Vocal palsy increases the risk of lower respiratory tract infection in low-risk, low-morbidity patients undergoing thyroidectomy for benign disease: A big data analysis.

OBJECTIVES: Thyroidectomy is the commonest operation that places normally functioning laryngeal nerves at risk of injury. Vocal palsy is a major risk factor for dysphonia, dysphagia, and less commonly, airway obstruction. We investigated the association between post-thyroidectomy vocal palsy and long-term risks of pneumonia and laryngeal failure. DESIGN: An N=near-all analysis of the English administrative dataset using a previously validated informatics algorithm to identify young and otherwise low-risk patients undergoing first-time elective thyroidectomy for benign disease. Information about age, sex, morbidities, social deprivation and post-operative and late complications were derived. MAIN OUTCOME MEASURES: Between 2004 and 2012, 43 515 patients between the ages of 20 and 69 who had no history of cancer, neurological, or respiratory disease underwent elective total or hemithyroidectomy without concomitant or late neck dissection, parathyroidectomy or laryngotracheal surgery for benign thyroid disease for the first and only time. Information about age, sex, morbidities and in-hospital and late complications was recorded. RESULTS: Mean age at surgery was 46±12. There was a strong female preponderance (85%), and most patients (89%) had no recorded Charlson comorbidities Most patients (65%) underwent hemithyroidectomy. Late vocal palsy was recorded in 449 (1.03%) patients, and its occurrence was an independent risk factor for emergency hospital readmission (n=7113; Hazard Ratio 1.52; 95% confidence interval 1.21-1.91), hospitalisation for lower respiratory tract infection (n=944; HR 2.04; 95% CI 1.07-3.75), dysphagia (n=564; HR 3.47; 95% CI 1.57-7.65) and gastrostomy/tracheostomy placement (n=80; HR 20.8; 95% CI 2.5-171.2). Independent risk factors for late vocal palsy were age, burden of morbidities, total thyroidectomy, post operative bleeding, male sex, and annual surgeon volume <30. CONCLUSIONS: There is a significant association between post-thyroidectomy vocal palsy and long-term risks of hospital readmission, dysphagia, hospitalisation for lower respiratory tract infection, and gastrostomy/tracheostomy tube placement. This adds weight to the need, from a thyroid surgical perspective, to undertake universal post-thyroidectomy laryngeal surveillance as a minimum standard of care, with a focus on post-operative dysphagia and aspiration, and from a medical/respiratory perspective, to initiate investigations to identify occult vocal palsy in patients who present with pneumonia, who have a history of thyroid surgery.

Impact of the method and success of pharyngeal reconstruction on the outcome of treating laryngeal and hypopharyngeal cancers with pharyngolaryngectomy: A national analysis.

BACKGROUND: Surgical treatment of cancers that arise from or invade the hypopharynx presents major reconstructive challenges. Reconstructive failure exposes the airway and neck vessels to digestive contents. METHODS: We performed a national N = near-all analysis of the administrative dataset to identify pharyngolaryngectomies in England between 2002 and 2012. Information about morbidity, pharyngeal closure method and post-operative complications was derived. RESULTS: There were 1589 predominantly male (78%) patients whose mean age at surgery was 62 years. The commonest morbidities were hypertension (24%) and ischemic heart disease (11%). For 232 (15%) patients, pharyngolaryngectomy was performed during an emergency admission. The pharynx was closed primarily in 551 patients, with skin or muscle free or pedicled flaps in 755 patients and with jejunum and gastric pull-up in 123 and 160 patients, respectively. In-hospital mortality rate was 6% and was significantly higher in the gastric pull-up group (11%). Reconstructive failure had an odds ratio of 6.2 [95% confidence interval (CI) 2.4-16.1] for in-hospital death. The five-year survival was 57% and age, morbidities, emergency surgery, gastric pull-up, major acute cardiovascular events, renal failure and reconstructive failure independently worsened prognosis. Patients who underwent pharyngeal reconstruction with radial forearm or anterolateral thigh flaps had lower mortality rates than patients who had jejunum flap reconstruction (hazard ratio = 1.50 [95% CI 1.03-2.19]) or gastric pull-up (hazard ratio = 1.92 [95% CI 1.32-2.80]). CONCLUSIONS: Pharyngolaryngectomy carries a high degree of risk of morbidity and mortality. Reconstructive failure worsens short- and long-term prognosis, and the use of cutaneous free flaps appears to improve survival.

A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics-based Outcomes Surveillance Framework.

OBJECTIVES: To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data. DESIGN: A Hospital Episode Statistics N = near-all analysis. SETTINGS: The English National Health Service. MAIN OUTCOME MEASURES: Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in-hospital mortality were recorded. RESULTS: Within local audit datasets, the accuracy of assigning newly-derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 ± 12 years. The commonest cancer site strata were oral cavity (42%) and larynx-hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap-based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio-economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in-hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in-hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in-hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral-pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics-based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset.

A national analysis of trends, outcomes and volume-outcome relationships in thyroid surgery.

OBJECTIVES: Thyroid conditions are common, and their incidence is increasing. Surgery is the mainstay treatment for many thyroid conditions, and understanding its utilisation trends and morbidity is central to improving patient care. DESIGN: An N = near-all analysis of the English administrative dataset to identify trends in thyroid surgery specialisation, volume-outcome relationships, and the incidence and risk factors for short- and long-term morbidity. MAIN OUTCOME MEASURES: Between 2004 and 2012, 72 594 patients underwent elective thyroidectomy in England. Information about age, sex, morbidities, nature of thyroid disease and surgery, adjuvant treatments and complications including hypocalcaemia and vocal palsy was recorded. RESULTS: Mean age at surgery was 49 ± 30, and a female predominance (82%) was observed. Most patients underwent hemithyroidectomy (51%) or total thyroidectomy (32%). Patients underwent surgery for benign (52.5%), benign inflammatory (21%) and malignant (17%) thyroid diseases. Thyroid surgery grew by 2.9% a year and increased in specialisation. Increased surgeon volume significantly reduced lengths of stay: the proportion of length of stay outliers fell from 11.8% for patients of occasional thyroidectomists (<5 per year) to 2.8% for patients of high-volume surgeons (>50 thyroidectomies a year). Post-discharge vocal palsy and hypocalcaemia occurred in 1.87% and 1.58% of cases, respectively. High-volume surgeons had a reduced incidence of vocal palsy, and volumes >30 were consistently protective. CONCLUSIONS: Thyroid surgery is increasingly specialised. High-volume surgeons, that is patients who perform 50 or more thyroidectomies per year, achieve lower complications and shorter lengths of stay.

Role of reconstructive surgery in the management of head and neck cancer: a national outcomes analysis of 11,841 reconstructions.

BACKGROUND: The quality of head and neck cancer reconstruction in England is not known. Hospital administrative data provides details of treatment within the English National Health Service and may be used for national outcomes analysis. METHODS: An algorithm for identifying head and neck surgery with flap-based reconstruction from administrative data was constructed and validated against information from three cancer units. The validated algorithm was applied to 2003-2013 national activity. RESULTS: The algorithm was 91% sensitive and over 99% specific. Its application to administrative data identified 11,841 patients and demonstrated an increase of 52% in reconstruction-containing head and neck cancer surgery in the past decade. There were 7776 males and mean treatment age was 62 years. Oral cavity was the commonest primary site (n = 7567; 64%) and 7575 patients (64%) underwent primary surgery. The commonest procedure was floor-of-mouth excision (n = 3614) and 9749 patients had a neck dissection. The most commonly used flap was the radial forearm (n = 4429). Flap failure occurred in 496 (4.2%) patients. It increased the mean length of stay from 22 to 41 days (P < 0.00001), and the odds ratio of in-hospital death to 2.37 [95% confidence interval 1.66-3.38; P < 0.0001]. Lethality of reconstructive failure was not uniform and was highest when a pharyngolaryngeal flap failed. CONCLUSIONS: Reconstructive surgery is central to the multidisciplinary management of head and neck cancer. Its quality directly influences patient morbidity and survival. We recommend that analysis of hospital administrative data should be periodically carried out as part of an over-arching quality assurance programme and, particularly for pharyngolaryngeal reconstructions, surgery should be undertaken in units with the best reconstructive outcomes.

A national analysis of the outcome of major head and neck cancer surgery: implications for surgeon-level data publication.

OBJECTIVES: To undertake a national outcomes analysis following major head and neck cancer surgery in order to identify risk factors for complications and in-hospital mortality, as well as areas whose closer examination and formal benchmarking in the context of local and national quality assurance audits may lead to improved results for this condition. DESIGN: An analysis using Hospital Episode Statistics data. SETTINGS: All units undertaking major head and neck cancer surgery in England. MAIN OUTCOME MEASURES: Cancer sites, co-morbidities, social deprivation, surgical and non-surgical treatments, complications, and in-hospital mortality were recorded. Regression analysis was used for casemix adjustment and for identifying independent predictors of complications and mortality. Funnel plots were used for data visualisation. RESULTS: We identified 10,589 major head and neck cancer operations performed in England between 2006 and 2011. There were 7312 males, and mean age at surgery was 63 ± 13 years. Oral cavity (42%) and the larynx (28%) were the commonest cancer sites. At least one complication occurred in 33.1% of patients, and there were 322 (3.05%) in-hospital deaths. Variables associated with in-hospital mortality were trust volume, age, co-morbidities, performing emergency major surgery and performing a tracheostomy or reconstructive surgery. Occurrence of major medical complications including pulmonary infections (7%), major acute cardiovascular events (4.7%) and acute renal failure (0.6%) also increased mortality risk. The analysis identified units that were outside of crude and risk-adjusted 99.8% limits of confidence for complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows significant national variation and is associated with fixed risk factors like age and co-morbidities, but also with modifiable risk factors like performing major surgery during an emergency admission, tracheostomy, reconstructive surgery and medical complications. We propose that the quality of tracheostomy care, reconstructive surgery, emergency major surgery rate, and occurrence and treatment of major medical complications should be closely examined and formally benchmarked as part of loco-regional and national quality improvement audits.

Radiosurgery planning supported by the GEMSS grid.

GEMSS (Grid Enabled Medical Simulation Services IST-2001-37153) is an EU project funded to provide a test bed for Grid-enabled health applications. Its purpose is evaluation of Grid computing in the health sector. The health context imposes particular constraints on Grid infrastructure design, and it is this that has driven the feature set of the middleware. In addition to security, the time critical nature of health applications is accommodated by a Quality of Service component, and support for a well defined business model is also included. This paper documents experience of a GEMSS compliant radiosurgery application running within the Medical Physics department at the Royal Hallamshire Hospital in the UK. An outline of the Grid-enabled RAPT radiosurgery application is presented and preliminary experience of its use in the hospital environment is reported. The performance of the software is compared against GammaPlan (an industry standard) and advantages/disadvantages are highlighted. The RAPT software relies on features of the GEMSS middleware that are integral to the success of this application, and together they provide a glimpse of an enabling technology that can impact upon patient management in the 21st century.

GEMSS: grid-infrastructure for medical service provision.

OBJECTIVES: The European GEMSS Project is concerned with the creation of medical Grid service prototypes and their evaluation in a secure service-oriented infrastructure for distributed on demand/supercomputing. Key aspects of the GEMSS Grid middleware include negotiable QoS support for time-critical service provision, flexible support for business models, and security at all levels in order to ensure privacy of patient data as well as compliance to EU law. METHODS: The GEMSS Grid infrastructure is based on a service-oriented architecture and is being built on top of existing standard Grid and Web technologies. The GEMSS infrastructure offers a generic Grid service provision framework that hides the complexity of transforming existing applications into Grid services. For the development of client-side applications or portals, a pluggable component framework has been developed, providing developers with full control over business processes, service discovery, QoS negotiation, and workflow, while keeping their underlying implementation hidden from view. RESULTS: A first version of the GEMSS Grid infrastructure is operational and has been used for the set-up of a Grid test-bed deploying six medical Grid service prototypes including maxillo-facial surgery simulation, neuro-surgery support, radio-surgery planning, inhaled drug-delivery simulation, cardiovascular simulation and advanced image reconstruction. CONCLUSIONS: The GEMSS Grid infrastructure is based on standard Web Services technology with an anticipated future transition path towards the OGSA standard proposed by the Global Grid Forum. GEMSS demonstrates that the Grid can be used to provide medical practitioners and researchers with access to advanced simulation and image processing services for improved preoperative planning and near real-time surgical support.

GEMSS: privacy and security for a medical Grid.

OBJECTIVES: The GEMSS project is developing a secure Grid infrastructure through which six medical simulations services can be invoked. We examine the legal and security framework within which GEMSS operates. METHODS: We provide a legal qualification to the operations performed upon patient data, in view of EU directive 95/46, when using medical applications on the GEMSS Grid. We identify appropriate measures to ensure security and describe the legal rationale behind our choice of security technology. RESULTS: Our legal analysis demonstrates there must be an identified controller (typically a hospital) of patient data. The controller must then choose a processor (in this context a Grid service provider) that provides sufficient guarantees with respect to the security of their technical and organizational data processing procedures. These guarantees must ensure a level of security appropriate to the risks, with due regard to the state of the art and the cost of their implementation. Our security solutions are based on a public key infrastructure (PKI), transport level security and end-to-end security mechanisms in line with the web service (WS Security, WS Trust and SecureConversation) security specifications. CONCLUSION: The GEMSS infrastructure ensures a degree of protection of patient data that is appropriate for the health care sector, and is in line with the European directives. We hope that GEMSS will become synonymous with high security data processing, providing a framework by which GEMSS service providers can provide the security guarantees required by hospitals with regard to the processing of patient data.

AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.

A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.

Thymus-dependent, anti-CD4-induced tolerance to rat cardiac allografts.

BACKGROUND: Treatment with anti-CD4 monoclonal antibodies (mAbs) leads to induction of transplant tolerance in rodent models, but the cellular mechanisms responsible are poorly defined. In this study, we used a rat model of cardiac transplantation to examine the contribution of the thymus gland to anti-CD4 mAb-induced tolerance. METHODS: Pretransplant administration of OX38 mAb partially depletes peripheral CD4 T cells and induces tolerance to fully allogeneic Lewis (RT1l) heterotopic cardiac allografts in DA (RT1a) recipients. Using this experimental model, the contribution of the adult thymus gland and of recent thymic emigrants to tolerance induction was assessed, and the cellular and humoral alloimmune responses accompanying tolerance defined. RESULTS: OX38 mAb selectively depleted mature CD4 T cells but spared CD4 T cells that had recently emerged from the thymus. Pretransplant thymectomy abrogated tolerance induction, but the data suggested a role for recent thymic emigrants rather than for the thymus gland per se. Both nonrejecting cardiac allografts in OX38-treated recipients and rejecting grafts in control animals were infiltrated to a similar extent by mononuclear cells, including activated T cells. Intragraft mRNA transcripts for interleukin (IL)-2, interferon-gamma, IL-4, IL-10, and IL-13 were similar in non-rejecting and rejecting allografts although, with the exception of IL-2, there was a trend towards reduced cytokine transcripts in tolerant grafts. CD4 T cells from long-term tolerant recipients proliferated normally to donor alloantigen in vitro, and produced IL-2, interferon-gamma, and IL-4 in amounts comparable to normal CD4 T cells. Tolerant recipients also developed a strong alloantibody response comprising both IgG1 (Th2-dependent) and IgG2b (Th1-dependent) subclasses. CONCLUSIONS: The results of this study suggest that the thymus, through the production of recent thymic emigrants, plays an important role in facilitating the induction of transplant tolerance after anti-CD4 mAb. Tolerant animals displayed strong cell-mediated and humoral alloimmune responses with no evidence of selective deviation from a Th1 to a Th2-like cytokine pattern.

Alloantibody and intragraft cellular response to MHC class I-disparate kidney allografts in recipients tolerized by donor-specific transfusion and cyclosporine.

Congenic PVG.RT1u rats rapidly reject Aa class I-disparate kidney allografts from recombinant PVG R8 donors and we recently demonstrated that anti-class I MHC alloantibody plays a critical role in effecting acute rejection in this experimental model. In this article, we show that PVG.RT1u recipients can be rendered permanently and specifically tolerant to R8 kidney allografts by administration of four weekly donor-specific transfusions (DST) combined with a 7-day course of cyclosporine given with the first DST. Tolerance induction correlated with abrogation of a cytotoxic alloantibody response by thymus-independent, i.e., peripheral mechanisms; IgM and all IgG subclasses of anti-class I alloantibody were abolished. In contrast, nonrejecting kidney allografts in tolerant rats and rejecting grafts from unmodified recipients were similarly infiltrated by mononuclear cells, and intragraft transcripts for interleukin (IL)-2, interferon-gamma, and IL-13 were readily detected by reverse transcriptase polymerase chain reaction with no apparent quantitative difference between the two groups. Messenger RNA for IL-4 and IL-10 was present in rejecting grafts but barely detectable in grafts from tolerant animals. These results suggest that tolerance induction by DST and cyclosporine is, in this experimental model, associated with a selective impairment in humoral alloimmunity.

Semantic and visual factors affecting the representation of map information.

In past research evidence has been found for both mental imagery and propositional hierarchies in subjects' map representations. How the visual and semantic factors associated with maps influence the use of one form of representation or another was the subject of the study reported here. Subjects were required to make relational judgments about city pairs. The results of experiment 1 indicated that superordinate relationships (the relationship of the counties of which the cities were members) affected only the most difficult perceptual judgments, but affected all judgments made from memory. Experiment 2 was done to determine the extent to which these findings were attributable to perceptual distortions rather than propositionally stored rules. Results of experiment 3 showed the degree of perceptual distinction necessary for propositional rules to have no significant influence on relational judgments.