Ease and comfort of pre-oxygenation with high-flow nasal oxygen cannulae vs. facemask: a randomised controlled trial.

The Difficult Airway Society recommends that all patients should be pre-oxygenated before the induction of general anaesthesia, but this may not always be easy or comfortable and anaesthesia may often be induced without full pre-oxygenation. We tested the hypothesis that high-flow nasal oxygen cannulae would be easier and more comfortable than facemasks for pre-oxygenation. We randomly allocated 199 patients undergoing elective surgery aged ≥ 10 years to pre-oxygenation using either high-flow nasal oxygen or facemask. Ease and comfort were assessed by anaesthetists and patients on 10-cm visual analogue scale and six-point smiley face scale, respectively. Secondary endpoints included end-tidal oxygen fraction after securing a definitive airway and time to secure an airway. A mean difference (95%CI) between groups in ratings of -0.76 (-1.25 to -0.27) cm for ease of use (p = 0.003) and -0.45 (-0.75 to -0.13) points for comfort (p = 0.006), both favoured high-flow nasal oxygen. A mean difference (95%CI) between groups in end-tidal oxygen fraction of 3.89% (2.41-5.37%) after securing a definitive airway also favoured high-flow nasal oxygen (p < 0.001). There was no significant difference between groups in the number of patients with hypoxaemia (Sp O2 < 90%) or severe hypoxaemia (Sp O2 < 85%) lasting ≥ 1 min or ≥ 2 min; in the proportion of patients with an end-tidal oxygen fraction < 87% in the first 5 min after tracheal intubation (52.2% vs. 58.9% in facemask and high-flow nasal oxygen groups, respectively; p = 0.31); or in time taken to secure an airway (11.6 vs. 12.2 min in facemask and high-flow nasal oxygen groups, respectively; p = 0.65). In conclusion, we found pre-oxygenation with high-flow nasal oxygen to be easier for anaesthetists and more comfortable for patients than pre-oxygenation with a facemask, with no clinically relevant differences in end-tidal oxygen fraction after securing a definitive airway or time to secure an airway. The differences in ease and comfort were modest.

A retrospective audit of postoperative days alive and out of hospital, including before and after implementation of the WHO surgical safety checklist.

We implemented the World Health Organization surgical safety checklist at Auckland City Hospital from November 2007. We hypothesised that the checklist would reduce postoperative mortality and increase days alive and out of hospital, both measured to 90 postoperative days. We compared outcomes for cohorts who had surgery during 18-month periods before vs. after checklist implementation. We also analysed outcomes during 9 years that included these periods (July 2004-December 2013). We analysed 9475 patients in the 18-month period before the checklist and 10,589 afterwards. We analysed 57,577 patients who had surgery from 2004 to 2013. Mean number of days alive and out of hospital (95%CI) in the cohort after checklist implementation was 1.0 (0.4-1.6) days longer than in the cohort preceding implementation, p < 0.001. Ninety-day mortality was 395/9475 (4%) and 362/10,589 (3%) in the cohorts before and after checklist implementation, multivariable odds ratio (95%CI) 0.93 (0.80-1.09), p = 0.4. The cohort changes in these outcomes were indistinguishable from longer-term trends in mortality and days alive and out of hospital observed during 9 years, as determined by Bayesian changepoint analysis. Postoperative mortality to 90 days was 228/5686 (4.0%) for Maori and 2047/51,921 (3.9%) for non-Maori, multivariable odds ratio (95%CI) 0.85 (0.73-0.99), p = 0.04. Maori spent on average (95%CI) 1.1 (0.5-1.7) fewer days alive and out of hospital than non-Maori, p < 0.001. In conclusion, our patients experienced improving postoperative outcomes from 2004 to 2013, including the periods before and after implementation of the surgical checklist. Maori patients had worse outcomes than non-Maori.

A toolbox for the longitudinal assessment of healthspan in aging mice.

The number of people aged over 65 is expected to double in the next 30 years. For many, living longer will mean spending more years with the burdens of chronic diseases such as Alzheimer's disease, cardiovascular disease, and diabetes. Although researchers have made rapid progress in developing geroprotective interventions that target mechanisms of aging and delay or prevent the onset of multiple concurrent age-related diseases, a lack of standardized techniques to assess healthspan in preclinical murine studies has resulted in reduced reproducibility and slow progress. To overcome this, major centers in Europe and the United States skilled in healthspan analysis came together to agree on a toolbox of techniques that can be used to consistently assess the healthspan of mice. Here, we describe the agreed toolbox, which contains protocols for echocardiography, novel object recognition, grip strength, rotarod, glucose tolerance test (GTT) and insulin tolerance test (ITT), body composition, and energy expenditure. The protocols can be performed longitudinally in the same mouse over a period of 4-6 weeks to test how candidate geroprotectors affect cardiac, cognitive, neuromuscular, and metabolic health.

Haemodynamic profiles of etomidate vs propofol for induction of anaesthesia: a randomised controlled trial in patients undergoing cardiac surgery.

BACKGROUND: Etomidate is frequently selected over propofol for induction of anaesthesia because of a putatively favourable haemodynamic profile, but data confirming this perception are limited. METHODS: Patients undergoing cardiac surgery were randomised to induction of anaesthesia with propofol or etomidate. Phase I (n=75) was conducted as open-label, whereas Phase II (n=75) was double blind. Mean arterial blood pressure (MAP) and boluses of vasopressor administered after induction were recorded. The primary endpoint was the area under the curve below baseline MAP (MAP-time integral) during the 10 min after induction. Secondary endpoints were the use of vasopressors over the same period, and the effect of blinding on the aforementioned endpoints. Groups were compared using regression models with phase and anaesthetist as factors. RESULTS: The mean difference between etomidate and propofol in the MAP-time integral below baseline was 2244 mm Hg s (95% confidence interval, 581-3906; P=0.009), representing a 34% greater reduction with propofol. Overall, vasopressors were used in 10/75 patients in the etomidate group vs 21/75 in the propofol group (P=0.38), and in 20/74 patients during the blinded phase vs 11/76 during the open-label phase (P=0.31). The interaction between randomisation and phase (open-labelled or blinded) was not significant for either primary (P=0.73) or secondary endpoints (P=0.90). CONCLUSIONS: Propofol caused a 34% greater reduction in MAP-time integral from baseline after induction of anaesthesia than etomidate, despite more frequent use of vasopressors with propofol, confirming the superior haemodynamic profile of etomidate in this context. The proportion of patients receiving vasopressors increased slightly, albeit not significantly, in both groups in the blinded phase. CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000717651.

The incidence of hyperthermia during craniotomy.

There is evidence that even mild hyperthermia may exacerbate brain injury. There seem reasonable grounds for considering patients undergoing craniotomy as at risk for brain injury. A retrospective observational study was undertaken to measure the incidence of mild hyperthermia in craniotomy cases in which the patient was initially normothermic. Auckland City Hospital's database of electronic anaesthetic records was searched for adult patients who were normothermic (≤37°C) prior to undergoing craniotomy procedures. For each case, demographic data, intraoperative naso- or oropharyngeal temperature measurements, and paracetamol use were extracted. We identified the proportion of patients whose temperature rose to exceed normal (>37°C) and subdivided that group into the proportion in whom the temperature rose to ≥38°C. Two thousand, nine hundred and thirty-five craniotomy cases began their operations while normothermic and had adequate temperature data collected. There were 984 (33.5%) cases that had at least one temperature reading >37°C, for a mean (standard deviation [SD]) time of 66.0 (64.6) minutes, and 49 (1.7%) cases that had at least one reading ≥38°C for a mean (SD) time of 40.4 (38.1) minutes. The majority (77.8%) who became mildly hyperthermic remained so at the end of the procedure. New mild hyperthermia occurs commonly during craniotomy. In view of the compelling evidence of potential harm arising from mild hyperthermia in brain injury, these findings suggest an opportunity for practice improvement in the anaesthetic management of craniotomy patients. Reasonable steps should be taken by anaesthetists to avoid intraoperative hyperthermia of any degree.

Endogenous neurosteroids influence synaptic GABAA receptors during postnatal development.

GABA plays a key role in both embryonic and neonatal brain development. For example, during early neonatal nervous system maturation, synaptic transmission, mediated by GABAA receptors (GABAA Rs), undergoes a temporally specific form of synaptic plasticity to accommodate the changing requirements of maturing neural networks. Specifically, the duration of miniature inhibitory postsynaptic currents (mIPSCs), resulting from vesicular GABA activating synaptic GABAA Rs, is reduced, permitting neurones to appropriately influence the window for postsynaptic excitation. Conventionally, programmed expression changes to the subtype of synaptic GABAA R are primarily implicated in this plasticity. However, it is now evident that, in developing thalamic and cortical principal- and inter-neurones, an endogenous neurosteroid tone (eg, allopregnanolone) enhances synaptic GABAA R function. Furthermore, a cessation of steroidogenesis, as a result of a lack of substrate, or a co-factor, appears to be primarily responsible for early neonatal changes to GABAergic synaptic transmission, followed by further refinement, which results from subsequent alterations of the GABAA R subtype. The timing of this cessation of neurosteroid influence is neurone-specific, occurring by postnatal day (P)10 in the thalamus but approximately 1 week later in the cortex. Neurosteroid levels are not static and change dynamically in a variety of physiological and pathophysiological scenarios. Given that GABA plays an important role in brain development, abnormal perturbations of neonatal GABAA R-active neurosteroids may have not only a considerable immediate, but also a longer-term impact upon neural network activity. Here, we review recent evidence indicating that changes in neurosteroidogenesis substantially influence neonatal GABAergic synaptic transmission. We discuss the physiological relevance of these findings and how the interference of neurosteroid-GABAA R interaction early in life may contribute to psychiatric conditions later in life.

Deep and profound hypothermia in haemorrhagic shock, friend or foe? A systematic review.

INTRODUCTION: Survival in exsanguinating cardiac arrest patients is poor, as is neurological outcome in survivors. Hypothermia has traditionally been seen as harmful to trauma patients and associated with increased mortality; however, there has been speculation that cooling to very low temperatures (≤20°C) could be used to treat haemorrhagic trauma patients by the induction of a suspended animation period through extreme cooling, which improves survival and preserves neurological function. This has been termed emergency preservation and resuscitation (EPR). METHODS: A systematic review of the literature was used to examine the evidence base behind the use of deep and profound hypothermia in haemorrhagic shock (HS). It included original research articles (human or animal) with cooling to ≤20°C after HS or an experimental model replicating it. Normovolaemic cardiac arrest, central nervous system injury and non-HS models were excluded. RESULTS: Twenty articles using 456 animal subjects were included, in which 327 were cooled to ≤20°C. All studies describing good survival rates were possible using EPR and 19/20 demonstrated that EPR can preserve neurological function after prolonged periods of circulatory arrest or minimal circulatory flow. This additional period can be used for surgical intervention to arrest haemorrhage in HS that would otherwise be lethal. CONCLUSIONS: The outcomes of this review have significant implications for application to human patients and the ongoing human clinical trial (EPR for Cardiac Arrest from Trauma). Current evidence suggests that hypothermia ≤20°C used in the form of EPR could be beneficial to the HS patient.

Role of GABAA receptor subtypes in the behavioural effects of intravenous general anaesthetics.

Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target. Advances in molecular pharmacology and in genetic manipulation of rodent genes reveal that different subtypes of the GABAA receptor are responsible for mediating particular aspects of the anaesthetic behavioural repertoire. Such studies provide a better understanding of the neuronal circuitry involved in the various anaesthetic-induced behaviours and, in the future, may result in the development of novel therapeutics with a reduced propensity for side-effects.

Teaching and learning in undergraduate anaesthesia: a quantitative and qualitative analysis of practice at the University of Auckland.

Anaesthesia encompasses a broad range of knowledge and skills of relevance to graduating doctors. For the majority of new doctors, an undergraduate clinical rotation is their only exposure to anaesthesia practice. However, the content and approach to undergraduate anaesthesia education varies between institutions. We explored our students' views and experiences, and teaching approaches and expectations of consultant anaesthetists during a clinical attachment in anaesthesia. Our mixed-method design included student and staff surveys, logbook analysis and student focus groups. Logbook analysis of all 202 students showed mean numbers of attempts for bag-mask ventilation, laryngeal mask insertion, tracheal intubation and IV cannulation were 6.8, 3.9, 3.3 and 4.5, respectively. Focus group responses (11 students, three groups) suggested a mismatch between students' expectations of performing clinical skills and the available opportunities, particularly for IV cannulation. Students often felt reluctant to ask anaesthetists to teach them, and appreciated clinician-led engagement in all aspects of learning patient management. Among the 78 anaesthetists (29.3%) responding to the survey, the five tasks most frequently identified as suitable for teaching to students all related to airway management. Our study found much unanticipated variability in student exposure, teaching practice and attitudes to teaching various skills or procedures between anaesthetists, and student opinion of their clinical attachment. The findings resulted in a review of many aspects of the attachment. It is likely that other institutions will have similar variability and we recommend they undertake similar exercises to optimise teaching and learning opportunities for undergraduate anaesthesia.

Acute alcohol intoxication and bispectral index monitoring.

BACKGROUND: Bispectral index (BIS) monitoring is commonly used to decrease the risk of awareness during anaesthesia. We aimed to determine the relationship between blood alcohol concentration and brain function (as measured by BIS) in healthy adults. METHODS: In this prospective observational study, 21 anaesthetic registrars self-regulated alcohol consumption over a 3-h period. Expired alcohol concentration (breathalyser) and BIS measurements were performed hourly for 4 h. A venous blood alcohol sample was taken at the conclusion of the study period. RESULTS: The main outcome measures were the correlation between blood alcohol and brain function as measured by BIS and the change in BIS from baseline (∆BIS) at 4 h. The median number of standard drinks consumed was 9.1 (IQR 7.7-12.3), range 5.4-17. At 4 h, there was a moderate inverse correlation between BIS and blood alcohol (r = -0.49, P = 0.029) and between ∆BIS and blood alcohol (r = -0.46, P =0.043). CONCLUSION: In healthy young adults, we found a moderate correlation between venous blood alcohol concentration and BIS. This suggests that acute alcohol consumption can decrease BIS. This information may be relevant when providing anaesthesia to intoxicated patients who require urgent or time-critical surgery, although certain limitations of this study should be kept in mind.

Reduced embolic load during clinical cardiopulmonary bypass using a 20 micron arterial filter.

OBJECTIVE: To compare the efficiency of 20 and 40 µm arterial line filters during cardiopulmonary bypass for the removal of emboli from the extracorporeal circuit. METHODS: Twenty-four adult patients undergoing surgery were perfused using a cardiopulmonary bypass circuit containing either a 20 µm or 40 µm arterial filter (n = 12 in both groups). The Emboli Detection and Classification system was used to count emboli upstream and downstream of the filter throughout cardiopulmonary bypass. The mean proportion of emboli removed by the filter was compared between the groups. RESULTS: The 20 µm filter removed a significantly greater proportion of incoming emboli (0.621) than the 40 µm filter (0.334) (p=0.029). The superiority of the 20 µm filter persisted across all size groups of emboli larger than the pore size of the 40 µm filter. CONCLUSION: The 20 µm filter removed substantially more emboli than the 40 µm filter during cardiopulmonary bypass in this comparison.

A prospective, observational study of the effects of implementation strategy on compliance with a surgical safety checklist.

BACKGROUND: The reported benefits of using the WHO Surgical Safety Checklist (SSC) are likely to depend on compliance with its correct use. Compliance with SSC administration in centres that have introduced the checklist under a research protocol may differ from centres where the SSC is introduced independently. OBJECTIVE: To compare compliance with SSC administration at an original WHO pilot study centre (Hospital 1) with that at a similar neighbouring hospital (Hospital 2) that independently integrated the SSC with pre-existing practice. METHODS: This was a prospective, observational study. One hundred operations were observed at each hospital. We recorded: compliance with administration of SSC domains (Sign In, Time Out and Sign Out) and individual domain items; timing of domain administration; and operating room team engagement during administration. RESULTS: Domain compliance at Hospital 1 and Hospital 2, respectively, was: 96% and 31% (p<0.0005) for Sign In; 99% and 48% (p<0.0005) for Time Out and 22% and 9% (p=0.008) for Sign Out. Engagement of two or more teams during Sign In and Time Out occurred more frequently at Hospital 2 than at Hospital 1. DISCUSSION: Compliance with administration of SSC domains was lower at Hospital 2 which introduced the SSC outside the context of a strict study protocol. This finding mandates caution in extrapolation of benefits identified in SSC studies to non-study hospitals. Staff engagement was better at Hospital 2 where checklist administration leadership is strategically shared among anaesthetic, surgical and nursing team members as compared with exclusive nursing leadership at Hospital 1. STUDY REGISTRY NUMBER: Australian and New Zealand Clinical Trials Registry: Ref: ACTRN12612000135819, http://www.anzctr.org.au/trial_view.aspx?ID=362007.

Estimation of lean body weight in older women with hip fracture.

OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.

False-positive PCR results linked to administration of seasonal influenza vaccine.

False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen.

Recommendations for rescue of a submerged unresponsive compressed-gas diver.

The Diving Committee of the Undersea and Hyperbaric Medical Society has reviewed available evidence in relation to the medical aspects of rescuing a submerged unresponsive compressed-gas diver. The rescue process has been subdivided into three phases, and relevant questions have been addressed as follows. Phase 1, preparation for ascent: If the regulator is out of the mouth, should it be replaced? If the diver is in the tonic or clonic phase of a seizure, should the ascent be delayed until the clonic phase has subsided? Are there any special considerations for rescuing rebreather divers? Phase 2, retrieval to the surface: What is a "safe" ascent rate? If the rescuer has a decompression obligation, should they take the victim to the surface? If the regulator is in the mouth and the victim is breathing, does this change the ascent procedures? If the regulator is in the mouth, the victim is breathing, and the victim has a decompression obligation, does this change the ascent procedures? Is it necessary to hold the victim's head in a particular position? Is it necessary to press on the victim's chest to ensure exhalation? Are there any special considerations for rescuing rebreather divers? Phase 3, procedure at the surface: Is it possible to make an assessment of breathing in the water? Can effective rescue breaths be delivered in the water? What is the likelihood of persistent circulation after respiratory arrest? Does the recent advocacy for "compression-only resuscitation" suggest that rescue breaths should not be administered to a non-breathing diver? What rules should guide the relative priority of in-water rescue breaths over accessing surface support where definitive CPR can be started? A "best practice" decision tree for submerged diver rescue has been proposed.

Development and clinical validation of multiplex TaqMan® assays for rapid diagnosis of viral gastroenteritis.

There is a need to provide rapid, sensitive, and often high throughput detection of pathogens in diagnostic virology. Viral gastroenteritis is a serious health issue often leading to hospitalization in the young, the immunocompromised and the elderly. The common causes of viral gastroenteritis include rotavirus, norovirus (genogroups I and II), astrovirus, and group F adenoviruses (serotypes 40 and 41). This article describes the work-up of two internally controlled multiplex, probe-based PCR assays and reports on the clinical validation over a 3-year period, March 2007 to February 2010. Multiplex assays were developed using a combination of TaqMan™ and minor groove binder (MGB™) hydrolysis probes. The assays were validated using a panel of 137 specimens, previously positive via a nested gel-based assay. The assays had improved sensitivity for adenovirus, rotavirus, and norovirus (97.3% vs. 86.1%, 100% vs. 87.8%, and 95.1% vs. 79.5%, respectively) and also more specific for targets adenovirus, rotavirus, and norovirus (99% vs. 95.2%, 100% vs. 93.6%, and 97.9% vs. 92.3%, respectively). For the specimens tested, both assays had equal sensitivity and specificity for astrovirus (100%). Overall the probe-based assays detected 16 more positive specimens than the nested gel-based assay. Post-introduction to the routine diagnostic service, a total of 9,846 specimens were processed with multiplex 1 and 2 (7,053 pediatric, 2,793 adult) over the 3-year study period. This clinically validated, probe-based multiplex testing algorithm allows highly sensitive and timely diagnosis of the four most prominent causes of viral gastroenteritis.

Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty.

BACKGROUND: Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity. AIMS: This study aimed to investigate the effects of ageing and frailty on the safety of paracetamol in hospital inpatients commenced on short courses of the drug. METHODS: An observational cohort study of young (18-55 years, n = 19), older (≥ 70 years) fit (n = 24) and older frail (n = 28) hospital inpatients. Treatment group participants commenced regular paracetamol (3-4 g/day) during their hospital admission, whereas the control group was not exposed to paracetamol. In both groups, plasma alanine aminotransferase (ALT) was measured at baseline and day 5, and risk factors for raised ALT were recorded. A random serum paracetamol concentration was measured at day 5 in the treatment group. RESULTS: No older frail treatment participants had an abnormal day 5 ALT. Odds ratios for having a day 5 ALT above the upper limit of normal (ULN) with paracetamol use, compared with unexposed controls, were 3·7 [95% confidence intervals (CI): 0·32, 41·59] for older not frail participants and 2·5 (95% CI: 0·34, 18·3) for younger participants. Decreasing frailty score independently predicted a day 5 ALT above the ULN (P < 0·05). Day 5 serum paracetamol concentrations were highest in older frail participants (P < 0·005). CONCLUSION: Higher paracetamol concentrations observed in frail older patients after 5 days of therapeutic paracetamol do not necessarily indicate an increased risk of hepatotoxicity.

The surgical management of acute upper gastrointestinal bleeding: a 12-year experience.

INTRODUCTION: Acute upper gastrointestinal bleeding (AUGIB) is a common reason for admission to gastroenterologists, with only 2% of patients requiring surgical intervention. The aim of this study was to review the surgical management of patients with non-variceal AUGIB in a single institution over a 12-year period and compare practice with recognised regional and national standards. MATERIALS AND METHODS: Data was collected retrospectively for all patients undergoing surgery for AUGIB between September 1995 and September 2007. Audit standards included the local hospital protocol, British Society of Gastroenterology Endoscopy Committee guidelines and the UK Comparative Audit of AUGIB and the Use of Blood. RESULTS: 53 patients were identified, of which 41 case notes were available. Mean (range) age of the patients was 75.8 (45-92) years. 56% had pre-existing cardiorespiratory comorbidity and 63% were taking anti-inflammatory drugs. Pre-operative Rockall score was >or=7 in 46% and ASA score was >or=3 in 65% of patients. 56% of operations were performed by the registrar, compared with 20% reported nationally. All cases after 2004 were performed by the consultant. No operations were performed after midnight beyond 1999. 23 (56%) patients suffered post-operative complications compared with 55% reported nationally; cardiorespiratory (n = 16), wound infection (n = 7) and rebleed (n = 6). 37% required intensive care support and median length of hospital stay was 13 days. In-hospital mortality rate was 10%, compared with 30% reported nationally and this increased with rising Rockall, Blatchford, APACHE-2, P-POSSUM and Charlson scores. CONCLUSIONS: These findings highlight the high rate of morbidity and mortality associated with surgical treatment for AUGIB. The small volume of cases and reduction in registrar operating raises training issues. An integrated approach with greater use of interventional radiology is likely to play a greater role in the future.

Utility of regular medical examinations of occupational divers.

The utility of regular medical fitness-for-diving examinations of occupational divers is unknown. The aim of this audit was to investigate the impact on the employment of occupational divers of a 5-yearly medical examination and an annual health surveillance questionnaire administered in intervening years. The medical records of all New Zealand occupational divers registered with the Department of Labour for at least 5 years were audited (n= 336). Each record included at least two full medical examinations (mean spacing of 5.6 years). An impact on career was defined as the diver being issued with either a conditional certificate of fitness or being graded as temporarily or permanently unfit for diving. The means by which the relevant medical issue was identified was recorded. Ten (3%) of 336 divers had an assessment outcome, which had a career impact. One was considered permanently unfit, four were temporarily unfit, and five were issued with conditional certification. Two were identified by respiratory function testing and eight by way of their responses to the questionnaire; none was found by the medical interview and examination process. The questionnaire system did not 'miss' any divers who developed a critically important health problem, and detected most of those with less important problems. Five yearly medical examinations have a low detection rate for important health problems, but remain useful for discussion of risk understanding, acceptance and mitigation.