Mapping national surveillance of surgical site infections in England: needs and priorities.

BACKGROUND: The rise in antimicrobial resistance has highlighted the importance of surgical site infection (SSI) prevention with effective surveillance strategies playing a key role in improving patient safety. AIM: To map national needs and priorities for SSI surveillance against current national surveillance activity. METHODS: This study analysed SSI surveillance in National Health Service (NHS) hospitals in England covering 23 surgical procedures. Data collected were: (i) annual number of procedures, (ii) SSI rates from national reports, (iii) national reporting requirement (mandatory, voluntary, not offered), (iv) priority ranking from a survey of 84 English NHS hospitals, (v) excess length of stay and costs from the literature. The relationships between estimated SSI burden, national surveillance activity, and hospital-reported priorities were explored with descriptive and univariate analyses. FINDINGS: Among the 23 surgical categories analysed, top priority ranking by hospitals was associated only with current surveillance (r = 0.76, P < 0.01) and mandatory reporting (33% vs 8 and 4%, P = 0.04). Percentage of hospitals undertaking surveillance, mandatory reporting, and the selection of priorities did not match SSI burden. Large bowel surgery (LBS, voluntary) and caesarean section (not offered) were the two highest contributors of total SSIs per annum, with 39,000 (38%) and 17,000 (16%) respectively, while the four orthopaedic categories (all mandatory) contributed 5000 (5%). LBS also had the highest associated costs (£119 million per annum). CONCLUSION: Current surveillance and future priorities were not associated with SSI rate, volume, or cost to hospitals. The two highest contributors of SSIs and related costs have no (caesarean section) or limited (LBS) coverage by national surveillance.

Regional variation in the management of metastatic gastric cancer in Ontario.

BACKGROUND: Geographic variation in cancer care is common when clear clinical management guidelines do not exist. In the present study, we sought to describe health care resource consumption by patients with metastatic gastric cancer (gc) and to investigate the possibility of regional variation. METHODS: In this population-based cohort study of patients with stage iv gastric adenocarcinoma diagnosed between 1 April 2005 and 31 March 2008, chart review and administrative health care data were linked to study resource utilization outcomes (for example, clinical investigations, treatments) in the province of Ontario. The study took a health care system perspective with a 2-year time frame. Chi-square tests were used to compare proportions of resource utilization, and analysis of variance compared mean per-patient resource consumption between geographic regions. RESULTS: A cohort of 1433 patients received 4690 endoscopic investigations, 12,033 computed tomography exams, 12,774 radiography exams, and 5059 ultrasonography exams. Nearly all patients were seen by a general practitioner (98%) and a specialist (99%), and were hospitalized (95%) or visited the emergency department (87%). Fewer than half received chemotherapy (43%), gastrectomy (37%), or radiotherapy (28%). The mean number of clinical investigations, physician visits, hospitalizations, and instances of patient accessing the emergency department or receiving radiotherapy or stent placement varied significantly by region. CONCLUSIONS: Variations in health care resource utilization for metastatic gc patients are observed across the regions of Ontario. Whether those differences reflect differential access to resources, patient preference, or physician preference is not known. The observed variation might reflect a lack of guidelines based on high-quality evidence and could partly be ameliorated with regionalization of gc care to high-volume centres.

Unabsorbed dura patch removed eight years after pituitary surgery.

The Codman ETHISORB Dura Patch is a synthetic, absorbable material whose absorption is complete within approximately 90 days. We report the first case of an unabsorbed Codman Dura patch, in which a patient was presented with nasal obstruction and epistaxis 8 years after pituitary surgery for Cushing's disease.

Clostridium difficile toxin testing by National Health Service (NHS) acute Trusts in England: 2008-2013.

In October 2007, a governmental 3-year target to reduce Clostridium difficile infection (CDI) by 30%, with financial penalties levied for failure, was introduced in England. This target was met within just 1 year, leading to speculation of 'gaming', with hospitals empirically treating possible CDI in the absence of a microbiological diagnosis, to avoid having to report confirmed cases. An analysis of aggregate mandatory data on levels of testing for C. difficile toxin showed little evidence of a fall in testing during the steepest infection rate reductions, suggesting that this was not a major factor in the decline in CDI.

Antibacterial usage in English NHS hospitals as part of a national Antimicrobial Stewardship Programme.

Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic organisms becoming resistant to commonly used antimicrobials. Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice, has become a key method of preventing the rise in the rise in AMR. Data on antibiotic consumption are often obtained through prospective and retrospective point prevalence audits of antibiotic usage, but such studies are very resource intensive and only provide a snapshot of consumption. The objective of the study reported here was to examine longitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital Trusts.

[An interesting experience on the use of information and population data bases]. / Una experiencia interesante en el uso de la información y de las bases de datos poblacionales.

INTRODUCTION: In order to support decisions and analyze outcomes, the Spanish Health System has shown a great interest in developing data bases and high quality information systems. Nevertheless the use of these data bases are limited, not very systematized and, some times, their accessibility may be difficult. MATERIAL AND METHODS: We describe in this review the experience in using the Institute for Clinical Evaluative Science (ICES, Ontario, Canada) as an efficient model to improve the usefulness of these data bases. RESULTS: Under restrictive conditions of confidentiality and privacy, the ICES has the legal capacity to use several population based data bases, for research projects and reports. ICES's functional structure (with an administrative and scientific level) is an interesting framework since it guarantees its independent and economic assessment. DISCUSSION: To date, its scientific production has been high in many areas of knowledge and open to those interested, with points of view of many health care professionals (including management), for whom the quality of research is of the ultimate importance, to be able to access these resources.

Indolinones and anilinophthalazines differentially target VEGF-A- and basic fibroblast growth factor-mediated responses in primary human endothelial cells.

BACKGROUND AND PURPOSE: The potent pro-angiogenic growth factors VEGF-A and basic fibroblast growth factor (bFGF) exert their effects by binding VEGF receptor 2 and FGF receptor tyrosine kinases, respectively. Indolinones (e.g. SU5416 and Sutent) and anilinophthalazines (e.g. PTK787) are potent small molecule inhibitors of VEGFR2 and other tyrosine kinases, but their effects on VEGF-A- and bFGF-stimulated endothelial responses are unclear. Here we assess the ability of these compounds to inhibit pro-angiogenic responses through perturbation of receptor activity and endothelial function(s). EXPERIMENTAL APPROACH: We used in silico modelling, in vitro tyrosine kinase assays, biochemistry and microscopy to evaluate the effects of small molecules on receptor tyrosine kinase activation and intracellular signalling. Primary human endothelial cells were used to assess intracellular signalling, cell migration, proliferation and tubulogenesis. KEY RESULTS: We predicted that the anilinophthalazine PTK787 binds the tyrosine kinase activation loop whereas indolinones are predicted to bind within the hinge region of the split kinase domain. Sutent is a potent inhibitor of both VEGFR2 and FGFR1 tyrosine kinase activity in vitro. The compounds inhibit both ligand-dependent and -independent VEGFR2 trafficking events, are not selective for endothelial cell responses and inhibit both VEGF-A- and bFGF-mediated migration, wound healing and tubulogenesis at low concentrations. CONCLUSIONS AND IMPLICATIONS; We propose that these compounds have novel properties including inhibition of bFGF-mediated endothelial responses and perturbation of VEGFR2 trafficking. Differential inhibitor binding to receptor tyrosine kinases translates into more potent inhibition of bFGF- and VEGF-A-mediated intracellular signalling, cell migration and tubulogenesis. Indolinones and anilinophthalazines thus belong to a class of multi-kinase inhibitors that show clinical efficacy in disease therapy.

A combinatorial in silico and cellular approach to identify a new class of compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis.

BACKGROUND AND PURPOSE: Vascular endothelial growth factor receptor 2 (VEGFR2) is an attractive therapeutic target for the treatment of diseases such as cancer. Small-molecule VEGFR2 inhibitors of a variety of chemical classes are currently under development or in clinical use. In this study, we describe the de novo design of a new generation pyrazole-based molecule (JK-P3) that targets VEGFR2 kinase activity and angiogenesis. EXPERIMENTAL APPROACH: JK-P compound series were designed using de novo structure-based identification methods. Compounds were tested in an in vitro VEGFR2 kinase assay. Using primary endothelial cells, JK-P compounds were assessed for their ability to inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling. We tested these compounds in cell migration, proliferation and angiogenesis assays. KEY RESULTS: JK-P3 and JK-P5 were predicted to bind the VEGFR2 kinase domain with high affinity, and both compounds showed pronounced inhibition of endogenous VEGFR2 kinase activity in primary human endothelial cells. Only JK-P3 inhibited VEGF-A-stimulated VEGFR2 activation and intracellular signalling. Interestingly, JK-P3 inhibited endothelial monolayer wound closure and angiogenesis but not endothelial cell proliferation. Both compounds inhibited fibroblast growth factor receptor kinase activity in vitro, but not basic fibroblast growth factor-mediated signalling in endothelial cells. CONCLUSIONS AND IMPLICATIONS: This is the first report that describes an anti-angiogenic inhibitor based on such a pyrazole core. Using a de novo structure-based identification approach is an attractive method to aid such drug discovery. These results thus provide an important basis for the development of multi-tyrosine kinase inhibitors for clinical use in the near future.

Enhanced surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland.

OBJECTIVE: To determine the incidence and demographic features of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland and to characterise MRSA isolated from cases. DESIGN: Prospective surveillance study. SETTING: Children aged <16 years hospitalised with bacteraemia due to MRSA. METHODS: Cases were ascertained by active surveillance involving paediatricians reporting to the British Paediatric Surveillance Unit and by routine laboratory surveillance. Patient characteristics were obtained using questionnaires sent to reporting paediatricians. MRSA isolates were characterised using molecular and phenotypic techniques including antimicrobial susceptibility testing. RESULTS: 265 episodes of MRSA bacteraemia were ascertained, involving 252 children. The overall incidence rate was 1.1 per 100 000 child population per year (95% CI 0.9 to 1.2): 61% of the children were aged <1 year (a rate of 9.7 cases per 100 000 population per year (95% CI 8.2 to 11.4)) and 35% were <1 month. Clinical data were obtained from 115 cases. The clinical presentation varied, with fever present in only 16% of neonates compared with 72% of older children. A history of invasive procedure was common, with 32% having had intravascular lines and 13% having undergone surgery. 62% of patients for whom data were available were receiving high-dependency care (46% in SCBU/NICU and 16% in PICU). Of 93 MRSA isolates studied, 73% belonged to epidemic strains widely associated with nosocomial infection in the UK and Ireland. CONCLUSIONS: MRSA bacteraemia in children was relatively uncommon and was predominantly seen in very young children, often those receiving neonatal or paediatric intensive care. Bacteraemia predominantly involved well-documented epidemic strains of MRSA associated with nosocomial infection.

Resource utilisation and costs of palliative cancer care in an interdisciplinary health care model.

This paper presents a detailed description of health care resource utilisation and costs of a pilot interdisciplinary health care model of palliative home care in Ontario, Canada. The descriptive evaluation entailed examining the use of services and costs of the pilot program: patient demographics, length of stay broken down by disposition (discharged, alive, death), access to services/resources, use of family physician and specialist services, and drug use. There were 434 patients included in the pilot program. Total costs were approximately CAN$2.4 million, and the cost per person amounted to approximately CAN$5586.33 with average length of stay equal to over 2 months (64.22 days). One may assume that length of stay would be influenced by the amount of service and support available. Future research might investigate whether in-home palliative home care is the most cost effective and suitable care setting for those patients requiring home care services for expected periods of time.

Derivatives of pyrimidine, phthalimide and anthranilic acid as inhibitors of human hydroxysteroid dehydrogenase AKR1C1.

Human hydroxysteroid dehydrogenase (HSD) AKR1C1 is a member of the aldo-keto reductase superfamily, and it functions mainly as a 20alpha-HSD. It catalyzes the reduction of the potent progesterone to the weak 20alpha-hydroxyprogesterone, and of 3alpha,5alpha-tetrahydroprogesterone (5alpha-THP; allopregnanolone) to 5alpha-pregnane-3alpha,20alpha-diol. AKR1C1 thus decreases the levels of progesterone and 5alpha-THP in peripheral tissue. Progesterone inhibits cell proliferation, stimulates differentiation of endometrial cells, and is also important for maintenance of pregnancy, while 5alpha-THP allosterically modulates the activity of the gamma-aminobutyric acid receptor. Inhibitors of AKR1C1 are thus potential agents for treatment of endometrial cancer and endometriosis, as well as other diseases like premenstrual syndrome, catamenial epilepsy and depressive disorders.We have synthesized a series of pyrimidine, phthalimido and athranilic acid derivatives, and have here examined their inhibitory properties towards AKR1C1. A common aldo-keto reductase substrate, 1-acenaphthenol, was used to monitor the NAD(+)-dependent oxidation catalyzed by AKR1C1. The most potent inhibitors of AKR1C1 were the pyrimidine derivative N-benzyl-2-(2-(4-methoxybenzyl)-6-oxo-1,6-dihydropyrimidin-4-yl)acetamide (K(i)=17 microM) and the anthranilic acid derivative 2-(((2',3-dichlorobiphenyl-4-yl)carbonyl)(methyl)amino)benzoic acid (K(i)=33 microM), both of which are non-competitive inhibitors.

Empty sella syndrome associated with a hyperfunctioning microadenoma invading the clivus.

The empty sella syndrome is usually associated with normal pituitary function. If dysfunction is present, this is commonly hypofunction. Hyperfunctioning microadenomas have been described in the presence of the empty sella syndrome. We present the first reported cases of a microadenoma invading the clivus associated with an empty sella.

A haemangiopericytoma of the ethmoid sinus causing oncogenic osteomalacia: a case report and review of the literature.

Oncogenic osteomalacia is a rare cause of osteomalacia. It is caused by a tumour which is generally benign. These tumours, when identified, are often found in the head and neck region. The case is reported here of a haemangiopericytoma isolated in the ethmoid sinus, and the literature regarding tumours at this site is reviewed. Including the present case there are five reported in the world literature of an ethmoid sinus tumour causing oncogenic osteomalacia. The treatment for this disease is excision of the mass, which is where the head and neck specialist's expertise is required.

Pseudoaneurysm after total pharyngolaryngectomy with jejunal graft insertion: two different presentations.

Pharyngeal reconstruction after total pharyngolaryngectomy using a jejunal graft is now a common procedure in head and neck oncological surgery. The vascular supply of this graft comes from the anastomosis between a branch of the mesentric artery and a branch of the external carotid artery. We report two cases of pseudoaneurysm, one at the site of ligation of the lingual artery and the other at the site of arterial anastomosis. One presented with dramatic hematemesis and was managed by the interventional radiologist, and the second presented with a pulsating neck mass and required a surgical revision. In both cases, the jejunal graft survived.

Haemangiopericytoma of the submental region.

Haemangiopericytoma refers to an uncommon vascular/perivascular neoplasm of which a minority of cases arise in the head and neck. It comprises a group of lesions with marked clinical and pathological heterogeneity and a lack of positive criteria by which to make a definitive diagnosis. We describe an unusual case of such a tumour in the submental region, review its pathological features and discuss issues in management and prognosis.

Who performs thyroid surgery: a review of current otolaryngological practice.

Thyroid surgery has been traditionally a general surgical practice, but recently more otolaryngologists have been offering a thyroid service. We have quantified thyroid surgery performed by the different specialties, and looked more closely at the practice of otolaryngologists. Data was obtained from the Department of Health for UK thyroid surgery in all specialties for the year 1998-99 and validated against a survey of members of the British Association of Otolaryngologists-Head & Neck Surgeons (BAO-HNS). The use of investigations of a simple clinical case (solitary thyroid nodule) was compared with best practice. General surgeons still perform the majority of thyroid surgery (83%) but ENT surgeons now perform significant numbers (15.4% of all cases), which translates to 1499 cases per annum. A total of 102 BAO-HNS members were performing thyroid surgery with an average case-load of 19.1 per year. In total, 35% of ENT surgeons see thyroid patients in multidisciplinary clinics. The choice of investigation is consistent with European guidelines. ENT surgeons are doing significant amounts of thyroid surgery and the numbers appear to be increasing. The formation of multidisciplinary teams including general surgeons and otolaryngologists who are committed to subspecialization can only improve both training and treatment outcomes.

NF kappa B and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells.

The ability to induce cellular defense mechanisms in response to environmental challenges is a fundamental property of eukaryotic and prokaryotic cells. We have previously shown that oxidative challenges lead to an increase in antioxidant enzymes, particularly glutathione peroxidase (GPx) and catalase (CAT), in mouse skeletal muscle. The focus of the current studies is the transcriptional regulatory mechanisms responsible for these increases. Sequence analysis of the mouse GPx and CAT genes revealed putative binding motifs for NF kappa B and AP-1, transcriptional regulators that are activated in response to oxidative stress in various tissues. To test whether NF kappa B or AP-1 might be mediating the induction of GPx and CAT in muscle cells subjected to oxidative stress, we first characterized their activation by pro-oxidants. Electrophoretic mobility shift assays showed that oxidative stress led to increases in the DNA binding of NF kappa B in differentiated muscle cells. The NF kappa B complexes included a p50/p65 heterodimer, a p50 homodimer, and a p50/RelB heterodimer. AP-1 was also activated, but with slower kinetics than that of NF kappa B. The major component of the AP-1 complexes was a heterodimer composed of c-jun/fos. To test for redox regulation of NF kappa B- or AP-1-dependent transcriptional activation, muscle cells expressing either kappa B/luciferase or TRE/luciferase reporter constructs were subjected to oxidative stress. Pro-oxidant treatment resulted in increased luciferase activity in cells expressing either construct. To test whether NF kappa B mediates oxidant-induced increases of GPx and CAT expression, we transfected cells with either a transdominant inhibitor (I kappa B alpha) or a dominant-negative inhibitor (Delta SP) of NF kappa B. Both inhibitors blocked the induction of antioxidant gene expression by more than 50%. In summary, our results suggest that NF kappa B and AP-1 are important mediators of redox-responsive gene expression in skeletal muscle, and that at least NF kappa B is actively involved in the upregulation of the GPx and CAT in response to oxidative stress.

Activity of the ketolide telithromycin (HMR-3647) against erythromycin-susceptible and -resistant pneumococci isolated in the UK.

The novel ketolide telithromycin (formerly HMR-3647) was tested against a collection of pneumococci of varying sensitivity to erythromycin and clindamycin, isolated in geographically diverse UK hospitals. Telithromycin was highly active against erythromycin-susceptible pneumococci, the MIC(90) being 0.015 mg/l. Erythromycin-resistant pneumococci that contained the ermB gene, either alone or together with the mefE gene, were cross-resistant to other macrolides and to clindamycin, while erythromycin-resistant pneumococci that contained only the mefE gene were cross-resistant to azithromycin, clarithromycin and roxithromycin but remained susceptible to josamycin and clindamycin. Telithromycin was active against erythromycin-resistant pneumococci irrespective of their mechanism of macrolide resistance, although the MIC(90) (0.25 mg/l) was higher than that seen with erythromycin-sensitive isolates. Telithromycin thus appears to be a potentially useful drug in settings where pneumococcal resistance to macrolides is prevalent.

What is the value of ENT specialist outreach clinics?

Ear, nose and throat (ENT) specialist outreach clinics, in which hospital-based consultants hold clinics in general practice surgeries, have been popular with general practitioners (GPs) and patients. This prospective study recorded data on 1155 consecutive patients seen by one ENT surgeon in two GP surgeries. At each consultation, a record was kept of the requirement for further investigations that would normally be done at the same time as the consultation in a hospital department. The results showed that 76 per cent of patients needed an investigation, which would be readily available in a hospital but not in a GP surgery (audiometry, endoscopy, microscopy of the ear, a minor procedure or X-ray). This study indicates that despite the apparent convenience of outreach ENT clinics to patients and GPs, patients may need to spend more time being assessed than they would if they were investigated in one visit to a hospital department. Unless an outreach clinic is used frequently, it is difficult to justify the cost of equipping it to the same level as a hospital department. Limited resources would be better spent providing good access to well-equipped regularly-used hospital ENT outpatient departments.