Efficacy of Topical Vancomycin- and Gentamicin-Loaded Calcium Sulfate Beads or Systemic Antibiotics in Eradicating Polymicrobial Biofilms Isolated from Diabetic Foot Infections within an In Vitro Wound Model.

Diabetic foot ulcers are notoriously difficult to heal, with ulcers often becoming chronic, in many cases leading to amputation despite weeks or months of antibiotic therapy in addition to debridement and offloading. Alternative wound biofilm management options, such as topical rather than systemic delivery of antimicrobials, have been investigated by clinicians in order to improve treatment outcomes. Here, we collected blood and tissue from six subjects with diabetic foot infections, measured the concentrations of antibiotics in the samples after treatment, and compared the microbiota within the tissue before treatment and after 7 days of antibiotic therapy. We used an in vitro model of polymicrobial biofilm infection inoculated with isolates from the tissue we collected to simulate different methods of antibiotic administration by simulated systemic therapy or topical release from calcium sulfate beads. We saw no difference in biofilm bioburden in the models after simulated systemic therapy (representative of antibiotics used in the clinic), but we did see reductions in bioburden of between 5 and 8 logs in five of the six biofilms that we tested with topical release of antibiotics via calcium sulfate beads. Yeast is insensitive to antibiotics and was a component of the sixth biofilm. These data support further studies of the topical release of antibiotics from calcium sulfate beads in diabetic foot infections to combat the aggregate issues of infectious organisms taking the biofilm mode of growth, compromised immune involvement, and poor systemic delivery of antibiotics via the bloodstream to the site of infection in patients with diabetes.

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.

Top research priorities in healthcare-associated infection in the UK.

BACKGROUND: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. AIM: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. METHODS: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. FINDINGS: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. CONCLUSIONS: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties.

Skeletal deformities associated with nutritional congenital rickets in newborn lambs.

CASE HISTORY: A group of 545 pregnant rising 2-year-old Coopdale ewes on a Southland sheep farm were grazed over winter on a fodder beet (Beta vulgaris) crop. Subsequently, 45 out of approximately 750 lambs were born with a variety of skeletal deformities, including shortened limbs, varus and valgus angular limb deformities, palmar grade stance and cranial bowing of the carpus. Analysis of the crop showed the fodder beet contained a low percentage of phosphorus. In addition, 60 out of 460 rising 2-year-old ewes that had been grazed on the fodder beet crop as 1-year-olds had incisor abnormalities and malocclusion. PATHOLOGICAL FINDINGS: Two affected lambs (1-day-old and 3-days-old) with representative clinical signs examined postmortem were found to have markedly enlarged costochondral junctions, and noticeably enlarged long bone metaphyses. In addition, one lamb had a dense band of metaphyseal sclerosis beneath the physes of all long bones examined. Histopathological findings included small islands and columns of chondrocytes and eosinophilic cartilage matrix present in the metaphysis. Metaphyseal trabeculae were disorganised and often lined by accumulations of pale pink osteoid; similar pale pink osteoid was also present in the cortices. Unerupted molar teeth in the affected lambs lacked a layer of enamel, and the dentine was irregular with globular basophilia. DIAGNOSIS: The gross and histopathological lesions were consistent with a diagnosis of rickets. CLINICAL RELEVANCE: Nutritional congenital rickets has not been previously diagnosed in sheep, but is a recognised disease of human infants with vitamin D deficient mothers. The rickets in affected lambs was most likely associated with phosphorus deficiency as a result of the pregnant ewes grazing fodder beet during gestation. While vitamin D deficiency was not definitively ruled out in these cases, practitioners are alerted to the possible effects of feeding phosphorus-deficient fodder beet to ewes for long periods during gestation and to 1-year-old sheep during important growth periods.

The SSTARS (STeroids and Stents Against Re-Stenosis) Trial: Different stent alloys and the use of peri-procedural oral corticosteroids to prevent in-segment restenosis after percutaneous coronary intervention.

BACKGROUND: Stent design and technological modifications to allow for anti-proliferative drug elution influence restenosis rates following percutaneous coronary intervention (PCI). We aimed to investigate whether peri-procedural administration of corticosteroids or the use of thinner strut cobalt alloy stents would reduce rates of binary angiographic restenosis (BAR) after PCI. METHODS: This was a two centre, mixed single and double blinded, randomised controlled trial using a factorial design. We compared (a) the use of prednisolone to placebo, starting at least six hours pre-PCI and continued for 28days post-PCI, and (b) cobalt chromium (CoCr) to stainless steel (SS) alloy stents, in patients admitted for PCI. The primary end-point was BAR at six months. RESULTS: 315 patients (359 lesions) were randomly assigned to either placebo (n=145) or prednisolone (n=170) and SS (n=160) or CoCr (n=160). The majority (58%) presented with an ACS, 11% had diabetes and 287 (91%) completed angiographic follow up. BAR occurred in 26 cases in the placebo group (19.7%) versus 31 cases in the prednisolone group (20.0%) respectively, p=1.00. For the comparison between SS and CoCr stents, BAR occurred in 32 patients (21.6%) versus 25 patients (18.0%) respectively, p=0.46. CONCLUSION: Our study showed that treating patients with a moderately high dose of prednisolone for 28days following PCI with BMS did not reduce the incidence of BAR. In addition, we showed no significant reduction in 6month restenosis rates with stents composed of CoCr alloy compared to SS (http://www.isrctn.com/ISRCTN05886349).

The effect of known cardiovascular risk factors on carotid-femoral pulse wave velocity in school-aged children: a population based twin study.

Childhood cardiovascular risk factors affect vascular function long before overt cardiovascular disease. Twin studies provide a unique opportunity to examine the influence of shared genetic and environmental influences on childhood cardiovascular function. We examined the relationship between birth parameters, markers of adiposity, insulin resistance, lipid profile and blood pressure and carotid-femoral pulse wave velocity (PWV), a validated non-invasive measure of arterial stiffness in a healthy cohort of school-aged twin children. PWV was performed on a population-based birth cohort of 147 twin pairs aged 7-11 years. Fasting blood samples, blood pressure and adiposity measures were collected concurrently. Mixed linear regression models were used to account for twin clustering, within- and between-twin pair associations. There were positive associations between both markers of higher adiposity, insulin resistance, elevated triglycerides and PWV, which remained significant after accounting for twin birth-set clustering. There was a positive association between both diastolic and mean arterial blood pressure and PWV in within-pair analysis in dizygotic, but not monozygotic twins, indicating genetic differences evident in dizygotic not monozygotic twins may affect these associations. Increased blood pressure, triglycerides and other metabolic markers are associated with increased PWV in school-aged twins. These results support both the genetic and environmental contribution to higher PWV, as a marker of arterial stiffness, and reiterate the importance of preventing metabolic syndrome from childhood.

Variance estimation for stratified propensity score estimators.

Propensity score methods are increasingly used to estimate the effect of a treatment or exposure on an outcome in non-randomised studies. We focus on one such method, stratification on the propensity score, comparing it with the method of inverse-probability weighting by the propensity score. The propensity score--the conditional probability of receiving the treatment given observed covariates--is usually an unknown probability estimated from the data. Estimators for the variance of treatment effect estimates typically used in practice, however, do not take into account that the propensity score itself has been estimated from the data. By deriving the asymptotic marginal variance of the stratified estimate of treatment effect, correctly taking into account the estimation of the propensity score, we show that routinely used variance estimators are likely to produce confidence intervals that are too conservative when the propensity score model includes variables that predict (cause) the outcome, but only weakly predict the treatment. In contrast, a comparison with the analogous marginal variance for the inverse probability weighted (IPW) estimator shows that routinely used variance estimators for the IPW estimator are likely to produce confidence intervals that are almost always too conservative. Because exact calculation of the asymptotic marginal variance is likely to be complex, particularly for the stratified estimator, we suggest that bootstrap estimates of variance should be used in practice.

Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression.

Cohort studies have considerable prima facie value for investigating epigenetic processes in psychological disorder; however, the future prospects for such studies will depend on valid peripheral markers. The purpose of this pilot study was to investigate association between buccal cell methylation and risk for depression. Epigenotyping was limited to promoter methylation of the serotonin transporter gene (5HTT). A transcription limiting VNTR in the 5HTT promoter (5HTTLPR) was also genotyped. A nested sample of 25 depressed and 125 non-depressed adolescents was drawn from an established longitudinal study of adolescent health. There was no association between depressive symptoms and either buccal cell 5HTT methylation or 5HTTLPR. However, depressive symptoms were more common among those with elevated buccal cell 5HTT methylation who carried 5HTTLPR short-allele (OR 4.9, CI 1.9-13, p=0.001). Both complete and partial (as little as 10%) methylation of a 5HTT reporter gene in an expressing cell line reduced 5HTT activity. Replication is needed.

Primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: changing patterns of vascular access, radial versus femoral artery.

OBJECTIVE: To examine the safety and efficacy of emergency transradial primary percutaneous coronary intervention for ST-elevation myocardial infarction. DESIGN: Single-centre observational study with prospective data collection. SETTING: A regional cardiac centre, United Kingdom. PATIENTS: 1051 consecutive patients admitted with ST-elevation myocardial infarction, without cardiogenic shock, between November 2004 and October 2008. INTERVENTIONS: Percutaneous coronary interventions by radial and femoral access MAIN OUTCOME MEASURES: The primary outcome measures were procedural success, major vascular complication and failed initial access strategy. Secondary outcomes were in-hospital mortality and major adverse cardiac and cerebrovascular events, needle-to-balloon times, contrast volume used, radiation dose absorbed and time to discharge. Multiple regression analysis was used to adjust for potential differences between the groups. RESULTS: 571 patients underwent radial access and 480 femoral. A variable preference for radial access was observed among the lead operators (between 21% and 90%). Procedural success was similar between the radial and femoral groups, but major vascular complications were more frequent at the site of femoral access (0% radial versus 1.9% femoral, p = 0.001). Failure of the initial access strategy was more frequent in the radial group (7.7% versus 0.6%, p<0.001). Adjustment for other procedural and clinical predictors did not alter these findings. Needle-to-balloon time, as a measure of procedural efficiency, was equal for radial and femoral groups. CONCLUSIONS: In the setting of acute ST-elevation myocardial infarction without cardiogenic shock, transradial primary angioplasty is safe, with comparable outcomes to a femoral approach and a lower risk of vascular complications.

Reduced membrane bound CD14 expression in the cord blood of infants with a family history of allergic disease.

BACKGROUND: Infants at increased risk of allergic disease have altered immune function at birth, but the specific immune changes described differ between studies and their precise nature is not well defined. Changes affecting innate immune responses may be particularly important in allergic disease pathogenesis. OBJECTIVE: We investigated whether inherited risk of allergic disease is associated with altered markers of innate immunity, T cell regulation or dendritic cell (DC) percentage in human newborns. METHODS: Cord blood was collected from infants at low risk (no parent affected by allergic disease, n=14), intermediate risk (one affected parent, n=54) or high risk (two affected parents, n=25) of developing allergic disease. Cord blood mononuclear cells were cultured with ovalbumin (OVA), lipopolysaccharide, lipoteichoic acid (LTA), heat-killed lactobacillus, alpha-CD3 or medium alone. Cells were analysed by flow cytometry for expression of CD14, FoxP3 and DC percentage, and by real-time RT-PCR for TLR2 and TLR4 expression in infants at intermediate or high risk of allergic disease. RESULTS: Infants at high risk of allergic disease had reduced percentage of CD14(+) monocytes (P=0.01) and reduced CD14 mean fluorescence intensity (P=0.01) in uncultured mononuclear cells. They also had decreased DC percentage in mononuclear cells cultured with OVA (P=0.04), lipopolysaccharide (P=0.01), LTA (P=0.02) and alpha-CD3 (P=0.03) as compared with infants at intermediate or low risk of allergic disease. No relationship was seen between risk of allergic disease and TLR2 or TLR4 expression, or FoxP3 expression in cultured cells. CONCLUSIONS: Infants with a biparental history of allergic disease have altered markers of innate immunity at birth, with reduced expression of membrane bound CD14 and consequently reduced in vitro development of DCs. Further work is needed to understand the role that these alterations play in the pathogenesis of allergic disease, and whether interventions to up-regulate fetal CD14 expression can prevent allergic disease.

Maternal 25-hydroxyvitamin D concentration and offspring birth size: effect modification by infant VDR genotype.

BACKGROUND/OBJECTIVES: We tested the hypothesis that the relationship between maternal 25-hydroxyvitamin D (25-(OH)D) and offspring birth size differs according to offspring vitamin D receptor (VDR) genotype (Apa1, Bsm1, Fok1 or Taq1). SUBJECTS/METHODS: Mothers of 354 singleton babies had serum 25-(OH)D concentration measured at 28-30 weeks of gestation and consented to measurement of their babies soon after birth. DNA was extracted from the babies' Guthrie cards. RESULTS: There was evidence of effect modification by infant FokI genotype. Babies of deficient mothers had lower birth weight with FF or Ff, but not ff genotype (P-value for interaction after adjustment for potential confounding factors=0.02), but thicker subscapular and suprailiac skinfolds with ff, but not FF or Ff genotype (P=0.008 and 0.02, respectively). Sample size was insufficient to investigate effect modification by the other VDR polymorphisms. CONCLUSIONS: These preliminary findings suggest that studies of maternal vitamin D status and birth size may need to take VDR genotype into account.

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.

Hopping hotspots: global shifts in marine biodiversity.

Hotspots of high species diversity are a prominent feature of modern global biodiversity patterns. Fossil and molecular evidence is starting to reveal the history of these hotspots. There have been at least three marine biodiversity hotspots during the past 50 million years. They have moved across almost half the globe, with their timing and locations coinciding with major tectonic events. The birth and death of successive hotspots highlights the link between environmental change and biodiversity patterns. The antiquity of the taxa in the modern Indo-Australian Archipelago hotspot emphasizes the role of pre-Pleistocene events in shaping modern diversity patterns.

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.

Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth.

AIM: A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. DESIGN: We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. RESULTS: In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0; P=0.02). Protein intake was also associated negatively with ponderal index (beta=-0.01; 95% CI: -0.02, -0.00; P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. CONCLUSIONS: This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.