International Validation of a Methicillin-Resistant Staphylococcus aureus Risk Assessment Tool for Skin and Soft Tissue Infections.

INTRODUCTION: To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally. METHODS: A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined. RESULTS: Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P < 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678-0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569-0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716-0.845)] was significantly greater than surveillance percentage (P < 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less. CONCLUSION: The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation.

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

Long-COVID: An evolving problem with an extensive impact.

Persistence of symptoms or development of new symptoms relating to SARS-CoV-2 infection late in the course of COVID-19 is an increasingly recognised problem facing the globally infected population and its health systems. 'Long-COVID' or 'COVID long-haulers' generally describes those persons with COVID-19 who experience symptoms for >28 days after diagnosis, whether laboratory confirmed or clinical. Symptoms are as markedly heterogeneous as seen in acute COVID-19 and may be constant, fluctuate, or appear and be replaced by symptoms relating to other systems with varying frequency. Such multisystem involvement requires a holistic approach to management of long-COVID, and descriptions of cohorts from low- and middle-income countries are eagerly awaited. Although many persons with long-COVID will be managed in primary care, others will require greater input from rehabilitation medicine experts. For both eventualities, planning is urgently required to ensure that the South African public health service is ready and able to respond.

International Program to Monitor Cat Flea Populations for Susceptibility to Imidacloprid.

An international team of scientists and veterinarians was assembled in 1999 to develop a monitoring program to determine the susceptibility of cat fleas, Ctenocephalides felis felis (Bouché) (Siphonaptera: Pulicidae), to imidacloprid. Cat flea eggs were collected, shipped to laboratories, and tested for their susceptibility to imidacloprid. Over 3,000 C. felis populations were collected from 2002 to 2017 from 10 different countries. Of these, 66.3% were collected from cats and 33.7% from dogs. C. f. felis populations (n = 2,200) were bioassayed by exposing cat flea eggs and the emerging larvae to a Diagnostic Dose (DD) of 3 ppm imidacloprid in larval rearing medium. Flea eggs hatched and developed in the untreated controls in 1,837 of the isolates (83.5%) bioassayed. Flea isolates (n = 61) that had ≥5% survival at the DD of 3 ppm were retested with a second DD of 3 ppm. None of them had ≥5% survival to the second dose of 3 ppm. Of the 1,837 valid C. felis isolates tested, there has been no evidence of a decreased susceptibility to imidacloprid over the past 17 yr. The methods outlined in this article should provide an acceptable protocol for testing many of the new active ingredients that have been registered for cat flea control.

Surveillance of women with a personal history of breast cancer by tumour subtype.

AIM: To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. MATERIALS AND METHODS: A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. RESULTS: Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; p<0.002). Patients with triple-negative breast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. CONCLUSION: There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours.

BI-RADS® fifth edition: A summary of changes.

The Breast Imaging Reporting and Data System (BI-RADS®) is a standardized system of reporting breast pathology as seen on mammogram, ultrasound, and magnetic resonance imaging. It encourages consistency between reports and facilitates clear communication between the radiologist and other physicians by providing a lexicon of descriptors, a reporting structure that relates assessment categories to management recommendations, and a framework for data collection and auditing. This article highlights the changes made to the BI-RADS® atlas 5th edition by comparison with its predecessor, provide a useful resource for a radiologist attempting to review the recent changes to the new edition, and serve as a quick reference to those who have previously become familiar with the material.

A multi-centre clinical evaluation of reactive oxygen topical wound gel in 114 wounds.

OBJECTIVE: This article reports the outcomes of the use of Surgihoney RO (SHRO), topical wound dressing in a multi-centre, international setting. The aims were to explore the clinical effects of SHRO, including a reduction in bacterial load and biofilm and improvement in healing in a variety of challenging non-healing and clinically infected wounds. METHOD: This was a non-comparative evaluation, where both acute and chronic wounds with established delayed healing were treated with the dressing. Clinicians prospectively recorded wound improvement or deterioration, level of wound exudate, presence of pain, and presence of slough and necrosis. Analysis of this data provided information on clinical performance of the dressing. Semi-quantitative culture to assess bacterial bioburden was performed where possible. RESULTS: We recruited 104 patients, mean age 61 years old, with 114 wounds. The mean duration of wounds before treatment was 3.7 months and the mean duration of treatment was 25.7 days. During treatment 24 wounds (21%) healed and the remaining 90 (79%) wounds improved following application of the dressing. No deterioration in any wound was observed. A reduction in patient pain, level of wound exudate and in devitalised tissue were consistently reported. These positive improvements in wound progress were reflected in the wound cultures that showed a reduction in bacterial load in 39 out of the 40 swabs taken. There were two adverse events recorded: a stinging sensation following application of the dressing was experienced by 2 patients, and 2 elderly patients died of causes unrelated to the dressing or to the chronic wound. These patients' wounds and their response to SHRO have been included in the analysis. CONCLUSION: SHRO was well tolerated and shows great promise as an effective potent topical antimicrobial in the healing of challenging wounds. DECLARATION OF INTEREST: Matthew Dryden has become a shareholder in Matoke Holdings, the manufacturer of Surgihoney RO, since the completion of this study. Keith Cutting is a consultant to Matoke Holdings.

In vitro activity of an engineered honey, medical-grade honeys, and antimicrobial wound dressings against biofilm-producing clinical bacterial isolates.

OBJECTIVE: Honey is recognised to be a good topical wound care agent owing to a broad-spectrum of antimicrobial activity combined with healing properties. Surgihoney RO (SH1) is a product based on honey that is engineered to produce enhanced reactive oxygen species (ROS) and has been reported to be highly antimicrobial. The objective was to investigate the ability of the engineered honey and its comparators to prevent biofilm formation in vitro. METHOD: We tested the ability of three medical-grade honeys SH1, Activon manuka honey (MH) and Medihoney manuka honey (Med), alongside five antimicrobial dressings (AMDs) to prevent the formation of biofilms by 16 isolates. Honeys were serially double diluted from 1:3 down to 1:6144 and the lowest dilution achieving a statistically significant reduction in biomass of at least 50%, compared with untreated controls, was recorded. RESULTS: Although all the honeys were antibacterial and were able to prevent the formation of biofilms, SH1 was the most potent, with efficacy at lower dilutions than the medical honeys for five isolates, and equivalent dilutions for a further six. Additionally, SH1 was superior in antibacterial potency to three commercially available AMDs that contain honey. CONCLUSION: SH1 is effective at preventing bioflms from forming and is superior to medical honeys and AMDs in in vitro tests. DECLARATION OF INTEREST: Surgihoney RO was provided free of charge for testing by Matoke Holdings, UK and the hospital pharmacy provided the other honeys and dressings. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Procalcitonin levels predict infectious complications and response to treatment in patients undergoing cytoreductive surgery for peritoneal malignancy.

BACKGROUND: Cytoreductive-surgery for peritoneal-malignancy (PM) involves extensive intra-abdominal surgery and a massive post-operative systemic-inflammatory-response (SIRS). It is often challenging to differentiate SIRS that are solely surgery-associated from those of post-operative infections. White-Cell-Counts (WCC) and C-Reactive-Protein (CRP) are routinely used as markers for infection, but are non-specific and their elevation is often delayed in PM cases. Other markers need to be evaluated to assist early identification/prediction of post-operative infections. METHODOLOGY: Prospective evaluation of serum procalcitonin (PCT), CRP and WCC in 50 patients pre-operatively (Day0), and on post-operative days (POD) 1, 3 & 6, following cytoreductive-surgery with or without splenectomy. RESULTS: Day0 PCT, CRP and WCC values were within normal limits, but increasing physiologically in post-operative period without infection, with noticeable higher PCT in splenectomized patients. In our cohort post-operative infections were diagnosed in 14 patients, often within 48 h. There was a trend for faster rise in serum PCT on POD1 compared to CRP and WCC, and faster PCT decline following appropriate therapy on POD3 and POD6 when infected cases were clinically resolving while WCC and CRP continued to rise, particularly in non-spelenectomised patients. The AUC on POD1 was significantly higher for PCT (0.689) vs. WCC (0.476) and CRP (0.477) (p = 0.04). Sensitivity, specificity, positive-predictive-value and negative-predictive-values for PCT ranged between (57%-100%), (22%-74%), (33%-47%) & (81%-100%), for CRP (28%-78%), (5.5%-86%), (18%-44.4%) & (40%-75.5%) and for WCC (14%-26.5%), (65.5-80.5%), (22%-25%), (67%-70%) respectively. CONCLUSION: PCT, like WCC and CRP, needs to be interpreted with extreme cautions in the context of infections post-cytoreductive-surgery and should only be used in association with other clinical and investigational findings.

Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections.

Diabetes mellitus affects 284 million adults worldwide and is increasing in prevalence. Accelerated atherosclerosis in patients with diabetes mellitus contributes an increased risk of developing cardiovascular diseases including peripheral vascular disease (PVD). Immune dysfunction, diabetic neuropathy and poor circulation in patients with diabetes mellitus, especially those with PVD, place these patients at high risk for many types of typical and atypical infections. Complicated skin and soft-tissue infections (cSSTIs) are of particular concern because skin breakdown in patients with advanced diabetes mellitus and PVD provides a portal of entry for bacteria. Patients with diabetes mellitus are more likely to be hospitalized with cSSTIs and to experience related complications than patients without diabetes mellitus. Patients with PVD requiring lower extremity bypass are also at high risk of surgical site and graft infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent causative pathogen in cSSTIs, and may be a significant contributor to surgical site infections, especially in patients who are colonized with MRSA on hospital admission. Patients with cSSTIs and diabetes mellitus or PVD experience lower clinical success rates than patients without these comorbidities, and may also have a longer length of hospital stay and higher risk of adverse drug events. Clinicians should be vigilant in recognizing the potential for infection with multi-drug-resistant organisms, especially MRSA, in these populations and initiating therapy with appropriate antibiotics.

Implementing criteria-based early switch/early discharge programmes: a European perspective.

Early switch (ES) from intravenous (IV) to oral antibiotic therapy programmes is increasingly included as a component of hospital antimicrobial stewardship initiatives that aim to optimize antimicrobial therapy while limiting toxicity and resistance. In terms of prioritizing the most cost-effective stewardship interventions, ES has been seen as a 'low-hanging fruit', which refers to selecting the most obtainable targets rather than confronting more complicated issues. Administration of highly bioavailable oral antibiotics should be considered for nearly all non-critically ill patients and has been recommended as an effective and safe strategy for over two decades. However, to accrue the most benefit from ES, it should be combined with an early discharge (ED) plan, protocol, or care pathway. Benefits of this combined approach include improved patient comfort and mobility, reduced incidence of IV-line-related adverse effects, reduced IV antimicrobial preparation time, decreased hospital stays, reduced antimicrobial purchasing and administration costs, decreased patient deconditioning, and shortened recovery times. Results from published studies document decreases in healthcare resource use and costs following implementation of ES programmes, which in most studies facilitate the opportunity for ED and ED programmes. Barriers to the implementation of these programmes include clinician misconceptions, practical considerations, organizational factors, and a striking lack of awareness of IV to oral switch guidance. These and other barriers will need to be addressed to maximize the effectiveness of ES and ED programmes. As national antimicrobial stewardship programmes dictate the inclusion of ES and ED programmes within healthcare facilities, programmes must be developed and success must be documented.

Lyme borreliosis in southern United Kingdom and a case for a new syndrome, chronic arthropod-borne neuropathy.

This series of serologically confirmed Lyme disease is the largest reported in the UK and represents 508 patients who presented to one hospital in the South of England between 1992 and 2012. The mean rate of borreliosis throughout this period was 9·8/100,000 population, much higher than the reported national rate of 1·7/100,000. The actual rate increased each year until 2009 when it levelled off. Patients clinically presented with rash (71%), neurological symptoms (16%, of whom half had VII cranial nerve palsies), arthropathy (8%), pyrexia (5%), cardiac abnormalities (1%) or other manifestations (<1%). Twenty percent of patients had additional non-specific symptoms of fatigue, myalgia, and cognitive changes. Serological diagnosis was with a two-tiered system of ELISA and immunoblot. There was a marked seasonal presentation in the summer months and in the first and sixth decades of life. A third of patients gave a clear history of a tick bite. The median interval between tick bite and clinical symptoms was 15 days [interquartile range (IQR) 9-28 days], with a further interval of 14 days to clinical diagnosis/treatment (IQR 2-31 days). Most cases were acquired locally and only 5% abroad. Patients responded to standard antibiotic therapy and recurrence or persistence was extremely rare. A second group of patients, not included in the clinical case series, were those who believed they had Lyme disease based on a probable tick bite but were seronegative by currently available validated tests and presented with subjective symptoms. This condition is often labelled chronic Lyme disease. These patients have a different disease from Lyme disease and therefore an alternative name, chronic arthropod-borne neuropathy (CAN), and case definition for this condition is proposed. We suggest that this chronic condition needs to be distinguished from Lyme disease, as calling the chronic illness 'Lyme disease' causes confusion to patients and physicians. We recommend research initiatives to investigate the aetiology, diagnosis and therapy of CAN.

Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA), a hidden resistant mechanism among clinically significant isolates in the Wessex region/UK.

PURPOSE: Methicillin-resistant Staphylococcus aureus (MRSA) is defined as S. aureus genetically having the mecA or mecC genes or phenotypically showing minimum inhibitory concentration (MIC) of oxacillin higher than 2 mg/L. However, recently, cefoxitin/oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) has been reported worldwide. Little is known about the prevalence and virulence of these strains among clinically significant isolates in the UK. The aims were to (1) investigate the prevalence of OS-MRSA in seven major hospitals in the Wessex region/UK from a cohort of 500 clinically significant phenotypically identified MSSA isolates, (2) genetically characterise OS-MRSA strains by pulsed-field gel electrophoresis (PFGE) and compare these to common UK epidemic strains; and (3) to determine Panton-Valentine leukocidin (PVL; lukFS) gene carriage rates among these isolates. RESULTS: OS-MRSA was found in six isolates (1.2 %) of phenotypically identified and reported MSSA isolates by conventional methods. PFGE showed OS-MRSA strains to be genetically diverse and distinct from the common UK epidemic strains EMRSA-15 and EMRSA-16. None of these OS-MRSA stains carried the genes encoding PVL; however, overall positivity rate for PVL was 4.4 %, much higher than the nationally reported rates of 2 % in the UK. CONCLUSION: There are still many unknowns regarding phenotypic and/or genetic characterization of the emerging OS-MRSA isolates in the UK and worldwide. Data regarding their epidemiology and optimal therapy for infection are limited and need further investigation not only in the UK, but also worldwide, as it is likely to have an impact on the empirical treatment of S. aureus infections.

The use of Surgihoney to prevent or eradicate bacterial colonisation in dressing oncology long vascular lines.

OBJECTIVE: A pilot evaluation was performed to assess the effects of Surgihoney, an engineered honey with highly active antimicrobial activity, on bacterial colonisation in long lines in oncology patients. METHOD: This prospective service evaluation was conducted at Hampshire Hospitals NHS Foundation Trust (HHFT) in England, UK, between 2012 and 2013. The study population consisted of oncology patients with central intravenous lines who were receiving outpatient chemotherapy. All patients were offered line dressing with or without Surgihoney, applied to the line exit site. RESULTS: The primary outcome measure of the study was the presence or absence of bacterial colonisation of the line site. There were 30 patients in each arm - with or without Surgihoney. In the Surgihoney arm, 2 patients with existing line site colonisation were cleared of bacterial colonisation and none acquired colonisation during the study period. In the non-treatment arm, 6 patients were colonised at the line site prior to screening or during the evaluation. Bacterial colonisation was maintained throughout the period. CONCLUSION: Surgihoney is an effective antimicrobial line-site dressing, significantly reducing line site colonisation and eradicating existing colonisation. It was well tolerated by the patients. DECLARATION OF INTEREST: Surgihoney supplies were donated by Healing Honey International (HHI) who also provided some funding to Hampshire Hospitals Foundation Trust for microbiological investigation. MD and JC have provided clinical advice in an advisory capacity to HHI.

European perspective and update on the management of complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid.

Complicated skin and soft tissue infections (cSSTIs) are a diverse group of infections, with a range of presentations and microbiological causes. Hospitalization is common for patients with a cSSTI, which is treated by drainage of the affected area and with antibiotics. Host factors such as co-morbidities, and microbial factors, in particular drug resistance, complicate the management of these infections. Methicillin-resistant Staphylococcus aureus (MRSA) is an important cSSTI pathogen in Europe, and its involvement can be associated with poor patient outcomes. European guidelines recommend vancomycin, teicoplanin, linezolid, daptomycin, tigecycline or ceftaroline for treatment of MRSA cSSTIs. Of primary importance when treating cSSTIs is the agent's clinical efficacy against the causative pathogens, as well as its bioavailability in the skin and associated structures. Linezolid is well-suited for the treatment of MRSA cSSTIs; it achieves high penetration into skin and soft tissues with 100% oral bioavailability, and therefore enables an intravenous to oral switch and outpatient treatment. When eligible patients are offered oral therapy the associated length of hospital stay and overall costs can be reduced. Linezolid has demonstrated clinical efficacy and favourable outcomes in patients for the treatment of MRSA cSSTIs including the treatment of lower extremity infections. Furthermore, efficacy has been documented in key defined populations, such as individuals with renal impairment and the obese. The safety profile of linezolid is well-documented, making this antibacterial a viable choice for the treatment of MRSA cSSTIs.

Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer†.

BACKGROUND: Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Phase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m(2) i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2) every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m(2) i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity. RESULTS: Sixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31-75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred. CONCLUSION: The addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. CLINICAL TRIAL NUMBER: NCT00499603.

Fusobacterium species infections: clinical spectrum and outcomes at a district general hospital.

PURPOSE: Fusobacterium species infections are rare. Recently, however, this potentially deadly pathogen has been attracting interest, and efforts are being made to characterise its epidemiology and clinical spectrum of disease. The aim of our study is to provide further evidence towards this cause, in what is, to date, the largest study of its kind from the UK. METHOD: A 22-year, retrospective, descriptive study was performed at Royal Hampshire County Hospital. An electronic database was used to identify patients with microbiologically confirmed infection with Fusobacterium, and clinical records were examined to provide further information on the presentation, source, treatment and outcome. RESULTS: Fusobacterium species infections were identified in 18 patients during the study period, which is an incidence of 0.76 cases/100,000/year. The overall death rate was 29 %. Half of these patients had Fusobacterium necrophorum infections and were a predominantly young, fit and uniquely male population who had excellent outcomes. Among the remaining patients with Fusobacterium species infections, 22 % had infection with F. varium and 11 % with F. nucleatum. These patients were an older cohort who tended to have co-morbidities and unsurprisingly worse outcomes. We identified a number of Fusobacterium bacteraemias likely to have resulted from pressure ulcers, a presentation that has been rarely reported. Interestingly, we also identified a case of neonatal F. nucleatum bacteraemia that was not associated with premature nor stillborn birth. CONCLUSION: As work continues to depict the spectrum of disease caused by this enigmatic bacterium, it is hoped that improved clinical suspicion will result in better outcomes and management.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition: guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestations on dogs and cats.

These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures.

Measuring synovial fluid procalcitonin levels in distinguishing cases of septic arthritis, including prosthetic joints, from other causes of arthritis and aseptic loosening.

OBJECTIVES: Differentiating septic arthritis from non-septic arthritis can be challenging as the clinical pictures are similar and an efficacious diagnostic test is not yet available. Our objectives in this study were to establish if procalcitonin (PCT) could be reproducibly measured from synovial fluid, if there is a difference in synovial procalcitonin values between patients with septic and non-septic arthritis, respectively, including those with implants and to determine cut-off levels that could be used as a practical tool in the management of these conditions. METHODS: Using a standard serum assay, synovial fluid PCT levels were measured retrospectively in 26 septic and 50 non-septic predefined arthritis cases. The reproducibility of synovial PCT was also assessed at various concentrations. RESULTS: Synovial PCT can be measured and is reproducible. In this cohort, statistically significant higher synovial PCT levels were found in cases of septic arthritis than in non-septic arthritis. Sensitivities, specificities and positive and negative predictive values varied at different cut-off levels. CONCLUSION: The test could be added to other microbiological and biochemical tests and may be used to supplement other clinical, radiological and laboratory findings in the assessment of patients with acute painful joints. In our cohort, findings of very high synovial PCT levels supported an infection process, including in prosthesis-related infections. The high negative predictive value of low synovial PCT levels could exclude infection in both native and prosthetic joints. Larger prospective studies are needed to further validate these results and to examine the cost effectiveness of synovial PCT.