IMRiS phase II study of IMRT in limb sarcomas: Results of the pre-trial QA facility questionnaire and workshop.

INTRODUCTION: Soft tissue sarcomas of the extremities (STSE) are rare malignancies. We report current UK practice for immobilisation of soft tissue sarcoma of STSE, as part of the initial study set-up within the IMRiS trial, a phase II study of intensity modulated radiotherapy (IMRT) in primary bone and soft tissue sarcoma. METHODS: A facility questionnaire (FQ) was circulated to 29 IMRiS centres investigating the variation in immobilisation devices, planning techniques, and imaging protocols. A workshop was held to address concerns raised by centres. It focused on STSE immobilisation and patient set-up. Robustness of patient set-up at each centre was evaluated based on the following criteria: evidence of local set-up audit, calculation of margins based on set-up audit results, imaging frequency, and number of patients treated per centre per annum. RESULTS: Twenty-seven (93%) questionnaires were returned. 30% (8/27) of responders routinely treated STSE with IMRT. The remaining 70% (19/27) had little or no experience with IMRT for STSE. Vacuum bags were the most frequent immobilisation device (9/27), followed by thermoplastic shells (7/27). Nine centres had audited their local set-up; however, only 4 had calculated margins in response to the results. Ten centres were classified as having high level of robustness. CONCLUSIONS: Immobilisation devices and planning techniques for STSE are inconsistent across centres. Robustness of set-up is an important tool to ensure quality of results in a multicentre trial setting with such different levels of experience. The IMRiS trial Quality Assurance programme encourages centres to assess robustness of set-up through local audit and subsequent calculation of treatment margins. IMPLICATIONS FOR PRACTICE: This is the first study that used robustness criteria to tailor QA support to individual centres.

Is urethral microscopy useful in symptomatic male patients without urethral discharge?

National guidelines recommend that male patients presenting with symptoms of urethritis or epididymo-orchitis undergo a urethral swab for microscopy. However, this is resource intensive. The aim of this audit was to determine the proportion of symptomatic patients without urethral discharge who have positive findings on urethral swab microscopy and explore associations between presenting symptoms and microscopy findings. We conducted a retrospective audit of symptomatic male patients who underwent microscopy. There was a significant difference between the percentage of symptomatic patients with positive findings on microscopy in those with and without urethral discharge (67% vs 33%, p < 0.001). In a patient presenting with symptoms other than urethral discharge, the likelihood that positive findings on microscopy would occur in a patient with dysuria was 4.73 times more likely than if they did not have dysuria, when controlling for age, testicular pain or discomfort, and urethral discomfort or penile irritation (p < 0.01). In situations where there are limited resources, patients without urethral discharge presenting with dysuria could be prioritised. However, further research is required to identify and stratify which patients require microscopy.

Modifiable risk factors for external cause mortality after release from prison: a nested case-control study.

AIM: People released from prison are at higher risk of mortality from potentially preventable causes than their peers in the general population. Because most studies of this phenomenon are reliant on registry data, there is little health and behavioural information available on those at risk, hampering the development of targeted, evidence-based preventive responses. Our aim was to identify modifiable risk and protective factors for external cause and cause-specific mortality after release from prison. METHODS: We undertook a nested case-control study using data from a larger retrospective cohort study of mortality after release from prison in Queensland, Australia between 1994 and 2007. Cases were 286 individuals who had died from external causes (drug overdose, suicide, transport accidents, or violence) matched with 286 controls on sex, Indigenous status, and release date. We extracted data from detention, case-management, and prison medical records. RESULTS: Factors associated with increased risk of external cause mortality included use of heroin and other opioids in the community [odds ratio (OR) = 2.20, 95% CI 1.41-3.43, p < 0.001], a prescription for antidepressants during the current prison sentence (OR = 1.94, 95% CI 1.02-3.67, p = 0.042), a history of problematic alcohol use in the community (OR = 1.54, 95% CI 1.05-2.26, p = 0.028), and having ever served two or more custodial sentences (OR = 1.51, 95% CI 1.01-2.25, p = 0.045). Being married (OR = 0.45, 95% CI 0.29-0.70, p < 0.001) was protective. Fewer predictors were associated with cause-specific mortality. CONCLUSIONS: We identified several behavioural, psychosocial, and clinical markers associated with mortality from preventable causes in people released from prison. Emerging evidence points to interventions that could be targeted at those at increased risk of external cause mortality. These include treatment and harm reduction programmes (for substance use), improving transitional support programmes and continuity of care (for mental health), diversion and drug reform (for repeat incarceration) and nurturing stable relationships during incarceration. The period of imprisonment and shortly after release provides a unique opportunity to improve the long-term health of ex-prisoners and overcome the disadvantage associated with imprisonment.

Clinical haematology and biochemistry profiles of cattle naturally infected with Theileria orientalis Ikeda type in New Zealand.

AIMS: To present the haematology and biochemistry profiles for cattle in New Zealand naturally infected with Theileria orientalis Ikeda type and investigate if the results differed between adult dairy cattle and calves aged <6 months. METHODS: Haematology and biochemistry results were obtained from blood samples from cattle which tested positive for T. orientalis Ikeda type by PCR, that were submitted to veterinary laboratories in New Zealand between October 2012 and November 2014. Data sets for haematology and biochemistry results were prepared for adult dairy cattle (n=62 and 28, respectively) and calves aged <6 months (n=62 and 28, respectively), which were matched on the basis of individual haematocrit (HCT). Results were compared between age groups when categorised by HCT. Selected variables were plotted against individual HCT, and locally weighted scatterplot smoothing (Loess) curves were fitted to the data for adult dairy cattle and calves <6 months old. RESULTS: When categorised by HCT, the proportion of samples with HCT <0.15 L/L (severe anaemia) was greater for adult dairy cattle than for beef or dairy calves, for both haematology (p<0.002) and biochemistry (p<0.001) submissions. There were differences (p<0.05) between adult dairy cattle and calves aged <6 months in the relationships between HCT and red blood cell counts, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentrations, lymphocyte and eosinophil counts, and activities of glutamate dehydrogenase and aspartate aminotransferase. In both age groups anisocytosis was frequently recorded. The proportion of blood smears showing mild and moderate macrocytosis was greater in adults than calves (p=0.01), and mild and moderate poikilocytosis was greater in calves than adults (p=0.005). CONCLUSIONS AND CLINICAL RELEVANCE: The haematology and biochemistry changes observed in cattle infected with T. orientalis Ikeda type were consistent with extravascular haemolytic anaemia. Adult dairy cattle were more likely to be severely anaemic than calves. There were differences in haematology and biochemistry profiles between adult dairy cattle and calves, but most of these differences likely had a physiological rather than pathological basis. Overall, the haematological changes in calves aged <6 months appeared less severe than in adult dairy cattle.

Cluster analysis of the clinical histories of cattle affected with bovine anaemia associated with Theileria orientalis Ikeda type infection.

AIM To determine the most commonly used words in the clinical histories of animals naturally infected with Theileria orientalis Ikeda type; whether these words differed between cases categorised by age, farm type or haematocrit (HCT), and if there was any clustering of the common words in relation to these categories. METHODS Clinical histories were transcribed for 605 cases of bovine anaemia associated with T. orientalis (TABA), that were submitted to laboratories with blood samples which tested positive for T. orientalis Ikeda type infection by PCR analysis, between October 2012 and November 2014. χ2 tests were used to determine whether the proportion of submissions for each word was similar across the categories of HCT (normal, moderate anaemia or severe anaemia), farm type (dairy or beef) and age (young or old). Correspondence analysis (CA) was carried out on a contingency table of the frequency of the 28 most commonly used history words, cross-tabulated by age categories (young, old or unknown). Agglomerative hierarchical clustering, using Ward's method, was then performed on the coordinates from the correspondence analysis. RESULTS The six most commonly used history words were jaundice (204/605), lethargic (162/605), pale mucous membranes (161/605), cow (151/605), anaemia (147/605), and off milk (115/605). The proportion of cases with some history words differed between categories of age, farm type and HCT. The cluster analysis indicated that the recorded history words were grouped in two main clusters. The first included the words weight loss, tachycardia, pale mucous membranes, anaemia, lethargic and thin, and was associated with adult (p<0.001), severe anaemia (p<0.001) and dairy (p<0.001). The second cluster included the words deaths, ill-thrift, calves, calf and diarrhoea, and was associated with young (p<0.001), normal HCT (p<0.001), beef (p<0.001) and moderate anaemia (p<0.001). CONCLUSIONS AND CLINICAL RELEVANCE Cluster analysis of words recorded in clinical histories submitted with blood samples from cases of TABA indicates that two potentially different disease syndromes were associated with T. orientalis Ikeda type infection. One was consistent with the affected cattle suffering from a severe regenerative extravascular haemolytic anaemia, the second displaying as ill thrift and diarrhoea, particularly in young beef cattle.

A phase II study to determine the efficacy and safety of oral treosulfan in patients with advanced pre-treated Ewing sarcoma ISRCTN11631773.

We report a prospective Phase II study of efficacy and toxicity for oral treosulfan in advanced Ewing sarcoma. Twenty patients, median age 19 years (range 7-39) from five UK sites, were treated with oral treosulfan 1 g/m(2) daily for 7 days in 28. Primary endpoint was objective response rate. Best response was stable disease in one patient. All patients died of progressive disease, after median 6.41 months. Median progression free survival was 1.8 months. Toxicity was minimal. No activity was demonstrated for treosulfan at this dose. Progression free survival data should be able to be used for comparison when planning future clinical trials.

Paediatric head injury admissions over a 10-year period in a regional neurosurgical unit.

Traumatic brain injury is a leading cause of death and disability in childhood. A retrospective study of all paediatric head injuries admitted to the neurosurgical unit for the West of Scotland over a 10-year period was performed to assess the impact of the National Institute for Health and Clinical Excellence head injury guidelines on the admission rate and to determine the associated risk factors, causes, severity and outcomes of these injuries. There were 564 admissions between 1998 and 2007. The median age at presentation was nine years and two months. There was no change in the admission rate, injury mechanism or severity of head injury admitted over the period studied. A relationship was observed between the Scottish Index of Multiple Deprivation Score and the incidence of head injury (P = 0.05). Alcohol was reported as a causative factor in only a small number of cases, and moderate to severe head injuries were more commonly identified as a result of road traffic accidents.

Multi-drug-resistant Enterococcus spp. as a cause of non-responsive septic synovitis in three horses.

CASE HISTORY: Three Thoroughbred horses, a 6-week-old filly (Case 1), a 15-year-old broodmare (Case 2) and a yearling filly (Case 3), sustained synovial sepsis secondary to trauma. CLINICAL FINDINGS: Case 1 presented with a heel bulb laceration communicating with the distal interphalangeal joint. Arthroscopic lavage was performed and treatment commenced using systemic and local broad spectrum antimicrobial drugs. A pure growth of multi-drug-resistant (MDR) Enterococcus gallinarum was cultured from samples of synovium and joint fluid. Antimicrobial treatment was changed according to the susceptibility results. Response to treatment was poor and despite repeat arthroscopic lavage and intra-osseous regional perfusion of antimicrobials the filly was subject to euthanasia 24 days after the initial injury. Post-mortem examination confirmed septic synovitis, cartilage degeneration and osteomyelitis. Case 2 sustained a full thickness wound to the carpus which was sharply debrided and closed. The wound dehisced with effusion within the tendon sheath. Drainage was established and treatment included systemic broad spectrum antimicrobials, topical lavage with povodine-iodine and manuka honey infusion. A mixed infection including MDR Enterococcus faecalis was cultured from the synovial fluid. Antebrachiocarpal joint effusion developed 21 days after initial injury and joint sepsis was confirmed. Arthroscopic lavage and tendon sheath debridement were performed, followed by treatment with systemic and local antimicrobials. The mare improved and was discharged. Three months later lameness recurred and corticosteroids were administered intra-articularly. The mare became non-weight bearing lame and was subject to euthanasia. Post-mortem examination confirmed joint sepsis of the antebrachiocarpal and intercarpal joint. Case 3 presented with a complete articular open fracture of the tibial crest. Under general anaesthesia the fracture was stabilised and the wounds debrided and closed. Systemic broad-spectrum antimicrobials were administered. Six days later the wound dehisced and a bone fragment was removed. Three weeks post-surgery the wound deteriorated with a purulent discharge. Culture of the discharge revealed a mixed bacterial infection, including a MDR Enterococcus faecalis. Femoropatellar joint involvement was confirmed, and treatment included joint lavage, local and systemic antibiosis, and manuka honey instilled into the wound. The filly initially improved, and then deteriorated such that euthanasia was performed. DIAGNOSIS: All three cases had synovial sepsis with MDR Enterococcus spp. CLINICAL RELEVANCE: Increased awareness of MDR pathogens in equine wound infections is essential. Prompt diagnostic testing, appropriate therapy, infection control strategies and on-going monitoring and management are vital to limit the clinical impact of these organisms.

Cefixime-resistant Neisseria gonorrhoeae in the UK: a time to reflect on practice and recommendations.

A 40-year-old man who has sex with men (MSM) with urethral gonorrhoea failed to respond to treatment with 400 mg cefixime orally. Laboratory isolation of the post-treatment strain showed a minimum inhibitory concentration of ≥0.25 mg/L, which is a level of tolerance to cefixime that has not been previously documented in the UK. This case illustrates the importance of assessing all patients after treatment for gonorrhoea so that treatment failure and antibiotic resistance can be identified. It is vital that gonorrhoea culture continues to be attempted from all infected individuals to enable accurate diagnosis and antibiotic sensitivities. We also recommend that laboratories test for cefixime sensitivity routinely, given that it is one of the most commonly prescribed treatments for gonorrhoea.

Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study.

OBJECTIVES: Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. METHODS: Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL). RESULTS: Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events. CONCLUSIONS: Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.

Possible parachordoma in a dog.

CASE HISTORY: A 15-mm diameter mass developed in the S/C tissue overlying the right lateral gluteal muscle of a 6(1/2)-year-old female Flat-coated Retriever. PATHOLOGICAL FINDINGS: Cytological preparations following aspiration of the mass were highly cellular and consisted of a population of large polygonal cells containing single to multiple nuclei, large prominent nucleoli, and intracytoplasmic vacuoles. Histologically, the neoplasm consisted of similar large cells surrounded by thick fibrous connective tissue trabeculae. The large polygonal cells reacted positively with antibodies against vimentin, low- and high-molecular-weight variants of cytokeratin (AE1/AE3), but not with antibodies to desmin or glial fibrillary acidic protein (GFAP). DIAGNOSIS: The clinical, gross, histological and immunohistochemical findings are similar to those reported for parachordomas in humans. Neither recurrence nor metastases were noted 18 months after surgical excision of the mass. CLINICAL RELEVANCE: This is the first reported case of a possible parachordoma in a dog, a benign tumour with cytological features of malignancy.

Would offering rapid point-of-care testing or non-invasive methods improve uptake of HIV testing among high-risk genitourinary medicine clinic attendees? A patient perspective.

While most genitourinary (GU) medicine clinics achieve a high uptake for testing HIV in new patients, they may still miss testing those at highest risk. Point-of-care testing (POCT) and salivary samples are acceptable and feasible but have not yet been shown to increase uptake among high-risk patients (HRP). This study aimed to describe reasons why HRP decline HIV testing and whether offering POCT along with standard testing would increase the uptake of testing HIV in two London GU medicine clinics. Anonymous self-administered questionnaires were offered to all new and rebooked patients. Eight hundred and ninety-nine questionnaires were analysed of which 598 were HRP. Uptake of HIV testing was 77.1% among HRP and 65.8% among the rest. A total of 51.1% of HRP who declined HIV testing said they would be more likely to accept a POCT and 32.8% a salivary test. Introduction of rapid POCT for HIV would increase patient's choice and may increase the likelihood of HRP accepting an HIV test.

Acute B-cell lymphoblastic leukaemia in a 5-month-old boar.

CASE HISTORY: A 5-month-old mixed-breed boar presented with lethargy, weakness and anorexia of 1 week's duration. CLINICAL FINDINGS AND DIAGNOSIS: The boar had an elevated heart rate, slow capillary refill time and cyanotic skin over the ears; it was also severely anaemic. A necropsy revealed scattered petechial haemorrhages, small subcapsular white nodules on the kidneys, a nodule in the parenchyma of one testis, creamy-white bone marrow, a preputial diverticulum, and an ulcer of the pars oesophagea of the stomach. Cytology of peripheral blood and bone marrow identified large numbers of lymphoblasts, which were demonstrated using immunocytochemistry to be of B-cell origin. Histological examination of multiple organs also showed lymphoblastic infiltration. DIAGNOSIS: B-cell lymphoblastic leukaemia with secondary infiltration of lymphoid organs, kidneys, testis and preputial skin. CLINICAL RELEVANCE: This is the fi rst known reported case of acute B-cell lymphoblastic leukaemia in swine.

Possible pseudogout in two dogs.

Pseudogout, the acute form of calcium pyrophosphate deposition disease, is a common condition in elderly human beings and is characterised by the sudden onset of intense joint pain and synovitis. It is rarely identified in animals but was diagnosed in two dogs that presented with acute lameness and pyrexia. Cytology of the synovial fluid showed a mildly elevated cell count with both non-degenerate neutrophils and mononuclear cells present. Many of the mononuclear cells and occasional neutrophils contained square or rhomboid-shaped crystals that were variable in shape and size and weakly birefringent on examination under polarised light. Clinical signs resolved following treatment with prednisolone.

The effect on creatinine kinase activity of freezing plasma from healthy foals.

AIM: To assess the stability of creatine kinase (CK) activity in plasma collected from healthy foals and frozen at -20 degrees C for up to 12 weeks. METHODS: Samples of venous blood drawn from 25 foals were analysed for CK activity soon after collection, and again after 1 and 12 weeks of freezing at -20 degrees C. RESULTS: CK activity decreased (p<0.001) between Week 0 and Week 1 and between Week 0 and Week 12. CONCLUSIONS AND CLINICAL RELEVANCE: Decreases in CK activity were statistically significant but clinically insignificant.

The use of therapeutic drug monitoring in the management of protease inhibitor-related toxicity.

The aim of this project was to determine whether therapeutic drug monitoring (TDM) and subsequent dose modification is effective in the management of protease inhibitor (PI)-associated toxicity. A retrospective case-notes review of patients who had had TDM for suspected antiretroviral drug toxicity from November 2000 to March 2002 was carried out. This identified six symptomatic patients in whom high plasma drug levels of a PI had been found and subsequent dose modification was associated with improvement/resolution of symptoms. In 5/6 patients viral loads were below the level of detection prior to TDM and remained so after dose reduction of PI. TDM-directed dose modification of PI enables patients to continue effective regimens of highly active antiretroviral therapy, thus avoiding the need to switch the regimen.

Finite element modelling of ultrasound, with reference to transducers and AE waves.

Finite element (FE) modelling has a role to play in simulating elastic wave propagation associated with structural vibrations, acoustic phenomena and ultrasound problems. In this work we have used the PAFEC software [PAFEC finite element software PACSYS, Strelley Hall, Nottingham, NG8 6PE, UK]. With the advent of increased computer power and greater availability of software these simulations have become more readily available and will provide improved insight into wave propagation problems. Simulations have been undertaken of transient wave propagation in steel plates with an attached simple resonant transducer. This simulates acoustic emission (AE) propagation in plate like structures relevant to many industrial applications. Simulations for short propagation distances suggest the resonant transducer voltage signal carries information on the plate-waves propagating in the structure, overlaid with the piezoelectric resonance and some information might be extracted from the transducer signal. Looking at the wave propagation information alone, a great deal of variability is seen in the displacement profile for different source types, orientations and locations. Although users have expressed a need for calibration of the AE detection process, this idea remains problematic since the complete generation and detection system has the features of a chaotic system. Using FE modelling a method of "point calibration" might be available, for some specific AE applications such as crack growth along known paths.

Geochemical evidence for atmospheric pollution derived from prehistoric copper mining at Copa Hill, Cwmystwyth, mid-Wales, UK.

This paper presents geochemical data from a blanket peat located close to a Bronze Age copper mine on the northern slopes of the Ystwyth valley, Ceredigion, mid-Wales, UK. The research objective was to explore the possibility that the peat contained a geochemical record of the pollution generateD by mining activity. Four peat monoliths were extracted from the blanket peat to reconstruct the pollution history of the prehistoric mine. Three different geochemical measurement techniques were employed and four copper profiles have been reconstructed, two of which are radiocarbon-dated. The radiocarbon dates at one profile located close to the mine confirm that copper enrichment occurs in the peat during the known period of prehistoric mining. Similar enrichment of copper concentrations is shown in one adjacent profile and a profile within 30 m away. In contrast, copper was not enriched in the other radiocarbon-dated monolith, collected approximately 1.35 km to the north of the mine. Whilst other possible explanations to explain the copper concentrations are discussed, it is argued that the high copper concentrations represent evidence of localised atmospheric pollution caused by Bronze Age copper mining in the British Isles. The results of this study suggest that copper may be immobile in blanket peat and such deposits can usefully be used to reconstruct atmospheric pollution histories in former copper mining areas.

Rattling the plate--reasons and rationales for early weaning.

To identify a range of attitudes and beliefs which influence the timing of introduction to solid food, five focus group discussions were undertaken within a maternity hospital setting. These sessions explored early feeding behaviour, stimuli to changing feeding habits and subsequent responses in 22 primiparous and seven multiparous mothers (mean age 27.0+/-4.8 years) with babies aged 8-18 weeks (mean age 13.0+/-4.2 weeks). One-third of the participants had introduced solid food to their infants (mean age of introduction 11.6 weeks, range 2-16 weeks). Mothers believed that the introduction of solids was baby led and initiated by some physical characteristic or behavioural action of the infant. All mothers were aware of current recommendations to avoid the introduction of solid food until 4 months. Few knew why this should be and concepts of long-term ill health were difficult to conceptualize. The conflict between rigid feeding guidelines and flexible advice from supportive health professionals created confusion over the importance of good weaning practices. The current findings highlight issues relevant to the introduction of solid food, and provide a foundation for further research which can identify the relative importance of these factors and provide a rationale for the design of contemporary intervention strategies.