset) would reduce from 195 (IQR 155-249) to 165 (IQR 105-224) minutes. Our model predicts reconfiguration would mean an additional 33 independent patients (modified Rankin scale [mRS] 0-1) and 30 fewer dependent/dead patients (mRS 3-6) per year. The net addition of 6 centres generates 190 QALYs (95%CI - 6 to 399) and results in net savings to the healthcare system of £1,864,000/year (95% CI -1,204,000 to £5,017,000). The estimated budget impact was a saving of £980,000 in year 1 and £7.07 million in years 2 to 5. CONCLUSION: Changes in acute stroke service configuration will produce clinical and cost benefits when the time taken for patients to receive treatment is reduced. Benefits are highly likely to be cost saving over 5 years before any capital investment above £8 million is required.

Opportunities for antimicrobial stewardship in patients with acute bacterial skin and skin structure infections who are unsuitable for beta-lactam antibiotics: a multicenter prospective observational study.

PURPOSE: The objective of this prospective, observational study was to describe the treatment, severity assessment and healthcare resources required for management of patients with acute bacterial skin and skin structure infections who were unsuitable for beta-lactam antibiotic treatments. METHODS: Patients were enrolled across five secondary care National Health Service hospitals. Eligible patients had a diagnosis of acute bacterial skin and skin structure infection and were considered unsuitable for beta-lactam antibiotics (e.g. confirmed/suspected methicillin-resistant Staphylococcus aureus, beta-lactam allergy). Data regarding diagnosis, severity of the infection, antibiotic treatment and patient management were collected. RESULTS: 145 patients with acute bacterial skin and skin structure infection were included; 79% (n = 115) patients received greater than two antibiotic regimens; median length of the first antibiotic regimen was 2 days (interquartile range of 1-5); median time to switch from intravenous to oral antibiotics was 4 days (interquartile range of 3-8, n = 72/107); 25% (n = 10/40) patients with Eron class 1 infection had systemic inflammatory response syndrome, suggesting they were misclassified. A higher proportion of patients with systemic inflammatory response syndrome received treatment in an inpatient setting, and their length of stay was prolonged in comparison with patients without systemic inflammatory response syndrome. CONCLUSION: There exists an urgent need for more focused antimicrobial stewardship strategies and tools for standardised clinical assessment of acute bacterial skin and skin structure infection severity in patients who are unsuitable for beta-lactam antibiotics. This will lead to optimised antimicrobial treatment strategies and ensure effective healthcare resource utilisation.

Comparative healthcare-associated costs of methicillin-resistant Staphylococcus aureus bacteraemia-infective endocarditis treated with either daptomycin or vancomycin.

Complex infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with high healthcare and societal costs; thus, evaluation of the costs and health benefits of interventions is an important consideration in a modern healthcare system. This study estimated the cost consequences of the use of daptomycin compared with vancomycin for the first-line treatment of patients with proven MRSA-induced bacteraemia-infective endocarditis (SAB-IE) with a vancomycin minimum inhibitory concentration (MIC) >1mg/L in the UK. A decision model was developed to assess total healthcare costs of treatment, including inpatient, outpatient and drug costs. Data were sourced from the literature (treatment efficacy and safety), a physician survey (resource use) and publicly available databases (unit costs). Assuming the same length of stay for daptomycin and vancomycin, the total healthcare costs per patient were £17917 for daptomycin and £17165 for vancomycin. However, extrapolating from published studies and supported by a physician survey, daptomycin was found to require fewer therapeutic switches and a shorter length of stay. When the length of stay was reduced from 42 days to 28 days, daptomycin saved £4037 per person compared with vancomycin. In conclusion, daptomycin is an effective and efficient alternative antibiotic for the treatment of SAB-IE. However, the level of cost saving depends on the extent to which local clinical practice allows early discharge of patients before the end of their antibiotic course when responding to treatment.

Recognizing Success in the Chaplain Profession: Connecting Perceptions With Practice.

The current investigation examines the communicative hallmarks of successful chaplaincy work as articulated by professional chaplains providing spiritual care at the end-of-life. Data grounded in qualitative interviews with 32 chaplains of various denominations and lengths of service reveals a challenge in gauging success when working with dying patients and families. Chaplains reported nonverbal hallmarks of success consist of (a) intrapersonal sense of accomplishment, (b) progress in fulfilling patient needs, and (c) meaningful connection with patients. Verbal hallmarks of success include (a) patient affirmation, (b) family affirmation, and the (c) chaplain being asked to participate in religious rites. In practice, the authors conjecture, chaplains assess professional competency in the self, patient, and family domains. Implications and future directions are discussed.

National characteristics and variation in Arabic handwriting.

From each of four Arabic countries; Morocco, Tunisia, Jordan and Oman, 150 participants produced handwriting samples which were examined to assess whether national characteristics were discernible. Ten characters, which have different configurations depending upon their position in the word, along with one short word, were classified into distinguishable forms, and these forms recorded for each handwriting sample. Tests of independence showed that character forms used were not independent of country (p<0.001) for all but one character-position (this was dropped from subsequent analyses). A correspondence analysis ordination plot and analysis of similarity (R=0.326, p=0.0002) showed that whole samples were discernibly grouped by country, and a tree analysis produced a classification which was 71% accurate for the original data and 83% accurate for 80 new handwriting samples that underwent 'blind' classification. When the countries were combined into two regions, North Africa and Middle East, the grouping was more marked. Thus, there appears to be some scope for narrowing down the nationality, and particularly the wider geographical region of an author based upon the character forms they use in Arabic handwriting.

Talking about end-of-life preferences in marriage: applying the theory of motivated information management.

The theory of motivated information management (TMIM) provides one framework to examine information-seeking behaviors, especially in conversations involving sensitive or difficult information such as preferences for end-of-life (EOL) care. The spouse plays a significant role in decision making surrounding EOL care. Consequently, individuals need information about spouses' EOL preferences in order to ensure carrying out those desires. Our findings support the value of TMIM as a framework to understand factors that influence couples' EOL care information-seeking behaviors. In support of the theory, we provide factors that influence the initiation or avoidance of EOL conversations between spouses.

Translating spiritual care in the chaplain profession.

Chaplains provide a much-needed service to patients and families requiring spiritual care in the healthcare setting. Despite evidence documenting improvements quality of life for patients using spiritual services, chaplains experience challenges in translating the benefits they provide into concepts understood by patients, team members, and administrators. A qualitative study using interviews with 19 chaplains found that translation problems occur in three main areas: (a) justifying the role to patients and families, (b) determinations of what constitutes a "productive" employee, and (c) effective collaboration with other members of the health care team. This study outlines several strategies used by chaplains to ease the process of translation, as well as some directions for future research.

Using daptomycin in hospitalised patients with cSSTI caused by Staphylococcus aureus has an impact on costs.

BACKGROUND: The aim was to assess the cost impact of daptomycin compared to vancomycin treatment in patients hospitalised for complicated skin and soft-tissue infection (cSSTI) with suspected methicillin-resistant Staphylococcus aureus infection in the UK. METHODS: A decision model was developed to estimate the costs associated with cSSTI treatment. Data on efficacy, treatment duration and early discharge from published clinical trials were used, with data gaps on standard clinical practice being filled by means of clinician interviews. RESULTS: Total health-care costs per patient were GBP 6,214 and GBP 6,491 for daptomycin and vancomycin, respectively. A sensitivity analysis suggested that modifying the parameters within a reasonable range does not impact on the conclusion that the higher cost of daptomycin is likely to be offset by lower costs of monitoring and hospitalisation. CONCLUSIONS: This study demonstrates that daptomycin not only provides an alternative treatment for multiple resistant infections, but may also reduce National Health Service costs.

4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.

The effect of material choice on biofilm formation in a model warm water distribution system.

Water distribution systems (WDS) are composed of a variety of materials and may harbour potential pathogens within surface-attached microbial biofilms. Biofilm formation on four plumbing materials, viz. copper, stainless steel 316 (SS316), ethylene propylene diene monomer (EPDM) and cross-linked polyethylene (PEX), was investigated using scanning electron microscope (SEM)/confocal microscopy, ATP-/culture-based analysis, and molecular analysis. Material 'inserts' were incorporated into a mains water fed, model WDS. All materials supported biofilm growth to various degrees. After 84 days, copper and SS316 showed no significant overall differences in terms of the level of biofilm formation observed, whilst PEX supported a significantly higher level of biofilm. EPDM exhibited gross contamination by a complex, multispecies biofilm, at a level significantly higher than was observed on the other materials, regardless of the analytical method used. PCR-DGGE analysis showed clear differences in the composition of the biofilm community on all materials after 84 days. The primary conclusion of this study has been to identify EPDM as a potentially unsuitable material for use as a major component in WDS.

Permanent draft genome sequence of Vibrio tubiashii strain NCIMB 1337 (ATCC19106).

Vibrio tubiashii NCIMB 1337 is a major and increasingly prevalent pathogen of bivalve mollusks, and shares a close phylogenetic relationship with both V. orientalis and V. coralliilyticus. It is a Gram-negative, curved rod-shaped bacterium, originally isolated from a moribund juvenile oyster, and is both oxidase and catalase positive. It is capable of growth under both aerobic and anaerobic conditions. Here we describe the features of this organism, together with the draft genome and annotation. The genome is 5,353,266 bp long, consisting of two chromosomes, and contains 4,864 protein-coding and 86 RNA genes.

Recommendations on: internal standard criteria, stability, incurred sample reanalysis and recent 483s by the Global CRO Council for Bioanalysis.

"The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry"

Identification of the class characteristics in the handwriting of Polish people writing in English.

An investigation was carried out to identify the class characteristics of Polish people writing in English and to specifically identify those characteristics that separate Polish handwriting from English handwriting. In the first stage, 40 Polish and 40 English handwriting samples were collected and systematically examined. In total, 31 features were identified that occurred in ≥25% of the Polish handwriting samples and therefore considered class characteristics. Of these, chi-square analyses identified 21 class characteristics that occurred significantly more in Polish compared to English handwriting. Twenty-one of the class characteristics in the Polish handwriting had similar constructions to the copybook pattern thus supporting the theory that class characteristics frequently stem from the taught writing system. In the second stage, an algorithm was developed using seventeen of the class characteristics that successfully discriminated between a further 13 Polish and 12 English handwriting samples.

An evidence base for patient-centered cancer care: a meta-analysis of studies of observed communication between cancer specialists and their patients.

OBJECTIVE: In the context of patients visiting cancer specialists, the objective is to test the association between both patient-centered communication (including Affective Behavior and Participation Behavior) and Instrumental Behavior and patients' post-visit satisfaction with a variety of visit phenomena. METHODS: Meta-analysis of 25 articles representing 10 distinct data sets. RESULTS: Both patient-centered- and instrumental behavior are significantly, positively associated with satisfaction, with patient-centered communication having a relatively stronger association. CONCLUSION: There is an evidence base for the efficacy of patient-centered care. PRACTICE IMPLICATIONS: Cancer specialists need to train to improve their patient-centered communication.

Biomechanical consequences of total plantar fasciotomy: a review of the literature.

BACKGROUND: Plantar fascia release for chronic plantar fasciitis has provided excellent pain relief and rapid return to activities with few reported complications. Cadaveric studies have led to the identification of some potential postoperative problems, most commonly weakness of the medial longitudinal arch and pain in the lateral midfoot. METHODS: An electronic search was conducted of the MEDLINE, ScienceDirect, SportDiscus, EMBASE, CINAHL, Cochrane, and AMED databases. The keywords used to search these databases were plantar fasciotomy and medial longitudinal arch. Articles published between 1976 and 2008 were identified. RESULTS: Collectively, results of cadaveric studies suggested that plantar fasciotomy leads to loss of integrity of the medial longitudinal arch and that total plantar fasciotomy is more detrimental to foot structure than is partial fasciotomy. In vivo studies, although limited in number, concluded that although clinical outcomes were satisfactory, medial longitudinal arch height decreased and the center of pressure of the weightbearing foot was excessively medially deviated postoperatively. CONCLUSIONS: Plantar fasciotomy, in particular total plantar fasciotomy, may lead to loss of stability of the medial longitudinal arch and abnormalities in gait, in particular an excessively pronated foot. Further in vivo studies on the long-term biomechanical effects of plantar fasciotomy are required.

Chronic exertional compartment syndrome of the foot.

Chronic exertional compartment syndrome (CECS) usually refers to myoneural ischemia from a reversible increase in tissue pressure within a myofascial compartment. CECS of the leg is well documented, as its first description by Mavor in 1956. CECS of the foot remains underdiagnosed, and has been reported in the literature only on an anecdotal basis. Wood Jones proposed that there were 4 compartments in the foot, but Manoli and Weber suggest that there are 9 separate compartments. Clinical signs and symptoms of CECS of the foot remain vague, diverse, and lack the consistency of its counterpart in the leg. The most effective treatment is a fasciotomy. We present a literature review of the condition to increase the awareness and high index of suspicion among the clinicians as the symptoms are often vague and, to consider the condition as part of the differential diagnosis.