How common are vascular injuries in open tibial fractures? A prospective longitudinal cohort study.

BACKGROUND: Tibial fractures have an incidence of 15% of all adult fractures. They have been shown to have the highest incidence of non-union in long bone fractures and the highest incidence of vascular injury. Evidence from the literature suggests that a good vascular supply is important to ensure bone union. The aim of our study was to prospectively assess the incidence of vascular injuries in open tibial fractures and determine whether they were associated with an increased risk of non-union. METHODS: We performed a prospective study to investigate the incidence of arterial injuries with computed tomography angiography (CTA) in patients with Gustilo-Anderson grade I-III open tibial fractures between 2013 and 2015. CTA was performed with the trauma series at acute admission and reported by two independent musculoskeletal radiologists. Patients were followed up with clinical and radiographic assessment for 1 year. RESULTS: We recruited 77 patients into the study, and 56 patients (47 males, 9 females) were available for the final analysis, between 16 and 90 years of age. At the initial assessment, 29% had signs of arterial injury with active extravasation in 5%. The most common site of injury was in the diaphysis (87.5%), and the commonest mechanism was a road traffic accident. We found no significant relation between occult vascular injury and non-union (p > 0.05). CONCLUSION: The incidence of vascular injury in open tibial fractures is 29%, and CTA is therefore a useful test in identifying vascular injuries that may require vascular intervention.

Comparative analysis of the outcomes of elective abdominal aortic aneurysm repair in England and Sweden.

BACKGROUND: There is substantial international variation in mortality after abdominal aortic aneurysm (AAA) repair; many non-operative factors influence risk-adjusted outcomes. This study compared 90-day and 5-year mortality for patients undergoing elective AAA repair in England and Sweden. METHODS: Patients were identified from English Hospital Episode Statistics and the Swedish Vascular Registry between 2003 and 2012. Ninety-day mortality and 5-year survival were compared after adjustment for age and sex. Separate within-country analyses were performed to examine the impact of co-morbidity, hospital teaching status and hospital annual caseload. RESULTS: The study included 36 249 patients who had AAA treatment in England, with a median age of 74 (i.q.r. 69-79) years, of whom 87·2 per cent were men. There were 7806 patients treated for AAA in Sweden, with a median of age 73 (68-78) years, of whom 82·9 per cent were men. Ninety-day mortality rates were poorer in England than in Sweden (5·0 versus 3·9 per cent respectively; P < 0·001), but were not significantly different after 2007. Five-year survival was poorer in England (70·5 versus 72·8 per cent; P < 0·001). Use of EVAR was initially lower in England, but surpassed that in Sweden after 2010. In both countries, poor outcome was associated with increased age. In England, institutions with higher operative annual volume had lower mortality rates. CONCLUSION: Mortality for elective AAA repair was initially poorer in England than Sweden, but improved over time alongside greater uptake of EVAR, and now there is no difference. Centres performing a greater proportion of EVAR procedures achieved better results in England.

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea.

In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA-induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA-specific interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-5, IL-6, IL-10 and IL-13 responses, and lower dPly-IL-6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA-IL-5 and PspA-IL-13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly-IL-6 responses with a higher frequency of cord antigen-presenting cells. In the PNG cohort, higher PspA-specific IL-5 and IL-6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA-IL-10 CBMC responses. Pneumococcus-specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

Childhood atopy and mental health: a prospective, longitudinal investigation.

BACKGROUND: Prior studies have suggested a relationship between atopy and mental health, although methodological barriers have limited the generalizability of these findings. The objective of this study was to investigate the relationship between early-life atopy and vulnerability to mental health problems among youth in the community. METHOD: Data were drawn from the Raine Study (N = 2868), a population-based birth cohort study in Western Australia. Logistic regression and generalized estimating equations were used to examine the relationship between atopy at ages 1-5 years [using parent report and objective biological confirmation (sera IgE)], and the range of internalizing and externalizing mental health problems at ages 5-17 years. RESULTS: Atopy appears to be associated with increased vulnerability to affective and anxiety problems, compared to youth without atopy. These associations remained significant after adjusting for a range of potential confounders. No relationship was evident between atopy and attention deficit hyperactivity disorder or externalizing problems. CONCLUSIONS: Findings are the first linking atopy (measured by both parent report and objective verification) with increased vulnerability to affective and anxiety problems. Therefore, replication is required. If replicated, future research aimed at understanding the possible biological and/or social and environmental pathways underlying these links is needed. Such information could shed light on shared pathways that could lead to more effective treatments for both atopy and internalizing mental health problems.

Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery.

BACKGROUND: The incidence and impact of postoperative complications are poorly described. Failure-to-rescue, the rate of death following complications, is an important quality measure for perioperative care but has not been investigated across multiple health care systems. METHODS: We analysed data collected during the International Surgical Outcomes Study, an international 7-day cohort study of adults undergoing elective inpatient surgery. Hospitals were ranked by quintiles according to surgical procedural volume (Q1 lowest to Q5 highest). For each quintile we assessed in-hospital complications rates, mortality, and failure-to-rescue. We repeated this analysis ranking hospitals by risk-adjusted complication rates (Q1 lowest to Q5 highest). RESULTS: A total of 44 814 patients from 474 hospitals in 27 low-, middle-, and high-income countries were available for analysis. Of these, 7508 (17%) developed one or more postoperative complication, with 207 deaths in hospital (0.5%), giving an overall failure-to-rescue rate of 2.8%. When hospitals were ranked in quintiles by procedural volume, we identified a three-fold variation in mortality (Q1: 0.6% vs Q5: 0.2%) and a two-fold variation in failure-to-rescue (Q1: 3.6% vs Q5: 1.7%). Ranking hospitals in quintiles by risk-adjusted complication rate further confirmed the presence of important variations in failure-to-rescue, indicating differences between hospitals in the risk of death among patients after they develop complications. CONCLUSIONS: Comparison of failure-to-rescue rates across health care systems suggests the presence of preventable postoperative deaths. Using such metrics, developing nations could benefit from a data-driven approach to quality improvement, which has proved effective in high-income countries.

Quality of life, symptoms and treatment satisfaction in patients with aortic aneurysm using new abdominal aortic aneurysm-specific patient-reported outcome measures.

BACKGROUND: The aim of this study was to present preliminary data on quality of life (QoL), symptoms and treatment satisfaction gathered using three new abdominal aortic aneurysm (AAA)-specific patient-reported outcome measures (PROMs). METHODS: Patients with AAA were recruited from five National Health Service Trusts to complete the three new PROMs: the AneurysmDQoL, AneurysmSRQ and AneurysmTSQ. Patients were either under surveillance or had undergone AAA repair (open or endovascular) during the preceding 24 months. Data were initially collected as part of a study assessing the psychometric properties of the new measures, before being used in the observational analysis of outcomes presented here. RESULTS: Results, although largely non-significant, showed interesting trends. The impact of AAA repair on QoL appeared to worsen progressively after open repair (OR) and improve progressively after endovascular aneurysm repair (EVAR). Conversely, symptoms seemed to become progressively worse after EVAR and progressively better after OR. Information and understanding were key sources of dissatisfaction before the intervention, whereas postoperative dissatisfaction was related to bother from symptoms, follow-up and feedback about scan results. CONCLUSION: Although a larger, prospective data set is necessary to explore outcomes more fully with the new AAA-specific PROMs, the observational data presented here suggest there may be clinically important differences in the symptoms, impact on QoL and treatment satisfaction associated with OR and EVAR.

Preoperative morphology influences thoracic aortic aneurysm sac expansion after endovascular repair.

BACKGROUND: The fate of the aneurysm sac after thoracic endovascular aortic repair (TEVAR) remains poorly defined. The aim of this study was to characterize the incidence of aneurysm sac expansion after TEVAR, and to determine the effect of aneurysm morphology on postoperative sac behaviour. METHODS: Preoperative and postoperative CT angiography (CTA) images were analysed from a proprietary database (M2S). TEVARs undertaken for thoracic aortic aneurysms from 2004 to 2013 were included. Preoperative aortic morphology was available for each patient. Post-TEVAR sac expansion was defined as an increase in aortic diameter of at least 5 mm. The influence of aortic morphological variables on sac expansion was assessed using Cox regression and Kaplan-Meier analysis. RESULTS: CTA images were available for 899 patients who underwent TEVAR. Median follow-up was 2·1 (i.q.r. 1·7-2·4) years. Some 46·0 per cent had a maximum aneurysm diameter of 55 mm or more at the time of repair. The 5-year rate of freedom from sac expansion of at least 5 mm was 60·9 per cent. The sac expansion rate after 3 years was higher when the proximal sealing zone was over 38 mm in diameter (freedom from expansion 51·2 per cent versus 76·6 per cent for diameter 38 mm or less; P < 0·001), or 20 mm or less in length (freedom from expansion 67·3 per cent versus 77·1 per cent for length exceeding 20 mm; P = 0·022). Findings for the distal sealing zone were similar. The risk of sac expansion increased according to the number of adverse morphological risk factors (freedom from expansion rate 79·1 per cent at 3 years in patients with 2 or fewer risk factors versus 45·7 per cent in those with more than 2; P < 0·001). CONCLUSION: Sac expansion was common in this cohort of patients undergoing TEVAR for thoracic aortic aneurysm. Aneurysm sac expansion was significantly influenced by adverse morphological features in the aortic stent-graft sealing zones.

Design of new patient-reported outcome measures to assess quality of life, symptoms and treatment satisfaction in patients with abdominal aortic aneurysm.

BACKGROUND: No condition-specific patient-reported outcome measures exist for patients with abdominal aortic aneurysm (AAA). The aim of this work was to develop three questionnaires to assess quality of life (QoL), symptoms and treatment satisfaction in patients with AAA. METHODS: Semistructured interview techniques were used to explore patients' experiences of having an AAA in a series of focus groups and in-depth interviews. The information gathered was used to inform design and selection of items for the new tools; the overall structure of the new questionnaires was based on tools developed previously for patients with diabetes and other conditions. RESULTS: Fifty-four patients (51 men, 3 women; mean age 71·9 years) were recruited from four NHS Trusts to participate in focus groups or interviews, either while under surveillance, or following AAA repair (using open or endovascular techniques). The Aneurysm-Dependent Quality of Life Questionnaire (AneurysmDQoL) is an individualized measure of the impact of AAA on patients' QoL. Twenty-three domains were chosen specifically for their relevance to patients with AAA, with a further two overview items to assess overall QoL and the impact of AAA on QoL. The Aneurysm Symptom Rating Questionnaire (AneurysmSRQ) is a 44-item measure assessing physical and psychological symptoms reported by patients with AAA. The Aneurysm Treatment Satisfaction Questionnaire (AneurysmTSQ) contains 11 items, suitable for patients before and after surgical intervention. CONCLUSION: The iterative development process reported here has confirmed that these three new tools have good face and content validity for patients with AAA.

Expansion rate of descending thoracic aortic aneurysms.

BACKGROUND: Surveillance is mandatory for all patients with a thoracic aortic aneurysm (TAA). The frequency of surveillance imaging, however, is not evidence-based, as few data exist regarding TAA growth rates. This study aimed to determine the rate of TAA expansion and to inform surveillance intervals based on TAA diameter. METHODS: Patients with a TAA for whom morphological data were available from serial CT scans were studied. Annualized growth rates based on diameter at presentation and time taken to reach a theoretical intervention threshold of 55 mm were calculated. The number of patients who would have achieved the threshold undetected was determined based on simulated imaging intervals of 6 months, 1, 2 and 3 years. RESULTS: A total of 2916 scans from 995 patients were analysed. The mean aortic expansion rate was 2·76 mm per year for all patients, with an exponential increase observed at sizes above 45 mm. Only 3·9 per cent of patients with a starting diameter of 30-39 mm and 5·3 per cent of those with a diameter of 40-44 mm achieved threshold size within 2 years. Conversely, the probability of expansion to more than 55 mm was 74·5 per cent in 2 years for patients with a starting diameter of 50-54 mm, rising to 85·7 per cent at 3 years. CONCLUSION: Based on a threshold of 55 mm for intervention, most patients with a maximum aortic diameter below 40 mm could safely undergo surveillance at 2-yearly intervals. Above 45 mm, annual surveillance is recommended. Patients with a diameter greater than 50 mm could be optimized for possible repair, if this is clinically appropriate.

Comparison of long-term mortality after ruptured abdominal aortic aneurysm in England and Sweden.

BACKGROUND: Concern has been raised regarding international discrepancies in perioperative mortality after repair of ruptured abdominal aortic aneurysm (rAAA). The variation in in-hospital mortality is difficult to interpret, owing to international differences in discharge strategies. This study compared 90-day and 5-year mortality in patients who had a rAAA in England and Sweden. METHODS: Patients undergoing rAAA repair were identified from English Hospital Episode Statistics and the Swedish Vascular Registry (Swedvasc) between 2003 and 2012. Ninety-day and 5-year mortality were compared after matching for age and sex. Within-country analyses examined the impact of co-morbidity, teaching hospital status or hospital annual caseload, adjusted with causal inference techniques. RESULTS: Some 12 467 patients underwent rAAA repair in England, of whom 83.2 per cent were men; the median (i.q.r.) age was 75 (70-80) years. A total of 2829 Swedish patients underwent rAAA repair, of whom 81.3 per cent were men; their median (i.q.r.) age was 75 (69-80) years. The 90-day mortality rate was worse in England (44.0 per cent versus 33.4 per cent in Sweden; P < 0.001), as was 5-year mortality (freedom from mortality 38.6 versus 46.3 per cent respectively; P < 0.001). In England, lower mortality was seen in teaching hospitals with larger bed capacity, higher annual caseloads and greater use of endovascular aneurysm repair (EVAR). In Sweden, lower mortality was associated with EVAR, high annual caseload, or surgery on weekdays compared with weekends. CONCLUSION: Short- and long-term mortality after rAAA repair was higher in England. In both countries, mortality was lowest in centres performing greater numbers of AAA repairs per annum, and more EVAR procedures.

Cardiovascular risk prevention and all-cause mortality in primary care patients with an abdominal aortic aneurysm.

BACKGROUND: Perioperative mortality is low for patients undergoing abdominal aortic aneurysm (AAA) repair, but long-term survival remains poor. Although patients diagnosed with AAA have a significant burden of cardiovascular disease and associated risk factors, there is limited understanding of the contribution of cardiovascular risk management to long-term survival. METHODS: General practice records within The Health Improvement Network (THIN) were examined. Patients with a diagnosis of AAA and at least 1 year of registered medical history were identified from 2000 to 2012. Medical therapies for cardiovascular risk were classified as antiplatelet, statin or antihypertensive agents. Progression to death was investigated using the G-computation formula with time-dependent co-variables to account for differences in exposure to cardiovascular risk-modifying treatments and the confounding between exposure, co-morbidities and death. RESULTS: Some 12 485 patients had a recorded diagnosis of AAA. From 2000 to 2012, prescription of medications that modify cardiovascular risk increased: from 26·6 to 76·7 per cent for statins, from 56·5 to 73·9 per cent for antiplatelet agents and from 75·3 to 84·0 per cent for antihypertensive drugs. Adjusted Kaplan-Meier curves demonstrated a better 5-year survival rate in patients receiving statins (68·4 versus 42·2 per cent), antiplatelet agents (63·6 versus 39·7 per cent) or antihypertensive agents (61·5 versus 39·1 per cent), compared with rates in patients not receiving each therapy. CONCLUSION: Appropriate risk factor modification could significantly reduce long-term mortality in patients with AAA. In the UK, up to 30 per cent of patients are not currently receiving these medications.

Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age.

BACKGROUND: Epidemiological evidence suggests that routine vaccinations can have nontargeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acellular pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases. METHODS: HealthNuts is a population-based cohort in Melbourne, Australia. Twelve-month-old infants were skin prick-tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease. RESULTS: Of 4433 children, 109 (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI: 0.36-1.62, P = 0.49) or atopic sensitization (aOR: 0.66; 95% CI: 0.35-1.24, P = 0.19). Amongst secondary outcomes, delayed DTaP was associated with reduced eczema (aOR: 0.57; 95% CI: 0.34-0.97, P = 0.04) and reduced use of eczema medication (aOR: 0.45; 95% CI: 0.24-0.83, P = 0.01). CONCLUSIONS: There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.

Systematic Review of the Growth Rates and Influencing Factors in Thoracic Aortic Aneurysms.

OBJECTIVE/BACKGROUND: The growth rates of thoracic aortic aneurysms (TAAs) and factors influencing their expansion are poorly understood. This study aimed to review systematically published literature describing TAA expansion and examine factors that may be associated with this. METHODS: A comprehensive search of MEDLINE and Embase databases was performed until 30 April 2015. Studies describing rates of TAA growth were identified and systematically reviewed. Outcomes of interest were TAA growth rates and associated factors. Study quality was assessed using Scottish Intercollegiate Guidelines Network quality checklists for cohort studies. RESULTS: Eleven publications, involving 1383 patients, met the eligibility criteria and were included in the review. Included studies were generally low in quality. Aneurysm measurement and growth-rate estimation techniques were inconsistently reported. Mean growth rates for all TAAs ranged from 0.2 to 4.2 mm/year. Mean growth rates for ascending and aortic arch aneurysms ranged from 0.2 to 2.8 mm/year, while those for descending and thoracoabdominal aneurysms ranged from 1.9 to 3.4 mm/year in studies reporting according to anatomical location. Large aneurysm size, distal aneurysm locations, presence of Marfan's syndrome, and bicuspid aortic valve were consistently associated with accelerated TAA growth. Presence of chronic dissection and chronic obstructive pulmonary disorder were also implicated as risk factors for faster TAA growth. Associations between medical comorbidity and aneurysm expansion were conflicting. Previous aortic surgery and anticoagulants were reported to have a protective effect on aneurysm growth in two studies. CONCLUSION: There is a shortfall in the understanding of TAA expansion rates. Existing studies are heterogeneous in methodology and reported outcomes. Identified unifying themes suggest that TAAs grow at a slow rate with large presenting diameter, distal aneurysm, and history of bicuspid aortic valve or Marfan's syndrome serving as main risk factors for accelerated aneurysm growth. High-quality studies with a standardised approach to TAA growth assessment are required.

The Endovascular Sealing Device in Combination with Parallel Grafts for Treatment of Juxta/Suprarenal Abdominal Aortic Aneurysms: Short-term Results of a Novel Alternative.

BACKGROUND: The chimney technique using parallel grafts offers an alternative to fenestrated or branched endovascular solutions for juxtarenal and suprarenal aneurysms. Endograft deployment proximal to the renal or visceral ostia is combined with parallel stents to the aortic side branches. Application of the chimney technique using the Nellix device (Ch-EVAS) may offer some potential advantages with respect to the seal between the endograft and the parallel grafts. This study aimed to investigate the feasibility and efficacy of the Nellix endovascular aneurysm sealing (EVAS) system in conjunction with parallel grafts for the treatment of juxtarenal and suprarenal aneurysms. METHODS: A prospective evaluation of patients treated for juxtarenal and suprarenal non-ruptured aortic aneurysms using Ch-EVAS was undertaken in a single vascular unit. Patients were treated with this technique if they were unsuitable for either open repair or a custom-made complex branched/fenestrated endograft. Procedural, postoperative morbidity, and mortality data were recorded. RESULTS: Between March 2013 and April 2015, 28 patients were treated with Ch-EVAS. The median age was 75 years (range 60-87 years) and the median aneurysm diameter 66 mm (IQR 60-73 mm). Eight patients underwent suprarenal aneurysm repair including parallel grafts in the superior mesenteric artery and renal arteries. Five patients had a double chimney configuration; all the other patients were treated with a single chimney configuration. There was one 30-day or in-hospital mortality in a patient with a symptomatic aneurysm (4%) and three further deaths within 1 year of follow-up. One proximal type I endoleak and one type II endoleak occurred. Four patients underwent a reintervention. One patient experienced a transient ischemic attack and two patients suffered from a minor stroke (7%), therefore the total number of cerebrovascular complications was 11%. No patient required postoperative renal replacement therapy. CONCLUSIONS: Ch-EVAS appears to offer a feasible solution for juxtarenal and suprarenal aneurysms with adverse morphology. In this short-term follow-up endoleak rates were low and re-intervention rates were acceptable. Outcomes over extended follow-up will determine the application of this novel technique and better define which patients and aneurysm morphology can be treated effectively.

Mortality of emergency general surgical patients and associations with hospital structures and processes.

BACKGROUND: Variations in patient outcomes between providers have been described for emergency admissions, including general surgery. The aim of this study was to investigate whether differences in modifiable hospital structures and processes were associated with variance in mortality, amongst patients admitted for emergency colorectal laparotomy, peptic ulcer surgery, appendicectomy, hernia repair and pancreatitis. METHODS: Adult emergency admissions in the English NHS were extracted from the Hospital Episode Statistics between April 2005 and March 2010. The association between mortality and structure and process measures including medical and nursing staffing levels, critical care and operating theatre availability, radiology utilization, teaching hospital status and weekend admissions were investigated. RESULTS: There were 294 602 emergency admissions to 156 NHS Trusts (hospital systems) with a 30-day mortality of 4.2%. Trust-level mortality rates for this cohort ranged from 1.6 to 8.0%. The lowest mortality rates were observed in Trusts with higher levels of medical and nursing staffing, and a greater number of operating theatres and critical care beds relative to provider size. Higher mortality rates were seen in patients admitted to hospital at weekends [OR 1.11 (95% CI 1.06-1.17) P<0.0001], in Trusts with fewer general surgical doctors [1.07 (1.01-1.13) P=0.019] and with lower nursing staff ratios [1.07 (1.01-1.13) P=0.024]. CONCLUSIONS: Significant differences between Trusts were identified in staffing and other infrastructure resources for patients admitted with an emergency general surgical diagnosis. Associations between these factors and mortality rates suggest that potentially modifiable factors exist that relate to patient outcomes, and warrant further investigation.

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts.

BACKGROUND: Models that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma. OBJECTIVE: To characterize the patterns of peripheral blood mononuclear cells' (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population-based birth cohorts using machine learning techniques. METHODS: PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 µg/ml). Cytokine expression (IL-13, IL-5, IFN-γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping. RESULTS: A six-class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: 'Nonresponders' (n = 905, 55%); 'IL-10 responders' (n = 49, 3%); 'IFN-γ and IL-13 medium responders' (n = 56, 3.4%); 'IL-13 medium responders' (n = 351, 21.4%); 'IL-5 and IL-13 medium responders' (n = 77, 4.7%); and 'IL-13 and IL-5 high responders' (n = 204, 12.4%). 'IL-13 and IL-5 high responders' were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma. CONCLUSION: Using model-based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL-13 and IL-5), and clinical outcomes. 'IL-13 and IL-5 high responders' class was strongly associated with HDM sensitization. However, among HDM-sensitized children, one-third showed no PBMC response to HDM, and the majority of HDM-sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM 'allergy tests' and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine-targeted treatment approaches.

Association of hospital structures with mortality from ruptured abdominal aortic aneurysm.

BACKGROUND: There is significant variation in the mortality rates of patients with a ruptured abdominal aortic aneurysm (rAAA) admitted to hospital in England. This study sought to investigate whether modifiable differences in hospital structures and processes were associated with differences in patient outcome. METHODS: Patients diagnosed with rAAA between 2005 and 2010 were extracted from the Hospital Episode Statistics database. After risk adjustment, hospitals were grouped into low-mortality outlier, expected mortality and high-mortality outlier categories. Hospital Trust-level structure and process variables were compared between categories, and tested for an association with risk-adjusted 90-day mortality and non-corrective treatment (palliation) rate using binary logistic regression models. RESULTS: There were 9877 patients admitted to 153 English NHS Trusts with an rAAA during the study. The overall combined (operative and non-operative) mortality rate was 67·5 per cent (palliation rate 41·6 per cent). Seven hospital Trusts (4·6 per cent) were high-mortality and 15 (9·8 per cent) were low-mortality outliers. Low-mortality outliers used significantly greater mean resources per bed (doctors: 0·922 versus 0·513, P < 0·001; consultant doctors: 0·316 versus 0·168, P < 0·001; nurses: 2·341 versus 1·770, P < 0·001; critical care beds: 0·045 versus 0·019, P < 0·001; operating theatres: 0·027 versus 0·019, P = 0·002) and performed more fluoroscopies (mean 12·6 versus 9·2 per bed; P = 0·046) than high-mortality outlier hospital Trusts. On multivariable analysis, greater numbers of consultants, nurses and fluoroscopies, teaching status, weekday admission and rAAA volume were independent predictors of lower mortality and, excluding rAAA volume, a lower rate of palliation. CONCLUSION: The variability in rAAA outcome in English National Health Service hospital Trusts is associated with modifiable hospital resources. Such information should be used to inform any proposed quality improvement programme surrounding rAAA.

International validation of a risk score for complications and reinterventions after endovascular aneurysm repair.

BACKGROUND: Lifelong surveillance is considered mandatory after endovascular repair (EVAR) of abdominal aortic aneurysms to detect endograft complications and prevent aneurysm rupture. Current protocols are not cost-effective or clinically effective. The international validity of the St George's Vascular Institute (SGVI) score for EVAR complications was examined. METHODS: The ENGAGE registry recruited patients undergoing EVAR at 79 centres in 30 countries. Reinterventions and endograft complications were recorded for up to 3 years after surgery. Preoperative aneurysm morphology was extracted from the registry database, and used to predict whether patients would be at low or high risk of complications after EVAR based on the SGVI score. Kaplan-Meier analysis was used to compare the incidence of endograft complications and reinterventions in patients predicted to be at low risk compared with those predicted to be at high risk. RESULTS: Some 1207 patients underwent EVAR, with follow-up of up to 3 years. The SGVI score accurately discriminated freedom from reinterventions (90·5 versus 79·3 per cent in low- versus high-risk patients; P < 0·001), freedom from endograft complications (77·9 versus 69·6 per cent in low- versus high-risk patients; P = 0·012), and freedom from a composite outcome measure of reinterventions or endograft complications (75·0 versus 66·1 per cent in low- versus high-risk patients; P = 0·006) during mid-term follow-up. CONCLUSION: This study has provided international validation of a morphological risk score that predicts mid-term reinterventions and endograft complications. The results may enable risk-stratified surveillance after EVAR.

Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969-2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies.

BACKGROUND: Improved critical care, pre-operative optimization, and the advent of endovascular surgery (EVAR) have improved 30 day mortality for elective abdominal aortic aneurysm (AAA) repair. It remains unknown whether this has translated into improvements in long-term survival, particularly because these factors have also encouraged the treatment of older patients with greater comorbidity. The aim of this study was to quantify how 5 year survival after elective AAA repair has changed over time. METHODS: A systematic review was performed identifying studies reporting 5 year survival after elective infrarenal AAA repair. An electronic search of the Embase and Medline databases was conducted to January 2014. Thirty-six studies, 60 study arms, and 107,814 patients were identified. Meta-analyses were conducted to determine 5 year survival and to report whether 5 year survival changed over time. RESULTS: Five-year survival was 69% (95% CI 67 to 71%, I(2) = 87%). Meta-regression on study midpoint showed no improvement in 5 year survival over the period 1969-2011 (log OR -0.001, 95% CI -0.014-0.012). Larger average aneurysm diameter was associated with poorer 5 year survival (adjusted log OR -0.058, 95% CI -0.095 to -0.021, I(2) = 85%). Older average patient age at surgery was associated with poorer 5 year survival (adjusted log OR -0.118, 95% CI -0.142 to -0.094, I(2) = 70%). After adjusting for average patient age, an improvement in 5 year survival over the period that these data spanned was obtained (adjusted log OR 0.027, 95% CI 0.012 to 0.042). CONCLUSION: Five-year survival remains poor after elective AAA repair despite advances in short-term outcomes and is associated with AAA diameter and patient age at the time of surgery. Age-adjusted survival appears to have improved; however, this cohort as a whole continues to have poor long-term survival. Research in this field should attempt to improve the life expectancy of patients with repaired AAA and to optimise patient selection.