Bloodstream Infection Due to Piperacillin/Tazobactam Non-Susceptible, Cephalosporin Susceptible Escherichia Coli: A Missed Opportunity for DE-Escalation of Therapy

An increasing number of reports describing Escherichia coli isolates with piperacillin/tazobactam resistance, despite retained cephalosporin susceptibility, suggest further emergence of this phenotypic resistance pattern. In this report, a patient with metastatic breast cancer presented to medical care after two days of chills, nausea, vomiting, reduced oral intake, and generalized weakness. Blood and urine cultures grew E. coli as identified by rapid diagnostics multiplex PCR and MALDI-TOF, respectively. The patient continued to manifest signs of sepsis with hypotension and tachypnea during the first three days of hospitalization despite empirical antimicrobial therapy with intravenous piperacillin/tazobactam. After in vitro antimicrobial susceptibility testing demonstrated a piperacillin/tazobactam minimal inhibitory concentration (MIC) of 64 and a ceftriaxone MIC of ≤1 mcg/mL, antimicrobial therapy was switched from intravenous piperacillin/tazobactam to ceftriaxone. All symptoms and signs of infection resolved within 48 h of starting ceftriaxone therapy. This report describes the clinical failure of piperacillin/tazobactam in the treatment of a bloodstream infection due to E. coli harboring a phenotypic resistance pattern of isolated piperacillin/tazobactam non-susceptibility. The case demonstrates the role of cephalosporins as potential treatment options and highlights the value of early de-escalation of antimicrobial therapy based on rapid diagnostic testing for microbial identification

Local status and power in area-based health improvement partnerships

This is the authors' PDF version of an article published in Health© 2014. The definitive version is available at http://hea.sagepub.comArea-based initiatives (ABIs) have formed an important part of public policy towards more socio-economically deprived areas in many countries. Co-ordinating service provision within and across sectors has been a common feature of these initiatives. Despite sustained policy interest in ABIs, little empirical work has explored relations between ABI providers and partnership development within this context remains under-theorised. This paper addresses both of these gaps by exploring partnerships as a social and developmental process, drawing on concepts from figurational sociology to explain how provider relations develop within an ABI. Qualitative methods were used to explore, prospectively, the development of an ABI targeted at a town in the north west of England. A central finding was that, although effective delivery of ABIs is premised on a high level of coordination between service providers, the pattern of interdependencies between providers limits the frequency and effectiveness of cooperation. In particular, the interdependency of ABI providers with others in their organisation (what is termed here ‘organisational pull’) constrained the ways in which they worked with providers outside of their own organisations. ‘Local’ status, which could be earned over time, enabled some providers to exert greater control over the way in which provider relations developed during the course of the initiative. These findings demonstrate how historically constituted social networks, within which all providers are embedded, shape partnership development. The theoretical insight developed here suggests a need for more realistic expectations among policy makers about how and to what extent provider partnerships can be managed. Keywords: partnership, collaboration, community services, area-based initiatives, organisational pull, figurational sociologyNational Health Service (NHS

CRAFT (Cerclage after full dilatation caesarean section): protocol of a mixed methods study investigating the role of previous in-labour caesarean section in preterm birth risk

BACKGROUND: Full dilatation caesarean sections are associated with recurrent early spontaneous preterm birth and late miscarriage. The risk following first stage caesarean sections, are less well defined, but appears to be increased in late-first stage of labour. The mechanism for this increased risk of late miscarriage and early spontaneous preterm birth in these women is unknown and there are uncertainties with regards to clinical management. Current predictive models of preterm birth (based on transvaginal ultrasound and quantitative fetal fibronectin) have not been validated in these women and it is unknown whether the threshold to define a short cervix (≤25 mm) is reliable in predicting the risk of preterm birth. In addition the efficacy of standard treatments or whether benefit may be derived from prophylactic interventions such as a cervical cerclage is unknown. METHODS: There are three distinct components to the CRAFT project (CRAFT-OBS, CRAFT-RCT and CRAFT-IMG). CRAFT-OBS: Observational Study; To evaluate subsequent pregnancy risk of preterm birth in women with a prior caesarean section in established labour. This prospective study of cervical length and quantitative fetal fibronectin data will establish a predictive model of preterm birth. CRAFT-RCT: Randomised controlled trial arm; To assess treatment for short cervix in women at high risk of preterm birth following a fully dilated caesarean section. CRAFT-IMG: Imaging sub-study; To evaluate the use of MRI and transvaginal ultrasound imaging of micro and macrostructural cervical features which may predispose to preterm birth in women with a previous fully dilated caesarean section, such as scar position and niche. DISCUSSION: The CRAFT project will quantify the risk of preterm birth or late miscarriage in women with previous in-labour caesarean section, define the best management and shed light on pathological mechanisms so as to improve the care we offer to women and their babies. TRIAL REGISTRATION: CRAFT was prospectively registered on 25th November 2019 with the ISRCTN registry ( https://doi.org/10.1186/ISRCTN15068651 )

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

The relevance of coagulation factor X protection of adenoviruses in human sera

Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5–FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad–FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP)

BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. DISCUSSION: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT0105027

Impacts of the COVID-19 pandemic and self-isolation on students and staff in higher education: A qualitative study

This qualitative study explored the impact of COVID-19 self-isolation and social restriction measures on university students, through the perspectives of both students and the staff supporting them. The study comprised 11 focus groups (students) and 26 individual interviews (staff) at a higher education institution in England during a period of national lockdown (January–March 2021). Participants were university students (n = 52) with self-isolation experiences and university staff (n = 26) with student-facing support roles. Focus group and interview data were combined and analysed using an inductive thematic approach. Four themes emerged: ‘Adaptation during the pandemic’, ‘Practical, environmental, and emotional challenges of self-isolating’, ‘Social factors and their impact on COVID-19 testing and self-isolation adherence’, and ‘Supporting self-isolation’. Students and staff struggled with the imposed restrictions and shift to online education. Students found it difficult to adapt to new expectations for university life and reported missing out on professional and social experiences. Students and staff noted concerns about the impact of online teaching on educational outcomes. Students endorsed varied emotional responses to self-isolation; some felt unaffected whilst others experienced lowered mood and loneliness. Students were motivated by pro-social attitudes; campaigns targeting these factors may encourage continued engagement in protective behaviours. Staff struggled to manage their increased workloads delivering support for self-isolating students. Universities must consider the support needs of students during self-isolation and prepare for the long-term impacts of the pandemic on student wellbeing and educational attainment. Greater support should be provided for staff during transitional periods, with ongoing monitoring of workforce stress levels warranted

Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cells

<p>Abstract</p> <p>Background</p> <p>Viruses bind to specific cellular receptors in order to infect their hosts. The specific receptors a virus uses are important factors in determining host range, cellular tropism, and pathogenesis. For adenovirus, the existing model of entry requires two receptor interactions. First, the viral fiber protein binds Coxsackie and Adenovirus Receptor (CAR), its primary cellular receptor, which docks the virus to the cell surface. Next, viral penton base engages cellular integrins, coreceptors thought to be required exclusively for internalization and not contributing to binding. However, a number of studies reporting data which conflicts with this simple model have been published. These observations have led us to question the proposed two-step model for adenovirus infection.</p> <p>Results</p> <p>In this study we report that cells which express little to no CAR can be efficiently transduced by adenovirus. Using competition experiments between whole virus and soluble viral fiber protein or integrin blocking peptides, we show virus binding is not dependent on fiber binding to cells but rather on penton base binding cellular integrins. Further, we find that binding to low CAR expressing cells is inhibited specifically by a blocking antibody to integrin αvβ5, demonstrating that in these cells integrin αvβ5 and not CAR is required for adenovirus attachment. The binding mediated by integrin αvβ5 is extremely high affinity, in the picomolar range.</p> <p>Conclusions</p> <p>Our data further challenges the model of adenovirus infection in which binding to primary receptor CAR is required in order for subsequent interactions between adenovirus and integrins to initiate viral entry. In low CAR cells, binding occurs through integrin αvβ5, a receptor previously thought to be used exclusively in internalization. We show for the first time that integrin αvβ5 can be used as an alternate binding receptor.</p

Does interhospital transfer improve outcome of acute myocardial infarction? A propensity score analysis from the Cardiovascular Cooperative Project

<p>Abstract</p> <p>Background</p> <p>Many patients suffering acute myocardial infarction (AMI) are transferred from one hospital to another during their hospitalization. There is little information about the outcomes related to interhospital transfer. The purpose of this study was to compare processes and outcomes of AMI care among patients undergoing interhospital transfer with special attention to the impact on mortality in rural hospitals.</p> <p>Methods</p> <p>National sample of Medicare patients in the Cooperative Cardiovascular Study (n = 184,295). Retrospective structured medical record review of AMI hospitalizations. Descriptive study using a retrospective propensity score analysis of clinical and administrative data for 184,295 Medicare patients admitted with clinically confirmed AMI to 4,765 hospitals between February 1994 and July 1995. Main outcome measure included: 30-day mortality, administration of aspirin, beta-blockers, ACE-inhibitors, and thrombolytic therapy.</p> <p>Results</p> <p>Overall, 51,530 (28%) patients underwent interhospital transfer. Transferred patients were significantly younger, less critically ill, and had lower comorbidity than non-transferred patients. After propensity-matching, patients who underwent interhospital transfer had better quality of care anlower mortality than non-transferred patients. Patients cared for in a rural hospital had similar mortality as patients cared for in an urban hospital.</p> <p>Conclusion</p> <p>Transferred patients were vastly different than non-transferred patients. However, even after a rigorous propensity-score analysis, transferred patients had lower mortality than non-transferred patients. Mortality was similar in rural and urban hospitals. Identifying patients who derive the greatest benefit from transfer may help physicians faced with the complex decision of whether to transfer a patient suffering an acute MI.</p