Fifteen-minute consultation: Time Out as an alternative to toxic debrief.

Debriefing is well established in healthcare teams after acute events, with a focus on clinical learning, improving practice and performance; however, the term is perceived by psychologists as something quite different. This article describes the Time Out model as a standardised method of providing support to staff after events that may cause distress. In addition to exploring clinical issues, the model aims to promote peer support networks, educate staff regarding common reactions to traumatic events and signpost to other sources of support.

Palliative radiotherapy: survival prognostic factors - single-centre retrospective cohort study.

OBJECTIVE: Patients with non-curative malignancy can receive palliative radiotherapy (PR) to alleviate symptoms. However, choosing the right patient to receive PR can be challenging, as some patients may not survive long enough to gain benefit. This study aims to identify prognostic factors for overall survival (OS) and 30-day mortality (30DM) following PR and to test these in a real-world cohort. METHOD: A retrospectively collected data set of all adults completing PR between 1 August 2018 and 31 December 2018 at a single centre (n=214, Southend University Hospital NHS Foundation Trust, UK) was used to test prognostic factors. Factors such as demographics, tumour primary, treatment area, fractionation regime, performance status (PS), progressive disease (PD), opioid or steroid use and haemoglobin level, as well as overall survival, were collected. Cox regression was used to examine survival predictors, and logistic regression was used to determine the predictive strength of factors for 30DM. RESULTS: Overall 30DM was 14%. There was significantly worse survival in patients with poor PS (HR 1.2406, 95% CI 0.94 to 1.64. p=0.01). Patients with PS 3 had a median OS of 75 days and were more likely to experience 30DM (OR 6.2, 95% CI 1.226 to 45.42, p=0.03). Patients with PD outside of the radiation field (46%, 30 out of 65 documented) had significantly worse OS (HR 5.24, 95% CI 2.19 to 12.5, p<0.001). CONCLUSION: Poor PS and PD were prognostic of OS and 30DM. Future work should include validation with a prospectively collected cohort.

Major trauma and urban cyclists: physiological status and injury profile.

INTRODUCTION: Pedal cycling in cities has the potential to deliver significant health and economic benefits for individuals and society. Safety is the main concern for potential cyclists although the statistical risk of death is low. Little is known about the severity of injuries sustained by city cyclists and their outcome. AIM: The aim of this study was to characterise the physiological status and injury profile of cyclists admitted to our urban major trauma centre (MTC). METHODS: Database analysis of cyclist casualties between 2004 and 2009. The physiological parameters examined were admission systolic blood pressure (SBP), admission base deficit and prehospital Glasgow Coma Scale. RESULTS: 265 cyclists required full trauma-team activation. 82% were injured during a collision with a motorised vehicle. The majority (73%) had collided with a car or a heavy goods vehicle (HGV). These casualties formed the cohort for further analysis. Cyclists who collided with an HGV were more severely injured and had a higher mortality rate. Low SBP and high base deficit indicate that haemorrhagic shock is a key feature of HGV casualties. CONCLUSION: Collision with any vehicle can result in death or serious injury to a cyclist. Injury patterns vary with the type of vehicle involved. HGVs were associated with severe injuries and death as a result of uncontrollable haemorrhage. Awareness of this injury profile may aid prehospital management and expedite transfer to MTC care. Rapid haemorrhage control may salvage some, but not all, of these casualties. The need for continued collision prevention strategies and long-term outcome data collection in trauma patients is highlighted.

Visual scanning in the recognition of facial affect: is there an observer sex difference?

This investigation assessed whether differences exist in the way males and females overtly orient their visual attention to salient facial features while viewing static emotional facial expressions. Eye movements were recorded while fifty healthy participants (23 males, 27 females) viewed a series of six universal facial expressions. Groups were compared with respect to accuracy and reaction time in emotional labeling. The number and duration of foveal fixations to four predefined facial areas of interest (AOIs)--each eye, nose, mouth--were also recorded. There were no significant group differences with respect to accuracy (p = 0.997), though females were significantly faster than males in correctly identifying expressions (p = 0.047). Analysis of the visual scan path revealed that while both groups spent more time and looked more frequently at the eye region, males spent significantly more time viewing the nose and mouth. The duration and number of fixations made to the nose were significantly greater in males (p < 0.05). This study is the first to show reaction time differences between the sexes across a range of universal emotions. Further, this is the first work to suggest the orienting of attention to the lower part of the face, especially the nose, appears to differentiate the sexes.

Perineal recurrence of prostate cancer post-brachytherapy.

We present a rare case of perineal recurrence of prostate cancer post low dose rate brachytherapy. Increased levels of prostate-specific antigen were recorded 12 years post brachytherapy. Pelvic CT and MRI visualized a nodular lesion in the perineum, and positron emission tomography demonstrated choline-avidity. Ultrasound-guided biopsy of the nodule was performed, yielding histology consistent with prostatic adenocarcinoma. Metastatic prostatic seeding to the perineum is a rare complication of brachytherapy. We discuss the putative mechanism, approach to diagnosis, and management.

Mupirocin H, a novel metabolite resulting from mutation of the HMG-CoA synthase analogue, mupH in Pseudomonas fluorescens.

Mutation of the HMG-CoA synthase encoding mupH gene in Pseudomonas fluorescens gives rise to a new metabolite formed from a truncated polyketide intermediate, providing in vivo evidence for the roles of mupH and cognate genes found in several "AT-less" and other bacterial PKS gene clusters responsible for the biosynthesis of diverse metabolites containing acetate/propionate derived side chains.

Shift to Pseudomonic acid B production in P. fluorescens NCIMB10586 by mutation of mupirocin tailoring genes mupO, mupU, mupV, and macpE.

Mupirocin, a polyketide-derived antibiotic from Pseudomonas fluorescens NCIMB10586, is a mixture of pseudomonic acids (PA) that target isoleucyl-tRNA synthase. The mup gene cluster encodes both type I polyketide synthases and monofunctional enzymes that should play a role during the conversion of the product of the polyketide synthase into the active antibiotic (tailoring). By in-frame deletion analysis of selected tailoring open-reading frames we show that mupQ, mupS, mupT, and mupW are essential for mupirocin production, whereas mupO, mupU, mupV, and macpE are essential for production of PA-A but not PA-B. Therefore, PA-B is not simply produced by hydroxylation of PA-A but is either a precursor of PA-A or a shunt product. In the mupW mutant, a new metabolite lacking the tetrahydropyran ring is produced, implicating mupW in oxidation of the 16-methyl group.

Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586.

The polyketide antibiotic mupirocin (pseudomonic acid) produced by Pseudomonas fluorescens NCIMB 10586 competitively inhibits bacterial isoleucyl-tRNA synthase and is useful in controlling Staphylococcus aureus, particularly methicillin-resistant Staphylococcus aureus. The 74 kb mupirocin biosynthesis cluster has been sequenced, and putative enzymatic functions of many of the open reading frames (ORFs) have been identified. The mupirocin cluster is a combination of six larger ORFs (mmpA-F), containing several domains resembling the multifunctional proteins of polyketide synthase and fatty acid synthase type I systems, and individual genes (mupA-X and macpA-E), some of which show similarity to type II systems (mupB, mupD, mupG, and mupS). Gene knockout experiments demonstrated the importance of regions in mupirocin production, and complementation of the disrupted gene confirmed that the phenotypes were not due to polar effects. A model for mupirocin biosynthesis is presented based on the sequence and biochemical evidence.

Mupirocin W, a novel pseudomonic acid produced by targeted mutation of the mupirocin biosynthetic gene cluster.

Mutation of the mupW gene in the mupirocin biosynthetic gene cluster in Pseudomonas fluorescens results in efficient production of a novel pseudomonic acid metabolite, mupirocin W, which lacks the characteristic tetrahydropyran ring, and reveals the role of the mupW gene in pseudomonic acid biosynthesis.

Children with human immunodeficiency virus admitted to a paediatric intensive care unit in the United Kingdom over a 10-year period.

OBJECTIVE: There is little published experience regarding the outcome of children with human immunodeficiency virus (HIV) infection treated on a paediatric intensive care unit (PICU). We describe the outcome of children with HIV infection in our hospital over a 10-year period. METHOD: We performed a retrospective analysis of all children with HIV infection admitted to our PICU between August 1992 and July 2002. Their ages ranged from 2 months to 11 years (median 4 months). Information collected included demographic data, clinical presentation, investigations, treatment and outcome. RESULTS: There were 42 children with HIV infection admitted to PICU during the study period, with 66 admission episodes. Sixteen (38%) children died in PICU, and 26 (62%) survived their last PICU admission. Of these, 5 died at a later date (between 1 and 32 months after discharge from PICU) and 21 survived to the time of reporting. The most frequent reason for PICU admission was respiratory failure, due either to Pneumocystis carinii pneumonia (45% of admissions) or to other respiratory pathogens (32%). Over 80% of current survivors had good outcomes in terms of growth and development; 6 children had evidence of spastic diplegia. CONCLUSIONS: Although there is significant mortality among children with HIV infection admitted to PICU, many of them survive their admission, and over 80% of the survivors have good outcomes with the currently available highly active anti-retroviral therapy. This provides evidence that intensive care treatment is appropriate for this group of patients in the United Kingdom.

Mutational analysis reveals that all tailoring region genes are required for production of polyketide antibiotic mupirocin by pseudomonas fluorescens: pseudomonic acid B biosynthesis precedes pseudomonic acid A.

The Pseudomonas fluorescens mupirocin biosynthetic cluster encodes six proteins involved in polyketide biosynthesis and 26 single polypeptides proposed to perform largely tailoring functions. In-frame deletions in the tailoring open reading frames demonstrated that all are required for mupirocin production. A bidirectional promoter region was identified between mupF, which runs counter to other open reading frames and its immediate neighbor macpC, implying the 74-kb cluster consists of two transcriptional units. mupD/E and mupJ/K must be cotranscribed as pairs for normal function implying co-assembly during translation. MupJ and K belong to a widely distributed enzyme pair implicated, with MupH, in methyl addition. Deletion of mupF, a putative ketoreductase, produced a mupirocin analogue with a C-7 ketone. Deletion of mupC, a putative dienoyl CoA reductase, generated an analogue whose structure indicated that MupC is also implicated in control of the oxidation state around the tetrahydropyran ring of monic acid. Double mutants with DeltamupC and DeltamupO, DeltamupU, DeltamupV, or DeltamacpE produced pseudomonic acid B but not pseudomonic acid A, as do the mupO, U, V, and macpE mutants, indicating that MupC must work after MupO, U, and V.

Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children.

RATIONALE: Rebound pulmonary hypertension (PHT) can complicate the weaning of nitric oxide (NO), and is in part related to transient depletion of intrinsic cyclic guanosine monophosphate. Rebound is characterized by increased pulmonary arterial (PA) pressure, cardiopulmonary instability, and in some cases, the need to continue NO beyond the intended period of use. There is anecdotal evidence that sildenafil, a phosphodiesterase-5 inhibitor, may prevent recurrence of rebound. OBJECTIVES: We investigated the role of sildenafil in preventing rebound (an increase in PA pressure of 20% or greater, or failure to discontinue NO) in patients in whom previous attempts had not been made to wean from NO. METHODS: Thirty ventilated infants and children, receiving 10 ppm or greater inhaled NO, were randomized to receive 0.4 mg/kg of sildenafil, or placebo, 1 h before discontinuing NO. Twenty-nine patients completed the study. MEASUREMENTS: PA pressures and blood gases were measured before the study drug, and 1 and 4 h after stopping NO. MAIN RESULTS: Rebound occurred in 10 of 14 placebo patients, and 0 of 15 sildenafil patients (p < 0.001). PA pressure increased by 25% (14-67) in placebo patients, and by 1%(-9-5) in sildenafil patients (p < 0.001). Four placebo patients could not be weaned from NO due to severe cardiovascular instability, whereas all sildenafil patients were weaned (p = 0.042). Duration of ventilation after study was 98.0 (47.0-223.5) h for placebo patients and 28.2 (15.7-54.6) h for sildenafil patients (p = 0.024). CONCLUSION: A single dose of sildenafil prevented rebound after withdrawal of NO, and reduced the duration of mechanical ventilation. Prophylaxis with sildenafil should be considered when weaning patients from inhaled NO.