Scoping review of mode of anaesthesia in emergency surgery.

BACKGROUND: Emergency surgery encompasses more than 50 per cent of the surgical workload; however, research efforts are disproportionally low. The mode of anaesthesia used during emergency surgery may affect outcomes, but the extent of research and the impact of the different modes of anaesthesia used are unclear. METHODS: MEDLINE and Embase were searched using scoping review methodology with a rapid systematic search strategy, identifying any study comparing locoregional (local, nerve block, subarachnoid, epidural) anaesthesia with general anaesthesia. All studies describing outcomes of emergency surgery with differing modes of anaesthesia were identified. Excluded were: studies published before 2003, studies enrolling patients aged less than 18 years and studies using sedation only. RESULTS: Forty-two studies were identified, describing 11 surgical procedures. Most publications were retrospective cohort studies (32). A very broad range of clinical and patient-reported outcomes were described, with wide variation in the outcomes reported in different studies. CONCLUSION: Reporting of mode of anaesthesia is inconsistent across different procedures and is often absent. There is a need for directed research efforts to improve the reporting standards of anaesthesia interventions, to understand the role of different modes of anaesthesia in specific emergency surgical procedures, and to standardize outcome reporting using core outcome sets.

ANTECEDENTES: La cirugía de urgencias constituye > 50% de la carga de trabajo quirúrgico, aunque los esfuerzos realizados en investigación en este ámbito son desproporcionadamente bajos. La modalidad de anestesia utilizada durante la cirugía de urgencias puede afectar a los resultados, sin embargo, la investigación realizada y el impacto de los diferentes tipos de anestesia utilizados no están claros. MÉTODOS: Se realizaron búsquedas en Medline y Embase utilizando una metodología enfocada a la recuperación de revisiones, con una estrategia de búsqueda sistemática rápida, identificando cualquier estudio que comparara la anestesia locorregional (local, bloqueo nervioso, subaracnoidea, epidural) con la anestesia general. Se identificaron todos los estudios que describían los resultados de la cirugía de urgencias con diferentes tipos de anestesia. Se excluyeron los estudios publicados antes del 2003, los estudios que reclutaron pacientes < 18 años y los estudios que solo usaron sedación. RESULTADOS: Se identificaron 42 estudios que describían 11 procedimientos quirúrgicos. La mayoría de publicaciones fueron estudios de cohortes retrospectivos (n = 32). Se describió una gama muy amplia de resultados clínicos y resultados aportados por los pacientes, con una amplia variación en los resultados de los diferentes estudios. CONCLUSIÓN: Los resultados publicados respecto a la modalidad de anestesia empleada en diferentes procedimientos quirúrgicos son inconsistentes, a menudo esta información está ausente y no se pueden establecer conclusiones sobre el impacto del tipo de anestesia en los resultados. Es necesario realizar esfuerzos dirigidos a la investigación para mejorar la notificación de los estándares de los procedimientos de anestesia, comprender el papel de los diferentes tipos de anestesia en los procedimientos quirúrgicos específicos de urgencias, y estandarizar la presentación de los resultados obtenidos utilizando un conjunto de datos principales.

Adapting the James Lind Alliance priority setting process to better support patient participation: an example from cystic fibrosis.

PLAIN ENGLISH SUMMARY: Cystic fibrosis (CF) is the commonest life-limiting inherited disorder in the UK. It affects many parts of the body including the lungs and gut leading to increased infection and problems digesting food. People with CF need to undergo many treatments each day throughout their whole lives. These include tablets, inhalers and breathing exercises, which are a huge burden, taking up several hours every dayIt is therefore, really important that the treatments we give are supported by good evidence, usually gathered from clinical trials. Unfortunately, we do not have good evidence for many of the CF treatments. We recently ran an exercise known as a James Lind Alliance Priority Setting Partnership (JLA PSP) to find out which the CF community feel are the top priority research questions. People with CF and those who look after them suggested questions to be answered by clinical trials. Through a series of online surveys and workshops these were then shortlisted to give a final top ten.Due to infection risk people with CF are advised not to mix, this meant we had to do things differently to the usual way JLA PSPs are carried out. We used videoconferencing to enable multiple people with CF to participate. Surveys were accessible online and promoted through social media. ABSTRACT: Background The James Lind Alliance (JLA) method is well recognised for setting research priorities. The JLA approach involves a combination of surveys and workshop interactions between patients, carers and health care professionals to identify and agree on a "top ten" list of research questions. Respiratory infection is one of the hallmarks of cystic fibrosis (CF). To avoid cross infection, patients are advised not to meet face to face, preventing us following standard JLA methodology. Here we describe adaptations made during our recent JLA Priority Setting Partnership (PSP) in CF. Methods We elicited and prioritised research questions, using sequential online surveys, promoted through social media. People with CF participated in steering committee meetings and the final workshop, using videoconferencing. Alterations to workshop methodology enabled participants attending in person and those joining remotely, to contribute equally. We also altered the JLA methodology to include "lone" questions, asked by only one survey respondent. We are now working with the CF community to co-produce research projects that answer these top ten. Results There were 482 respondents, from 23 countries, who submitted 1080 questions. Increases in the number of responses occurred just after promotion on social media. Use of videoconferencing enabled participation of multiple people with CF and ensured participation from anywhere in the world, including hospital inpatients. Inclusion of lone questions resulted in one being included in our top ten. Conclusions There is no "one-size-fits-all" for patient involvement methodologies. Through altering the JLA methods to fit our patient group we achieved wide participation. We believe that methods used in our project may also be applied to future partnerships to increase participation, especially where people may be hospitalised or be unable to travel. The methodology we are developing through the JLA PSP CF2 project may be useful for other PSPs to follow.

Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts.

Human placentation displays many similarities with tumourigenesis, including rapid cell division, migration and invasion, overlapping gene expression profiles and escape from immune detection. Recent data have identified promoter methylation in the Ras association factor and adenomatous polyposis coli tumour suppressor genes as part of this process. However, the extent of tumour-associated methylation in the placenta remains unclear. Using whole genome methylation data as a starting point, we have examined this phenomenon in placental tissue. We found no evidence for methylation of the majority of common tumour suppressor genes in term placentas, but identified methylation in several genes previously described in some human tumours. Notably, promoter methylation of four independent negative regulators of Wnt signalling has now been identified in human placental tissue and purified trophoblasts. Methylation is present in baboon, but not in mouse placentas. This supports a role for elevated Wnt signalling in primate trophoblast invasiveness and placentation. Examination of invasive choriocarcinoma cell lines revealed altered methylation patterns consistent with a role of methylation change in gestational trophoblastic disease. This distinct pattern of tumour-associated methylation implicates a coordinated series of epigenetic silencing events, similar to those associated with some tumours, in the distinct features of normal human placental invasion and function.

Methylation of the adenomatous polyposis coli (APC) gene in human placenta and hypermethylation in choriocarcinoma cells.

Methylation of the human APC gene promoter is associated with several different types of cancers and has also been documented in some pre-cancerous tissues. We have examined the methylation of APC gene promoters in human placenta and choriocarcinoma cells. This revealed a general hypomethylation of the APC-1b promoter and a pattern with monoallelic methylation of the APC-1a promoter in full term placental tissue. However, there was no evidence of a parent-of-origin effect, suggesting random post zygotic origin of methylation. Increased methylation of this promoter was observed in all choriocarcinoma-derived trophoblast cell lines, suggesting a trophoblastic origin of placental APC methylation and implicating APC hypermethylation in the development of this group of gestational tumours. Our demonstration of placental methylation of the APC-1a promoter represents the first observation of monoallelic methylation of this gene in early development, and provides further support for a role of canonical Wnt signalling in placental trophoblast invasiveness. This also implicates tumour suppressor gene silencing as an integral part of normal human placental development.

Association between birth weight and adolescent systolic blood pressure in a caucasian birth cohort differs according to skin type, CRH promoter or 11beta-HSD2 genotype.

OBJECTIVE: To examine whether the inverse association between birth weight and blood pressure varies by skin pigmentation and/or related genotypes. STUDY DESIGN: 671 children from a predominantly caucasian birth cohort were followed-up to adolescence (mean (SD) age 14.4 (0.64)). METHODS: Data on birth weight, socioeconomic status, maternal antenatal smoking, adolescent blood pressure and polymorphisms of candidate genes were obtained and analysed by multiple linear regression. RESULTS: An increase in birth weight of 1 kg was associated with an non-significant difference in adolescent systolic blood pressure of -0.53 mm Hg (95% CI -1.72 to 0.66) per kg after adjustment for child age and cohort entry criteria. The inverse association between birth weight and systolic blood pressure was stronger for those with darker skin (> or =2% melanin) (difference in effect, p = 0.02), those with more copies of the C allele of corticotropin-releasing hormone (CRH) +T1273C (p = 0.06), and those with more copies of the short (< or =236 bp) form of the 11beta-HSD2{CA}n(repeat) microsatellite (p = 0.03). CONCLUSIONS: These findings add to the evidence that cortisol-related pathways may account for at least part of the observed birth weight-blood pressure associations.

External validation of established risk adjustment models for procedural complications after percutaneous coronary intervention.

BACKGROUND: Workable risk models for patients undergoing percutaneous coronary intervention (PCI) are needed urgently. OBJECTIVE: To validate two proposed risk adjustment models (Mayo Clinic Risk Score (MC), USA and North West Quality Improvement Programme (NWQIP), UK models) for in-hospital PCI complications on an independent dataset of relatively high risk patients undergoing PCI. SETTING: Tertiary centre in northern England. METHODS: Between September 2002 and August 2006, 5034 consecutive PCI procedures (validation set) were performed on a patient group characterised by a high incidence of acute myocardial infarction (MI; 16.1%) and cardiogenic shock (1.7%). Two external models-the NWQIP model and the MC model-were externally validated. MAIN OUTCOME MEASURE: Major adverse cardiovascular and cerebrovascular events: in-hospital mortality, Q-wave MI, emergency coronary artery bypass grafting and cerebrovascular accidents. RESULTS: An overall in-hospital complication rate of 2% was observed. Multivariate regression analysis identified risk factors for in-hospital complications that were similar to the risk factors identified by the two external models. When fitted to the dataset, both external models had an area under the receiver operating characteristic curve >or=0.85 (c index (95% CI), NWQIP 0.86 (0.82 to 0.9); MC 0.87(0.84 to 0.9)), indicating overall excellent model discrimination and calibration (Hosmer-Lemeshow test, p>0.05). The NWQIP model was accurate in predicting in-hospital complications in different patient subgroups. CONCLUSIONS: Both models were externally validated. Both predictive models yield comparable results that provide excellent model discrimination and calibration when applied to patient groups in a different geographic population other than that in which the original model was developed.

Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life.

BACKGROUND: Low birth weight is related to increased risk of coronary heart disease in adults and recently has been associated with vascular endothelial dysfunction in children. We investigated whether the relation between birth weight and endothelial function was still present in early adult life and whether there was an interaction with emerging risk factors. METHODS AND RESULTS: In 315 adults (165 women, 150 men, aged 20 to 28 years), high-resolution ultrasound was used to determine endothelium-dependent and -independent vascular responses of the brachial artery. Vascular measures were related to classic risk factors (smoking history, lipid profile, blood pressure, fasting insulin, exercise capacity, body mass index, and combined risk score) and birth weight. Low birth weight was associated with reduced flow-mediated dilation (coefficient=0.18 kg(-1), 95% CI 0.004 to 0.35, P:=0.04) but not with endothelium-independent dilation. The difference in flow-mediated dilation between the top and bottom fifths of birth weight was the same as between smokers and nonsmokers. Increasing levels of acquired risk factors overwhelmed the association, and there was a significant interaction of risk score with the birth weight-endothelial function relation (coefficient of interaction term [birth weightxrisk score] = -0.12, 95% CI -0.22 to -0.03, P:=0.01). CONCLUSIONS: Low birth weight is associated with endothelial dysfunction in young adults. This is most marked in individuals with lower risk factor profiles and may be relevant to the pathogenesis of atherosclerosis in later life.

Clinical safety of iron-fortified formulas.

BACKGROUND: Iron-fortified formulas are recommended throughout infancy and are frequently used beyond, yet safety aspects have been inadequately studied. Iron could theoretically increase pro-oxidant stress, with potential adverse effects, including infection risk, and some clinicians suspect that iron-fortified formulas induce gastrointestinal disturbance. OBJECTIVE: A planned component of a large intervention trial has been to test the hypothesis that infants receiving iron-fortified formula do not have a higher incidence of infections (primary outcome) or gastrointestinal problems (secondary outcome) than infants on low iron-formulas or cow's milk. Methods. Children (n = 493) 9 months old receiving cow's milk were recruited in 3 UK centers and randomized to: 1) cow's milk as before, 2) formula containing.9 mg/L of iron, or 3) an otherwise identical formula but containing 12 mg/L of iron. Children were followed at 3 monthly intervals and the episodes of infections, diarrhea and constipation, and general morbidity to 18 months old were recorded. Hematologic indices of iron status were determined at 18 months old. RESULTS: Serum ferritin concentrations were increased in infants receiving iron-fortified formula but there were no intergroup differences in incidence of infection, gastrointestinal problems, or in general morbidity or weight gain. CONCLUSIONS: We were unable to identify adverse health effects in older infants and toddlers consuming a high iron-containing formula (12 mg/L) even when used in populations with a low incidence of iron deficiency.

Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial.

AIMS: Iron deficiency anaemia is associated, in observational studies, with developmental disadvantage. This study tested the hypothesis that feeding iron supplemented formula from 9 to 18 months of age would improve developmental performance. SUBJECTS AND METHODS: 493 healthy children aged 9 months being fed pasteurised cows' milk were recruited from three UK centres. They were randomised to: cows' milk as before, formula containing 0.9 mg/litre iron, or formula containing 1.2 mg/litre iron, until 18 months of age. Bayley mental and psychomotor developmental indices were measured at 18 months, as were growth and haematological indices. RESULTS: Children fed iron fortified formula had higher plasma ferritin concentrations, but there were no significant intergroup differences in development or growth. CONCLUSIONS: There are no developmental or growth advantages in children given iron supplemented formula, but a benefit for a minority who were anaemic, or the possibility that a benefit may emerge at a later age, cannot be excluded.

Diabetic cystopathy presenting as primary acute urinary retention in a previously undiagnosed young male diabetic patient.

Lower genito-urinary problems are part of the polyneuropathy of diabetes. Cystopathy affects 40%-85% of diabetic patients, although less than half are symptomatic. We report on a 42-year-old patient who was not known to be diabetic, and who presented to the urologists with primary acute urinary retention. His underlaying disease was detected by a test for random blood glucose. More common causes were excluded with careful clinical and radiological examinations. He was managed with insulin and self-catheterization. Diabetes should be considered as a differential diagnosis in relatively young men who present with unexplained acute urinary retention.

Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions.

BACKGROUND: Aluminum, a contaminant of commercial intravenous-feeding solutions, is potentially neurotoxic. We investigated the effect of perinatal exposure to intravenous aluminum on the neurologic development of infants born prematurely. METHODS: We randomly assigned 227 premature infants with gestational ages of less than 34 weeks and birth weights of less than 1850 g who required intravenous feeding before they could begin enteral feeding to receive either standard or specially constituted, aluminum-depleted intravenous-feeding solutions. The neurologic development of the 182 surviving infants who could be tested was assessed by using the Bayley Scales of Infant Development at 18 months of age. RESULTS: The 90 infants who received the standard feeding solutions had a mean (+/-SD) Bayley Mental Development Index of 95+/-22, as compared with 98+/-20 for the 92 infants who received the aluminum-depleted solutions (P=0.39). In a planned subgroup analysis of infants in whom the duration of intravenous feeding exceeded the median and who did not have neuromotor impairment, the mean values for the Bayley Mental Development Index for the 39 infants who received the standard solutions and the 41 infants who received the aluminum-depleted solutions were 92+/-20 and 102+/-17, respectively (P=0.02). The former were significantly more likely (39 percent, vs. 17 percent of the latter group; P=0.03) to have a Mental Development Index of less than 85, increasing their risk of subsequent educational problems. For all 157 infants without neuromotor impairment, increasing aluminum exposure was associated with a reduction in the Mental Development Index (P=0.03), with an adjusted loss of one point per day of intravenous feeding for infants receiving the standard solutions. CONCLUSIONS: In preterm infants, prolonged intravenous feeding with solutions containing aluminum is associated with impaired neurologic development.

Maternal smoking and blood pressure in 7.5 to 8 year old offspring.

Reduced fetal growth in babies born preterm may be associated with reduced later blood pressure, but in children born at term, higher blood pressure. It was hypothesised, therefore, that maternal smoking in pregnancy, associated with reduced fetal growth, programmes later blood pressure differentially according to length of gestation. Six hundred and eighteen children born preterm and now aged 7.5 to 8 years were studied prospectively. Systolic blood pressure in children from smoking compared with non-smoking mothers was significantly lower in those born before 33 weeks' gestation and significantly higher in those born at 33 or more weeks. Within the range 0-40 cigarettes per day until delivery (after adjusting for potentially confounding factors, including social class and current weight) each 10 was associated with a 1.5 mm Hg fall and 2.9 mm Hg rise in pressure for children born below or above 33 weeks' gestation respectively. Similar though smaller differences were seen in diastolic pressure. These data support our hypothesis that later effects of insults impairing fetal growth are gestation dependent, and provide the first evidence that maternal smoking may have long term consequences for blood pressure in children.

Flexible cystoscopy in men: is topical anaesthesia with lignocaine gel worthwhile?

OBJECTIVE: The value of 2% lignocaine gel as a topical anaesthetic for flexible cystoscopy in men was tested in a prospective, randomized, double-blind, placebo controlled trial. PATIENTS AND METHODS: A total of 138 patients were entered into the study. Group A patients (n = 75) received 10 ml of 2% lignocaine gel intraurethrally whilst 10 ml of plain lubricating gel was instilled in the remaining 63 patients (Group B). Patient discomfort was recorded by means of a four-point descriptive pain scale (completed by both surgeon and patient) and a 100 mm non-graphic rating visual analogue scale (patient only). RESULTS: The results showed no significant difference between the two treatments irrespective of the method of recording. CONCLUSION: This study shows that 2% lignocaine gel offers no advantage over plain lubricating gel in providing analgesia for flexible cystoscopy. In this situation good lubrication may be a more important factor than topical anaesthesia.

Food and drug reactions, wheezing, and eczema in preterm infants.

Allergic reactions were investigated in 777 preterm infants who were randomly assigned to early diet and followed up to 18 months post term. Wheezing or asthma was common (incidence 23%); it was associated with neonatal ventilation, maternal smoking, and a family history of atopy and was unexpectedly reduced in babies born by caesarean section. Even in non-ventilated infants, the incidence of subsequent wheezing was 18%, rising to an estimated 44% (using logistic regression) when the foregoing risk factors (excluding ventilation) were present. Eczema occurred in 151 infants (19%) and was strongly associated with multiple pregnancy (30% incidence in twins or triplets). Reactions to cows' milk (incidence: 4.4% from detailed history; 0.8% confirmed by challenge), other foods (10%), and drugs (5%) were within the range reported in full term infants. Milk and food reactions were associated with multiple pregnancy (19%) and a family history of atopy. Reactions to drugs were least likely to occur in infants who had been ventilated and were on multiple medications in the neonatal period, suggesting that drug tolerance may have developed. We speculate that preterm infants may be a high risk group for asthma and eczema, which could imply an association between atopy and prematurity.

Genetics of the rat CT system: its apparent complexity is a consequence of cross-reactivity between the distinct MHC class I antigens RT1.C and RT1.A.

The rat CT antigens are a system of medial histocompatibility antigens linked to RT1, the rat major histocompatibility complex (MHC). They have aroused interest firstly because, despite their extreme serological weakness, they are targets for 'unrestricted' cytotoxic T lymphocytes (CTL); and secondly because they have appeared to represent a complex genetic system in terms both of the number of genetic loci involved and the number of distinguishable antigenic specificities expressed. The CT system was originally defined by the reactions of LEW anti-F344 (RT1l anti-RT1lv1) secondary in vitro CTL. These CTL reacted strongly on DA(RT1av1) targets, but much more weakly on AUG or PVG (RT1c) targets. We have used the recently derived RT1 recombinant rat strains PVG.R19 (RT1.Aav1Iav1Cc) and PVG.R20 (RT1.AcIcCav1) to investigate the genetic control of this system. Contrary to previous interpretations, the results are consistent with a model in which CT is a single locus, which maps to the RT1.C region. In addition, our results demonstrate that there is cross-reactivity of anti-RT1C CTLs on RT1A products, and we suggest that the earlier placement of a CT locus in the RT1.A region was probably incorrect and a consequence of this cross-reactivity.