Efficacy and cost effectiveness of bronchial arterial embolisation in the treatment of major haemoptysis

Objective. To determine the efficacy and cost-effectiveness of bronchial artery embolisation (BAE) in the treatment of major and massive haemop tysis in HIV-positive and negative patients with pulmonary inflammatory disease.Methods. A retrospective review of patients admitted over a period of 24 months to Wentworth Hospital with major haemoptysis treated using BAE.Results. Eighty-seven patients were treated (77 males, 10 females). Bilateral disease was present in 50 patients (57%). Thirty-two patients were lllV-positive (37%). Embolisation was successfully performed in 77 patients (88.5%), and failed for technical reasons in 10 patients (11 .5%). There was only one procedural complication. Fifty-seven patients had a successful outcome, with cessation of haemoptysis within 24 hours (66.5%). Haemoptysis continued in 30 patients (34%) (20 patients embolised and the 10 patients who had failed procedures). Fourteen of these patients (16%) required lobectomy or pneumonectomy as an emergency procedure. Five patients (5.7%) died from respiratory failure or pulmonary haemorrhage. Twenty-four HIV-positive patients were successfully embolised. Costing of BAE, including a 2-day ICU and 3-day ward stay, was R6 720; together with surgical resection the cost was R14 170.Conclusions. BAE is an effective treatment for major and/or massive haemoptysis in patients with pulmonary inflammatory disease who are not surgical candidates. Patients who are HIV-positive are able to tolerate the procedure well

Comparing computed tomography (CT) angiography versus digital subtraction angiography for the screening of traumatic pseudoaneurysms in transcranial stab injuries

Introduction: Transcranial stab injuries among the civilian population in South Africa are more common than in the West. In a study conducted in Durban, South Africa, in 1992, transcranial stab injuries accounted for 6% of all head injuries admitted to the neurosurgical unit. Digital subtraction angiography (DSA) has been the gold standard for diagnosing traumatic pseudoaneurysms. Its use as a screening tool is, however, limited and carries risks of neurological deficits. We postulate that the newer generation computed tomography (CT) scanner would serve as a better screening tool for traumatic pseudoaneurysms following transcranial stab injuries with the blade removed, provided the image quality is good. Methods: All patients admitted with a stab to the head with total calvarial penetration from September 2014 to January 2016 were included in the study. Those with a retained metallic fragment, incomplete imaging protocols, no penetration of the blade into the brain parenchyma or other causes of penetrating head injury were not included in the study. A retrospective chart review was then done on a prospectively recruited patient cohort. All CT angiograms were performed using a dual source CT scanner. Results: A total of 26 patients met the inclusion criteria. There were seven vascular injuries identified on DSA: three traumatic pseudoaneurysms and four vessel cut-offs. One traumatic pseudoaneurysm was missed on computed tomography angiography (CTA) because of a poor quality scan. The average sensitivity and specificity of CTA compared with DSA was 67% and 95.5%, respectively. Negative predictive value for CTA was 99.5%. Conclusion: A good quality CTA carried out on the newer generation CT scanners allows for use of CTA as a screening tool for patients with a transcranial stab injury and no retained blade or metallic foreign bodies

Childhood behavior problems and academic outcomes in adolescence: longitudinal population-based study

Abstract OBJECTIVE: To investigate the impact of increasing levels of inattention, hyperactivity/impulsivity, and oppositional/defiant behaviors at age 7 years on academic achievement at age 16 years. METHOD: In a population-based sample of 7-year-old children in England, information was obtained about inattention, hyperactivity/impulsivity, and oppositional/defiant behaviors (using parent and teacher ratings) and the presence of attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBDs). After adjusting for confounder variables, their associations with academic achievement in national General Certificate of Secondary Education (GCSE) examinations (using scores and minimum expected school-leaving qualification level [5 "good" GCSEs]) at age 16 years were investigated (N = 11,640). RESULTS: In adjusted analyses, there was a linear association between each 1-point increase in inattention symptoms and worse outcomes (2- to 3-point reduction in GCSE scores and 6% to 7% (10%-12% with teacher ratings) increased likelihood of not achieving 5 good GCSEs). ADHD was associated with a 27- to 32-point reduction in GCSE scores and, in boys, a more than 2-fold increased likelihood of not achieving 5 good GCSEs. In boys, oppositional/defiant behaviors were also independently associated with worse outcomes, and DBDs were associated with a 19-point reduction in GCSE scores and a 1.83-increased likelihood of not achieving 5 good GCSEs. CONCLUSION: Across the full range of scores at a population level, each 1-point increase in inattention at age 7 years is associated with worse academic outcomes at age 16. The findings highlight long-term academic risk associated with ADHD, particularly inattentive symptoms. After adjusting for inattention and ADHD respectively, oppositional/defiant behaviors and DBDs are also independently associated with worse academic outcomes

Predicting infectious complications in neutropenic children and young people with cancer (IPD protocol)

<p>Abstract</p> <p>Background</p> <p>A common and potentially life-threatening complication of the treatment of childhood cancer is infection, which frequently presents as fever with neutropenia. The standard management of such episodes is the extensive use of intravenous antibiotics, and though it produces excellent survival rates of over 95%, it greatly inconveniences the three-fourths of patients who do not require such aggressive treatment. There have been a number of studies which have aimed to develop risk prediction models to stratify treatment. Individual participant data (IPD) meta-analysis in therapeutic studies has been developed to improve the precision and reliability of answers to questions of treatment effect and recently have been suggested to be used to answer questions regarding prognosis and diagnosis to gain greater power from the frequently small individual studies.</p> <p>Design</p> <p>In the IPD protocol, we will collect and synthesise IPD from multiple studies and examine the outcomes of episodes of febrile neutropenia as a consequence of their treatment for malignant disease. We will develop and evaluate a risk stratification model using hierarchical regression models to stratify patients by their risk of experiencing adverse outcomes during an episode. We will also explore specific practical and methodological issues regarding adaptation of established techniques of IPD meta-analysis of interventions for use in synthesising evidence derived from IPD from multiple studies for use in predictive modelling contexts.</p> <p>Discussion</p> <p>Our aim in using this model is to define a group of individuals at low risk for febrile neutropenia who might be treated with reduced intensity or duration of antibiotic therapy and so reduce the inconvenience and cost of these episodes, as well as to define a group of patients at very high risk of complications who could be subject to more intensive therapies. The project will also help develop methods of IPD predictive modelling for use in future studies of risk prediction.</p

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research

Risk Factors for Revision of Polished Taper-Slip Cemented Stems for Periprosthetic Femoral Fracture After Primary Total Hip Replacement: A Registry-Based Cohort Study from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man

Background: Total hip replacement (THR) with a cemented polished taper-slip (PTS) femoral stem has excellent long-term results but is associated with a higher postoperative periprosthetic femoral fracture (PFF) risk compared with composite beam stems. This study aimed to identify risk factors associated with PFF revision following THR with PTS stems. Methods: In a retrospective cohort study, 299,019 primary THRs using PTS stems from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) were included, with a median follow-up of 5.2 years (interquartile range [IQR], 3.1 to 8.2 years). The adjusted hazard ratio (HR) of PFF revision was estimated for each variable using multivariable Cox survival regression analysis. Results: Of 299,019 THR cases, 1,055 underwent revision for PFF at a median time of 3.1 years (IQR, 1.0 to 6.1 years). The mean age (and standard deviation) was 72 ± 9.7 years, 64.3% (192,365 patients) were female, and 82.6% (247,126 patients) had an American Society of Anesthesiologists (ASA) class of 1 or 2. Variables associated with increased PFF were increasing age (HR, 1.02 per year), intraoperative fracture (HR, 2.57 [95% confidence interval (CI), 1.42 to 4.66]), ovaloid (HR, 1.96 [95% CI, 1.22 to 3.16]) and round cross-sectional shapes (HR, 9.58 [95% CI, 2.29 to 40.12]), increasing stem offset (HR, 1.07 per millimeter), increasing head size (HR, 1.04 per millimeter), THR performed from 2012 to 2016 (HR, 1.45 [95% CI, 1.18 to 1.78]), cobalt-chromium stem material (HR, 6.7 [95% CI, 3.0 to 15.4]), and cobalt-chromium stems with low-viscosity cement (HR, 22.88 [95% CI, 9.90 to 52.85]). Variables associated with a decreased risk of PFF revision were female sex (HR, 0.52 [95% CI, 0.45 to 0.59]), increasing stem length (HR, 0.97 per millimeter), and a ceramic-on-polyethylene bearing (HR, 0.55 [95% CI, 0.36 to 0.85]). Conclusions: Increased risk of PFF revision was associated with PTS stems that are short, have high offset, are used with large femoral heads, are made of cobalt-chromium, or have ovaloid or round cross-sectional shapes. Large increases in PFF risk were associated with cobalt-chromium stems used with low-viscosity cement. Further study is required to confirm causation. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

Present and Future of Surface-Enhanced Raman Scattering.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article

Effects of ecosystem protection on scallop populations within a community-led temperate marine reserve

This study investigated the effects of a newly established, fully protected marine reserve on benthic habitats and two commercially valuable species of scallop in Lamlash Bay, Isle of Arran, United Kingdom. Annual dive surveys from 2010 to 2013 showed the abundance of juvenile scallops to be significantly greater within the marine reserve than outside. Generalised linear models revealed this trend to be significantly related to the greater presence of macroalgae and hydroids growing within the boundaries of the reserve. These results suggest that structurally complex habitats growing within the reserve have substantially increased spat settlement and/or survival. The density of adult king scallops declined threefold with increasing distance from the boundaries of the reserve, indicating possible evidence of spillover or reduced fishing effort directly outside and around the marine reserve. However, there was no difference in the mean density of adult scallops between the reserve and outside. Finally, the mean age, size, and reproductive and exploitable biomass of king scallops were all significantly greater within the reserve. In contrast to king scallops, the population dynamics of queen scallops (Aequipecten opercularis) fluctuated randomly over the survey period and showed little difference between the reserve and outside. Overall, this study is consistent with the hypothesis that marine reserves can encourage the recovery of seafloor habitats, which, in turn, can benefit populations of commercially exploited species, emphasising the importance of marine reserves in the ecosystem-based management of fisheries

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes