Middle manager responses to hospital co-workers' unprofessional behaviours within the context of a professional accountability culture change program: a qualitative analysis.

BACKGROUND: The critical role that middle managers play in enacting organisational culture change designed to address unprofessional co-worker behaviours has gone largely unexplored. We aimed to explore middle managers' perspectives on i) whether they speak up when they or their team members experience unprofessional behaviours (UBs); ii) how concerns are handled; iii) the outcomes; and iv) the role of a professional accountability culture change program (known as Ethos) in driving change. METHODS: Qualitative, constructivist approach. Five metropolitan hospitals in Australia which had implemented Ethos. Purposive sampling was used to invite middle-level managers from medicine, nursing, and non-clinical support services. Semi-structured interviews conducted remotely. Inductive, reflexive thematic and descriptive thematic analyses undertaken using NVivo. RESULTS: Thirty interviews (approximately 60 min; August 2020 to May 2021): Nursing (n = 12), Support Services (n = 10), and Medical (n = 8) staff, working in public (n = 18) and private (n = 12) hospitals. One-third (n = 10) had a formal role in Ethos. All middle managers (hearers) had experienced the raising of UBs by their team (speakers). Themes representing reasons for ongoing UBs were: staying silent but active; history and hierarchy; and double-edged swords. The Ethos program was valued as a confidential, informal, non-punitive system but required improvements in profile and effectiveness. Participants described four response stages: i) determining if reports were genuine; ii) taking action depending on the speaker's preference, behaviour factors (type, frequency, impact), if the person was known/unknown; iii) exploring for additional information; and iv) addressing either indirectly (e.g., change rosters) or directly (e.g., become a speaker). CONCLUSIONS: Addressing UBs requires an organisational-level approach beyond supporting staff to speak up, to include those hearing and addressing UBs. We propose a new hearer's model that details middle managers' processes after a concern is raised, identifying where action can be taken to minimise avoidant behaviours to improve hospital culture, staff and patient safety.

Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.

Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia.

Response to Therapy, Treatment Intolerance and Tyrosine Kinase Inhibitor Cessation Eligibility in a Real-World Cohort of Chronic Myeloid Leukaemia Patients.

Tyrosine kinase inhibitor (TKI) therapy has revolutionised chronic myeloid leukaemia (CML) management, it is however associated with significant side effects and economic burden. Recent studies have demonstrated that treatment free remission is possible in certain patients. The aim of this study was to characterise a real-world population in terms of response to therapy, treatment intolerance and potential eligibility for stopping treatment. Included were 105 CML patients diagnosed in Northern Ireland from March 2009-February 2018. Response to treatment was defined as per the 2009 and 2013 European Leukaemia Net guidelines. Potential for treatment cessation was assessed as per the 2017 UK Interim Expert Opinion on Discontinuing Tyrosine Kinase Inhibitor Treatment in Clinical Practice for Treatment-Free Remission in Chronic Myeloid Leukaemia. Our cytogenetic data cohort had a 12-month complete cytogenetic response rate of 66% and the molecular data cohort had a 12-month major molecular response rate of 38%. Of those commenced on 2nd line TKI therapy 81% achieved an optimal response at 12 months. Twenty-two patients developed intolerance and required a change in TKI therapy. The commonest side effects were gastro-intestinal upset (18%), transaminitis (16%) and fluid retention (16%). In our cohort, 20% were considered eligible to stop TKI therapy. The commonest reason for ineligibility was insufficient duration of therapy (25%). We observed that 1st and 2nd line TKI therapy are effective but problems with failure and intolerance persist. Additionally, this study identifies a cohort of patients who may attempt TKI cessation using the UK Interim Expert Opinion report on TKI therapy discontinuation.

The use of high-throughput sequencing to investigate an outbreak of glycopeptide-resistant Enterococcus faecium with a novel quinupristin-dalfopristin resistance mechanism.

High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.

Perinatal nutrition interacts with genetic background to alter behavior in a parent-of-origin-dependent manner in adult Collaborative Cross mice.

Previous studies in animal models and humans have shown that exposure to nutritional deficiencies in the perinatal period increases the risk of psychiatric disease. Less well understood is how such effects are modulated by the combination of genetic background and parent-of-origin (PO). To explore this, we exposed female mice from 20 Collaborative Cross (CC) strains to protein deficient, vitamin D deficient, methyl donor enriched or standard diet during the perinatal period. These CC females were then crossed to a male from a different CC strain to produce reciprocal F1 hybrid females comprising 10 distinct genetic backgrounds. The adult F1 females were then tested in the open field, light/dark, stress-induced hyperthermia, forced swim and restraint stress assays. Our experimental design allowed us to estimate effects of genetic background, perinatal diet, PO and their interactions on behavior. Genetic background significantly affected all assessed phenotypes. Perinatal diet exposure interacted with genetic background to affect body weight, basal body temperature, anxiety-like behavior and stress response. In 8 of 9 genetic backgrounds, PO effects were observed on multiple phenotypes. Additionally, we identified a small number of diet-by-PO effects on body weight, stress response, anxiety- and depressive-like behavior. Our data show that rodent behaviors that model psychiatric disorders are affected by genetic background, PO and perinatal diet, as well as interactions among these factors.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.

BACKGROUND: Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function. METHODS AND SETTING: 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >10(4) colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed. RESULTS: Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis (p=0.005). DISCUSSION AND CONCLUSIONS: This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

Antibiotic Prophylaxis Regimens in Trauma and Orthopaedic Surgery: Are We Providing Adequate Cover Against Colonizing Organisms?

UNLABELLED: Trauma, elective orthopaedics, and an aging population will result in an increasing health burden and work load. The move to surgical podiatrists in the National Health Service within the United Kingdom will shift the surgical workload away from orthopaedic surgeons. A devastating complication of foot and ankle surgery is postoperative infection. While postoperative infection is multifactorial in etiology, concomitant diabetes mellitus increases the general risk of trauma and orthopaedic surgical site infections up to 8-fold. We therefore undertook a prospective study of our unit antibiotic prophylaxis regimes. Fifty patients participated. Swabs were obtained using aseptic technique from the plantar aspect of the feet, between the toes, and subsequently cultured on agar plates. Specimens were then incubated for 48 hours before being exposed to antibiotic plates. Cultured organisms were classified as susceptible to an antibiotic regimen if susceptibility to cefuroxime, or susceptibility to either drug of the flucloxacillin/gentamicin combination, was demonstrated. Statistical analysis e was performed. A P value <.05 was considered significant. Fifty patients were recruited, 26 (52%) were male. Mean age of 53 ± 19.4 years. The cohort included 15 diabetic, of which 11 (73.3%) insulin-dependent, and 35 nondiabetic patients. Comparing flucloxacillin/gentamicin against cefuroxime overall, susceptibility was noted in 84% and 70%, respectively (P = .096). Resistance to cefuroxime was significantly higher in diabetics than in nondiabetics (53% vs 25%, P = .046). The same pattern was observed for the flucloxacillin/gentamicin regimen (33% vs 9%, P = .049). While both regimens are active against colonizing organisms in this prospective observational study, flucloxacillin and gentamicin provide greater coverage overall. We have demonstrated that the use of flucloxacillin/gentamicin provides better coverage against commensal bacterial flora compared with cefuroxime alone. This is of even greater importance in the case of the specific high-risk subgroups, such as diabetic patients. LEVELS OF EVIDENCE: Level IV: Case Series.

From head to tail it's a 2 way street for neuro-immune communication.

Animals need to be able to rapidly and effectively respond to changes in their external and internal environment. To achieve this the nervous and immune systems need to coordinate their responses, integrating multiple cues including presence of potential pathogens, and availability of food. In our recent study (1) we demonstrate that signaling by sensory neurons in the head using the classical neurotransmitter serotonin can negatively regulate the rectal epithelial immune response upon infection of C. elegans with the naturally occurring bacterial pathogen Microbacterium nematophilum (M. nematophilum). The complicated nature of the mammalian brain and immune system has made it difficult to identify the molecular mechanisms mediating these interactions. With its simple, well described, nervous system and a rapidly growing understanding of its immune system, C. elegans has emerged as an excellent model to study the mechanisms by which animals recognize pathogens and coordinate behavioral and cellular immune responses to infection.

The impact of a PCR assay for candidemia on antifungal drug prescribing in critical care: an interrupted time series pilot study.

SUMMARY OBJECTIVE: To evaluate the feasibility of conducting a definitive study to assess the impact of introducing a rapid PCR-based test for candidemia on antifungal drug prescribing. METHOD: Prospective, single centre, interrupted time series study consisting of three periods of six months' duration. The assay was available during the second period, during which the PCR assay was available for routine use by physicians Monday-Friday with guaranteed 24-h turnaround time. For each period total antifungal drug use, expressed as treatment-days, was recorded and an adjustment was made to exclude estimated use for proven candidemia. Also, during the intervention period, antifungal prescribing decisions for up to 72 h after each PCR result became available were recorded as either concordant or discordant with that result. RESULTS: While overall antifungal use remained relatively stable throughout, after adjustment for candidemia, there was a 38% reduction in use following introduction of the PCR test; however, this was nonsignificant at the 95% level. During the intervention period overall concordance between the PCR result and prescribing decisions was 84%. CONCLUSIONS: The PCR assay for candidemia was requested, prescribing decisions were generally concordant with the results produced and there was an apparent decrease in antifungal prescription, although this was sustained even after withdrawal of the intervention; these findings should be more thoroughly evaluated in a larger trial.

Comparison of serum and whole-blood specimens for the detection of Candida DNA in critically ill, non-neutropenic patients.

In contrast to the multitude of studies on fungal PCR assay methods, little work has been reported evaluating Candida PCR performance when using whole blood compared with serum in candidaemic patients. Here, a comparison of the performance of whole-blood and serum specimens using a set of real-time PCR Candida species assays is described. Specimens were collected prospectively from non-neutropenic adults who were recruited to a diagnostic clinical trial, the primary purpose of which was to verify the performance of the assays using serum; in all, 104 participants also had whole-blood specimens submitted for analysis in addition to the serum specimen. Of these participants, 10 had laboratory-confirmed candidaemia and 94 were categorized as being 'unlikely' to have invasive Candida infection. PCR results from the whole-blood specimens are presented here and compared with the results from serum specimens in this subgroup among whom both specimen types were obtained contemporaneously. All participants with candidaemia were PCR-positive from serum samples; however, only seven were PCR-positive from whole blood. All specimens from patients in the 'unlikely' category were PCR-negative in both types of specimen. Moreover, DNA extraction from serum required 1 h; extraction from whole blood required approximately 3 h. These data tentatively suggest that, overall, serum is an appropriate specimen for Candida PCR for detection of candidaemia in non-neutropenic adults.

Evaluation of the VITEK 2 AST N-054 test card for the detection of extended-spectrum beta-lactamase production in Escherichia coli with CTX-M phenotypes.

OBJECTIVES: A new VITEK 2 antibiotic susceptibility testing (AST) card, AST N-054, was introduced for aerobic gram-negative bacilli in 2007 and has been widely adopted for routine use in the UK. We evaluated its performance for detecting extended-spectrum beta-lactamase (ESBL) production in Escherichia coli. METHODS: ESBL-producing faecal isolates of E. coli (n = 137) from residents in nursing homes were tested using the AST N-054 card on VITEK 2 and with MASTDISCS ID ESBL detection disc diffusion tests (Mast Diagnostics, Bootle, UK). The susceptibility result recommended by the VITEK 2 software was also recorded. RESULTS: The AST N-054 card detected ESBL production in 93 of the 137 isolates tested [test sensitivity 67.9% (95% CI, 59.7-75.1)]. E. coli strain A, a widespread lineage in the UK with a low-level CTX-M enzyme production, accounted for most of the detection failures, with 35/73 strain A isolates incorrectly reported versus 9/64 non-strain A isolates (P < 0.0001). The MASTDISCS correctly detected ESBL in 135/137 isolates [test sensitivity 98.5% (95% CI, 94.5-99.9)]. Of the 44 isolates found to be negative for ESBL production by VITEK 2, the Advanced Expert System misreported 29 as susceptible to cefotaxime and all as susceptible to ceftazidime and aztreonam. CONCLUSIONS: These data suggest that the AST N-054 card for the VITEK 2 system is less reliable than other previously reported cards for the detection of CTX-M beta-lactamase-producing E. coli circulating in the UK, particularly strain A isolates.

Deuterated gamma-malonic acid: its neutron crystal structure in relationship to other polymorphs of aliphatic dicarboxylic acids.

Three complete neutron diffraction datasets have been collected for deuterated malonic acid single crystals, DOOC(CD(2))COOD, above (153 K), just below (56 K) and further below (50 K) the low-temperature phase transition (T(c) = 57 K). The structural details obtained for this transition, studied previously solely by spectroscopic and calorimetric techniques, clearly establish its first-order nature. At 153 K, the space group is P\bar 1, Z = 2, Z' = 1. The molecules are packed as linear chains linked end-to-end by asymmetric hydrogen bonds so that the carboxyl groups form cyclic dimers. The deuterons in the carboxyl links are ordered. Neighboring chains are cross-linked through C-D...O hydrogen bonds. Upon cooling through the transition the cell doubles along the a axis. Molecules which are equivalent by symmetry above T(c) become independent below T(c) owing to conformational changes in alternate chains. At 50 K, the space group is P\bar 1, Z = 4, Z' = 2. Thermal motion analysis, using for all three temperatures the same segmented rigid-body model, reveals a large torsional motion around the one COOD group associated with the conformational change. Refinements were carried out on all three datasets with an anharmonic structural model, including higher-order displacement tensors (Gram-Charlier expansion up to fourth order). Only atoms involved in torsional motion exhibit a significant anharmonic component which increases with temperature.

A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults.

BACKGROUND: Invasive Candida infection among nonneutropenic, critically ill adults is a clinical problem that has received increasing attention in recent years. Poor performance of extant diagnostic modalities has promoted risk-based, preemptive prescribing in view of the poor outcomes associated with inadequate or delayed antifungal therapy; this risks unnecessary overtreatment. A rapid, reliable diagnostic test could have a substantial impact on therapeutic practice in this patient population. METHODS: Three TaqMan-based real-time polymerase chain reaction assays were developed that are capable of detecting the main medically important Candida species, categorized according to the likelihood of fluconazole susceptibility. Assay 1 detected Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida dubliniensis. Assays 2 and 3 detected Candida glabrata and Candida krusei, respectively. The clinical performance of these assays, applied to serum, was evaluated in a prospective trial of nonneutropenic adults in a single intensive care unit. RESULTS: In all, 527 specimens were obtained from 157 participants. All 3 assays were run in parallel for each specimen; they could be completed within 1 working day. Of these, 23 specimens were obtained from 23 participants categorized as having proven Candida infection at the time of sampling. If a single episode of Candida famata candidemia was excluded, the estimated clinical sensitivity, specificity, and positive and negative predictive values of the assays in this trial were 90.9%, 100%, 100% and 99.8%, respectively. CONCLUSIONS: These data suggest that the described assays perform well in this population for enhancing the diagnosis of candidemia. The extent to which they may affect clinical outcomes, prescribing practice, and cost-effectiveness of care remains to be ascertained.

Improving molecular detection of Candida DNA in whole blood: comparison of seven fungal DNA extraction protocols using real-time PCR.

The limitations of classical diagnostic methods for invasive Candida infections have led to the development of molecular techniques such as real-time PCR to improve diagnosis. However, the detection of low titres of Candida DNA in blood from patients with candidaemia requires the use of extraction methods that efficiently lyse yeast cells and recover small amounts of DNA suitable for amplification. In this study, a Candida-specific real-time PCR assay was used to detect Candida albicans DNA in inoculated whole blood specimens extracted using seven different extraction protocols. The yield and quality of total nucleic acids were estimated using UV absorbance, and specific recovery of C. albicans genomic DNA was estimated quantitatively in comparison with a reference (Qiagen kit/lyticase) method currently in use in our laboratory. The extraction protocols were also compared with respect to sensitivity, cost and time required for completion. The TaqMan PCR assay used to amplify the DNA extracts achieved high levels of specificity, sensitivity and reproducibility. Of the seven extraction protocols evaluated, only the MasterPure yeast DNA extraction reagent kit gave significantly higher total nucleic acid yields than the reference method, although nucleic acid purity was highest using either the reference or YeaStar genomic DNA kit methods. More importantly, the YeaStar method enabled C. albicans DNA to be detected with highest sensitivity over the entire range of copy numbers evaluated, and appears to be an optimal method for extracting Candida DNA from whole blood.

Food-poisoning and commercial air travel.

With the introduction of budget airlines and greater competitiveness amongst all airlines, air travel has now become an extremely popular form of travel, presenting its own unique set of risks from food poisoning. Foodborne illness associated with air travel is quite uncommon in the modern era. However, when it occurs, it may have serious implications for passengers and when crew are affected, has the potential to threaten safety. Quality, safe, in-flight catering relies on high standards of food preparation and storage; this applies at the airport kitchens (or at subcontractors' facilities), on the aircraft and in the transportation vehicles which carry the food from the ground source to the aircraft. This is especially challenging in certain countries. Several foodborne outbreaks have been recorded by the airline industry as a result of a number of different failures of these systems. These have provided an opportunity to learn from past mistakes and current practice has, therefore, reached such a standard so as to minimise risk of failures of this kind. This review examines: (i) the origin of food safety in modern commercial aviation; (ii) outbreaks which have occurred previously relating to aviation travel; (iii) the microbiological quality of food and water on board commercial aircraft; and (iv) how Hazard Analysis Critical Control Points may be employed to maintain food safety in aviation travel.