North Bristol NHS Trust

About: North Bristol NHS Trust is a healthcare organization based out in Bristol, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 2204 authors who have published 2811 publications receiving 61110 citations.

Bacterial Strain-to-Strain Variation in Pharmacodynamic Index Magnitude, a Hitherto Unconsidered Factor in Establishing Antibiotic Clinical Breakpoints

Abstract: Antibiotic pharmacodynamic modeling allows variations in pathogen susceptibility and human pharmacokinetics to be accounted for when considering antibiotic doses, potential bacterial pathogen targets for therapy, and clinical susceptibility breakpoints. Variation in the pharmacodynamic index (area-under-the-concentration curve to 24 h [AUC24]/MIC; maximum serum concentration of drug in the serum/MIC; time the serum concentration remains higher than the MIC [T > MIC]) is not usually considered. In an in vitro pharmacokinetic model of infection using a dose-ranging design, we established the relationship between AUC24/MIC and the antibacterial effect for moxifloxacin against 10 strains of Staphylococcus aureus. The distributions of AUC24/MIC targets for 24-h bacteriostatic effect and 1-log, 2-log, and 3-log drops in bacterial counts were used to calculate potential clinical breakpoint values, and these were compared with those obtained by the more conventional approach of taking a single AUC24/MIC target. Consideration of the AUC24/MIC as a distribution rather than a single value resulted in a lower clinical breakpoint.

Radical prostatectomy for locally advanced and metastatic prostate cancer

Abstract: The management of advanced prostate cancer remains challenging. Traditionally, radical prostatectomy was discouraged in patients with locally advanced or node positive disease owing to the increased complication rate and treatment related morbidity. However, technical advances and refinements in surgical techniques have enabled the outcomes for patients with high risk prostate cancer to be improved. More recently, the concept of cytoreductive prostatectomy has been described where surgery (often Combined with an extended lymph node dissection) is performed in the setting of metastatic disease. Indirect evidence suggests an advantage using the cytoreductive approach. Hypothetical explanations for this observed benefit include decreased tumour burden, immune modulation, improved response to secondary treatment and avoidance of secondary complications attributable to local tumour growth. Nevertheless, prospective trials are required to investigate this further.

Throat swabs in children with respiratory tract infection: associations with clinical presentation, and potential targets for point-of-care testing

Abstract: Background and objectives Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. Results At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52-0.56)] or ≥1 virus [0.64 (95% CI 0.61-0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation [AUROC 0.80 (0.77-0.84)]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P < 0.001) than bacteria (56% versus 40%, P = 0.01); greatest reductions seen in RSV, influenza B and Haemophilus influenzae. Conclusion Findings demonstrate that clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial.

Prophylactic use of oxytocin at caesarean section: where are the guidelines?

Abstract: Oxytocin, a polypeptide hormone produced by the posterior pituitary gland, was first synthesised by Vincent du Vigneaud, an American biochemist in the 1950s [1]. He was subsequently awarded the Nobel Prize for Chemistry for this and other work. Syntocinon , its synthetic analogue, was introduced into medical practice in the late 1950s and its dose, administration and clinical applications have been the subject of debate ever since. The findings of a UK-wide survey into the administration of oxytocin, published in this issue of the Journal, highlights continued variation in practice throughout the UK, and the authors call for national protocols to guide dosing [2]. Postpartum haemorrhage remains a significant cause of maternal morbidity [3] and the use of oxytocin has reduced maternal morbidity worldwide [4]. However, use of oxytocin is not without its own problems as it can cause significant maternal side effects [5, 6]. Hypotension and tachycardia are common, and electrocardiographic changes suggestive of myocardial ischaemia may occur [7]. Maternal death related to oxytocin administration is documented in the Confidential Enquiries into Maternal Deaths, 1997–99 [8]. The varied oxytocin dosing regimens used throughout the UK have been a subject of increased interest over the last decade. In 2001, a national survey found that 87% of responding UK lead obstetric anaesthetists were using a dose of 10 IU oxytocin, 50% by rapid intravenous bolus [9]. A repeat of the same survey a year later indicated that only 15% of respondents were using a 10-IU dose, and only 23% of these by rapid bolus [9]. A welcome finding of this current survey by West et al. is that an initial 10-IU oxytocin bolus has completely disappeared from UK practice. Current guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) [10] and the British National Formulary [11] recommend the use of 5 IU oxytocin as a ‘slow bolus’, although the timescale over which it should be administered is not specified. Bolus dosing is associated with significantly more cardiovascular sideeffects than if administered over 5 minutes, for both 5 IU and 3 IU oxytocin [12, 13]. Reducing the dose of the oxytocin bolus may not be the key to reducing side-effects: even doses between 0.5 IU and 3 IU have been shown to produce hypotension in 20-30% of patients when given as a bolus [14]. It may be that reducing the speed of drug delivery is the most important factor for reducing potentially dangerous side-effects, and this is especially important in those at high risk due to cardiac disease or hypovolaemia. Some centres do not use a traditional ‘bolus’ of oxytocin but commence a prophylactic oxytocin infusion. A Canadian study of 40 patients found that the ED90 of oxytocin infusion required to produce adequate uterine contraction three minutes after delivery was 0.29 IU.min 1 in a low-risk population undergoing elective caesarean delivery [15]. What evidence base is there to guide oxytocin doses? In the mid2000s, two studies published data on a range of oxytocin doses used at caesarean section and estimated a minimum effective dose (ED90) for oxytocin after both elective caesarean section [16] and caesarean after labour [17]. The primary endpoint used was uterine tone, subjectively assessed by a blinded obstetrician. The ED90 of oxytocin at elective caesarean was calculated as 0.35 IU

Does Routine Postoperative Computerized Tomography After Acetabular Fracture Fixation Affect Management

Abstract: INTRODUCTION AND AIMS The use of routine postoperative computerized tomography (CT) scan after acetabular fracture reconstruction remains controversial. CT scan may provide more accurate detail regarding metalwork position, retained intra-articular fragments, and quality of reduction but does expose the patient to additional radiation dosage and incurs increased cost. The aim of this study was to evaluate a protocol of routine postoperative CT scan for all acetabular fractures after surgical fixation and assess the effect this has on patient management. PATIENTS AND METHODS The perioperative fluoroscopic images and postoperative plain radiographs of 122 patients who underwent surgical stabilization of a displaced acetabular fracture were reviewed and categorized into 3 groups: (1) safe, when there was no suspicion of metalwork malposition or intra-articular fragments; (2) inconclusive, when it was not possible to exclude malposition; or (3) definite malposition or intra-articular penetration of implants. The findings were compared with postoperative CT scans. The quality of reduction of the acetabular fracture was graded on plain radiographs using the Matta criteria and compared with the CT scan using a standardized technique. RESULTS Fractures that were categorized as safe on plain radiographs were confirmed to have no metalwork malposition on CT scan in 94% of the cases, with the other 6% having insignificant findings that did not require revision surgery. When plain radiographs were inconclusive (n = 17), 4 patients had metalwork malposition documented on CT scan and 2 of these required revision surgery. There was an increased risk of implant malposition with use of spring plates for posterior wall stabilization. There was significant variation between the quality of reduction when assessed with plain radiographs as compared with CT scans (P < 0.001). In 42% of the patients who were thought to have anatomic reduction on plain radiographic assessment, the reduction was either imperfect or poor based on CT assessment. CONCLUSIONS CT scans were more accurate than plain radiographs in detecting metalwork malposition and in assessing quality of reduction of the acetabular fracture. The use of postoperative CT scans may be restricted to a group of fractures that have inconclusive or definite malpositioning of implants on perioperative or postoperative radiographs, especially with use of spring pates or to those patients in whom quality of reduction needs more accurate assessment for quality assurance or prognostic reasons. LEVEL OF EVIDENCE Level IV; Diagnostic -Investigating a diagnostic test.