Value of risk scores in the decision to palliate patients withruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48‐h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C‐statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48‐h mortality in the IMPROVE data was reasonable (C‐statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C‐statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life‐saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non‐intervention rates, while respecting the wishes of the patient and family

Freezing and chemical preservatives alter the stable isotope values of carbon and nitrogen of the Asiatic clam (Corbicula fluminea)

We tested the impacts of most common sample preservation methods used for aquatic sample materials on the stable isotope ratios of carbon and nitrogen in clams, a typical baseline indicator organism for many aquatic food web studies utilising stable isotope analysis (SIA). In addition to common chemical preservatives ethanol and formalin, we also assessed the potential impacts of freezing on δ¹³C and δ¹⁵N values and compared the preserved samples against freshly dried and analysed samples. All preservation methods, including freezing, had significant impacts on δ¹³C and δ¹⁵N values and the effects in general were greater on the carbon isotope values (1.3-2.2% difference) than on the nitrogen isotope values (0.9-1.0% difference). However, the impacts produced by the preservation were rather consistent within each method during the whole 1 year experiment allowing these to be accounted for, if clams are intended for use in retrospective stable isotope studies

Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial

Objective To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. Design Randomised controlled trial. Setting 30 vascular centres (29 UK, 1 Canadian), 2009-13. Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. Interventions 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). Main outcome measures 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. Results 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval −£625 to £2997). Conclusions A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women

Genetic Predictions of Prion Disease Susceptibility in Carnivore Species Based on Variability of the Prion Gene Coding Region

Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrP(C)) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C) protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter

Comparative clinical effectiveness and cost effectiveness of endovascular strategy vs open repair for ruptured abdominal aortic aneurysm: three year results of the IMPROVE randomised trial

Objective To assess the three year clinical outcomes and cost effectiveness of a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair for patients with suspected ruptured abdominal aortic aneurysm. Design Randomised controlled trial. Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm, of whom 502 underwent emergency repair for rupture. Interventions 316 patients were randomised to an endovascular strategy (275 with confirmed rupture) and 297 to open repair (261 with confirmed rupture). Main outcome measures Mortality, with reinterventions after aneurysm repair, quality of life, and hospital costs to three years as secondary measures. Results The maximum follow-up for mortality was 7.1 years, with two patients in each group lost to follow-up by three years. After similar mortality by 90 days, in the mid-term (three months to three years) there were fewer deaths in the endovascular than the open repair group (hazard ratio 0.57, 95% confidence interval 0.36 to 0.90), but by seven years mortality was about 60% in each group (hazard ratio 0.92, 0.75 to 1.13). Results for the 502 patients with repaired ruptures were more pronounced: three year mortality was lower in the endovascular strategy group (42% v 54%; odds ratio 0.62, 0.43 to 0.88), but after seven years there was no clear difference between the groups (hazard ratio 0.86, 0.68 to 1.08). Reintervention rates up to three years were not significantly different between the randomised groups (hazard ratio 1.02, 0.79 to 1.32); the initial rapid rate of reinterventions was followed by a much slower mid-term reintervention rate in both groups. The early higher average quality of life in the endovascular strategy versus open repair group, coupled with the lower mortality at three years, led to a gain in average quality adjusted life years (QALYs) at three years of 0.17 (95% confidence interval 0.00 to 0.33). The endovascular strategy group spent fewer days in hospital and had lower average costs of −£2605 (€2813; $3439) (95% confidence interval −£5966 to £702). The probability that the endovascular strategy is cost effective was >90% at all levels of willingness to pay for a QALY gain. Conclusions At three years, compared with open repair, an endovascular strategy for suspected ruptured abdominal aortic aneurysm was associated with a survival advantage, a gain in QALYs, similar levels of reintervention, and reduced costs, and this strategy was cost effective. These findings support the increasing use of an endovascular strategy, with wider availability of emergency endovascular repair. Trial registration Current Controlled Trials ISRCTN48334791; ClinicalTrials NCT00746122This project was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project No 07/37/64). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, National Health Service, or the Department of Health. Neither the funder nor the sponsor had any role in study design, data collection, analysis and interpretation of the findings

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm

Background: Single-centre series of the management of patients with ruptured abdominal aortic aneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes. Methods: IMPROVE is a pragmatic, multicentre randomized clinical trial in which eligible patients with a clinical diagnosis of ruptured aneurysm were allocated to a strategy of endovascular aneurysm repair (EVAR) or to open repair. The influences of time and manner of hospital presentation, fluid volume status, type of anaesthesia, type of endovascular repair and time to aneurysm repair on 30-day mortality were investigated according to a prespecified plan, for the subgroup of patients with a proven diagnosis of ruptured or symptomatic AAA. Adjustment was made for potential confounding factors. Results: Some 558 of 613 randomized patients had a symptomatic or ruptured aneurysm: diagnostic accuracy was 91·0 per cent. Patients randomized outside routine working hours had higher operative mortality (adjusted odds ratio (OR) 1·47, 95 per cent confidence interval 1·00 to 2·17). Mortality rates after primary and secondary presentation were similar. Lowest systolic blood pressure was strongly and independently associated with 30-day mortality (51 per cent among those with pressure below 70 mmHg). Patients who received EVAR under local anaesthesia alone had greatly reduced 30-day mortality compared with those who had general anaesthesia (adjusted OR 0·27, 0·10 to 0·70). Conclusion: These findings suggest that the outcome of ruptured AAA might be improved by wider use of local anaesthesia for EVAR and that a minimum blood pressure of 70 mmHg is too low a threshold for permissive hypotension

GHQ increases among Scottish 15 year olds 1987–2006

BACKGROUND: Increases in a number of psychosocial disorders have been identified among Western youth in the second half of the Twentieth century. However findings are not consistent, trends are complex, and comparisons over time are hampered by methodological problems. METHODS: Data were drawn from three samples identical in respect of age (15 years), school year (final year of statutory schooling) and geographical location (the West of Scotland). Each sample was administered the 12-item General Health Questionnaire, a measure of self-report psychological distress, in 1987 (N = 505), 1999 (N = 2,196) and 2006 (N = 3,194). Analyses were conducted to examine changes in: GHQ 'caseness'; individual items; and factors, derived via confirmatory factor analysis representing (a) 'negative' and 'positive' items, and (b) 'anxiety and depression', 'loss of confidence or self-esteem' and 'anhedonia and social dysfunction'. RESULTS: Based on the standard (2/3) cut-off, 'caseness' rates in 1987, 1999 and 2006 were 12.7, 15.1 and 21.5% (males) and 18.8, 32.5 and 44.1% (females). Similar increases were observed with more stringent 'caseness' cut-offs. Examination of individual items showed some to have increased much more markedly over time than others. There were larger increases among females for all except two items and some evidence, among both genders, of steeper increases among 'negative' items compared with 'positive' ones. However, the differences in slope were very small compared with the overall increases in both types. CONCLUSIONS: Data from three samples identical in respect of age, school year and geographical location, show marked increases in GHQ-12 'caseness' among females between 1987 and 1999 and among both males and females between 1999 and 2006. Although slightly steeper increases in 'negative' items raise the possibility that endorsing such symptoms may have become more acceptable, these were small in comparison with increases in all dimensions of psychological distress. The next step is to identify causal explanations for the increases reported here

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

08.05.15 KB. OK to add published oa paper to spira