Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy.

PURPOSE: H3K27M- and H3G34R-mutant gliomas are recently-classified subgroups of high-grade gliomas (HGGs) affecting younger adults. This study aimed to describe patterns of infiltration and failure, and the volumetric response of these tumours to radiotherapy. METHODS: Patients with histone-mutant gliomas aged 16-50 years, managed from 2009 to 2021 were identified and clinical, radiological and histopathological characteristics collected. Tumour volume was assessed on MRI at diagnosis, pre-radiotherapy, month + 1, + 3 and + 5 post-radiation and at relapse. RESULTS: Of 538 IDH1/2 wild-type HGGs, 18(15%) had a histone alteration. Eleven were H3K27M- and 7 H3G34R-mutant respectively. Median age at diagnosis was 20 years (range17-48 years). Median overall survival was 20 months (95%CI 14-29 months). Both H3K27M- and H3G34R-mutant tumours exhibited extensive T2F infiltration involving a median of 4 neuroanatomical subsites at diagnosis. Median volume of disease pre-radiotherapy on T1gd and T2F respectively was 0.5cm3 (IQR:0-1.7cm3) and 11.9 cm3 (IQR:7.5-29.6cm3) for H3K27M and 0.9cm3 (IQR:0-8.4cm3) and 43.8cm3 (IQR:25.2-86.6 cm3) for H3G34R tumours. T2F volume reduction > 50% was observed 3-months post-IMRT in 7(64%) patients with H3K27M and 1(14%) with H3G34R tumours. Fourteen patients had relapsed. Relapse was local-only, distant-only and both in 4(44%), 3(33%) and 2(22%) H3K27M-mutant and 1(20%), 2(40%), and 2(40%) H3G34R-mutant tumours. On last scan before death, leptomeningeal spread was present in 4/8(50%) and 1/5(20%) and subependymal spread in 4/8 (50%) and 0/5 H3K27M- and G34R-mutant cases respectively. CONCLUSION: H3K27M-mutant gliomas are highly responsive to radiotherapy but exhibit high propensity for subsequent leptomeningeal and subependymal spread. H3G34R-mutant tumours exhibit lesser early volumetric response to radiotherapy and propensity for distant in-brain failure.

Outcomes from the use of computerized neurocognitive testing in a recurrent glioblastoma clinical trial.

Assessment of neurocognitive function (NCF) is important in brain tumor clinical trials, however there are varying methodologies available. We used the Cogstate computerized NCF testing battery and the mini-mental state examination (MMSE) to prospectively assess cognition in adult patients with recurrent glioblastoma (GBM) enrolled in the CABARET randomized phase II clinical trial of bevacizumab versus bevacizumab plus carboplatin chemotherapy. We determined completion rates; compared NCF results between trial arms; and assessed baseline NCF as a predictor of survival outcome. 93 of 103 eligible patients completed baseline Cogstate NCF testing. Completion rates were between 60 and 100% across each timepoint, and 38% at disease progression. There was no evidence of difference between arms in time to deterioration in NCF using either test. Prior to disease progression, deterioration on the Cogstate tests was substantially more common (90%) than deterioration on the MMSE (37%), and decline in the Cogstate composite score within the first 8 weeks was associated with shorter overall survival. This testing methodology may be useful when determining net clinical benefit for therapies in patients with recurrent GBM.

A Review of the Challenge-Hindrance Stress Model: Recent Advances, Expanded Paradigms, and Recommendations for Future Research.

Since its introduction approximately 20 years ago, the Challenge-Hindrance Stress Model (CHM) has been widely accepted both among academic and practitioner audiences. The model posits that workplace stressors can be grouped into two categories. Hindrance stressors will interfere with performance or goals, while challenge stressors contribute to performance opportunities. These two categories of stressors are theorized to exhibit differential relationships with strain, with hindrance stressors being more consistently linked to psychological, physical, or behavioral strain compared to challenge stressors. Despite the popularity of this model, recent evidence suggests that the proposed differential relationship hypothesis has not consistently held true for all types of strain. Thus, a reexamination or modification of this paradigm is clearly warranted. In the present review, we describe existing evidence surrounding the CHM and describe the rationale for a shifting paradigm. We outline recent advances in research using the CHM, such as novel moderators and mediators, the need to explicitly measure challenge and hindrance appraisal and differentiate between hindrance and threat appraisal, the dynamic nature of these appraisals over time, and the recognition that a single stressor could be appraised simultaneously as both a challenge and a hindrance. Finally, we provide recommendations and future research directions for scholars examining stress and stress management through a CHM lens, including recommendations related to study design, the measurement of stressors, the integration of CHM with other models of stress, and interventions for stress management.

Pattern of failure in anaplastic glioma patients with an IDH1/2 mutation.

PURPOSE: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. METHODS: The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. RESULTS: A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6­year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (p < 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, p = 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (p < 0.002) and delayed IMRT until the second relapse (p < 0.001). CONCLUSION: Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.

Understanding the Revised Fourth Edition of the World Health Organization Classification of Tumours of the Central Nervous System (2016) for Clinical Decision-making: A Guide for Oncologists Managing Patients with Glioma.

The recognition of specific molecular prognostic factors has altered the management of primary brain tumours over the past decade. These factors have allowed stratification of morphologically similar tumours into different prognostic groups and are now also being used to determine clinical trial eligibility. Many of these factors have been included in the revised fourth edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System, released in May 2016. This revised edition places greater emphasis on molecular testing and, for certain tumour types, molecular testing is required for diagnosis. Many pathology departments have also adopted the four-tiered report format suggested in the Haarlem guidelines, and provide a final 'integrated diagnosis' incorporating a morphological diagnosis, the WHO grade and molecular findings. Pathologists need to perform and report these molecular tests in a timeframe that is relevant for clinical decision-making. Clinicians need to understand and incorporate these changes into their daily practice, as they have direct effects on both the type and intent of therapeutic interventions.

Reducing radiation dose to normal brain through a risk adapted dose reduction protocol for patients with favourable subtype anaplastic glioma.

AIM: In patients with isocitrate dehydrogenase (IDH) mutated anaplastic glioma determine the dosimetric benefits of delivering radiation therapy using a PET guided integrated boost IMRT technique (ib-IMRT) compared with standard IMRT (s-IMRT) in reducing dose to normal brain. METHODS: Ten patients with anaplastic glioma, identified as a favourable molecular subgroup through presence of IDH mutation, and managed with radiation therapy using an ib-IMRT were enrolled into a dosimetric study comparing two RT techniques: s-IMRT to 59.4Gy or ib-IMRT with 59.4/54Gy regions. Gross Tumour volume (GTV) and Clinical Target Volumes (CTV) were determined by MRI, 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET imaging. A standard risk Planning Target Volume (PTVsr) receiving 59.4Gy (PTV59.4) in the s-IMRT technique was determined by MRI T2Flair and FET PET. For the ib-IMRT technique this PTVsr volume was treated to 54Gy, and the high-risk PTV (PTVhr) receiving 59.4Gy was determined as a higher risk region by FDG PET and MRI gadolinium enhancement. Standard dosimetric criteria and normal tissue constraints based on recent clinical trials were used in target delineation and planning. Normal Brain was defined as Brain minus CTV. Endpoints for dosimetric evaluation related to mean Brain dose (mBrainDose), brain volume receiving 40Gy (Brainv40) and 20Gy (Brainv20). The variation between the dosimetric endpoints for both techniques was examined using Wilcoxon analysis. RESULTS: The 10 patients had tumours located in temporal (1), parietal (3), occipital (2) and bifrontal (4) regions. In ib-IMRT technique the median volume of PTVhr was 25.5 cm3 compared with PTVsr of 300.0 cm3. For dose to PTVhr the two treatments were equivalent (p = 0.33), and although the ibIMRT had a prescribed 10% dose reduction from 59.4Gy to 54Gy the median reduction was only 5.9%. The ib-IMRT dosimetry was significantly improved in normal brain endpoints specifically mBrainDose (p = 0.007), Brainv40 (p = 0.005) and Brainv20 (p = 0.001), with a median reduction of 9.3%, 19.0 and 10.8% respectively. After a median follow-up of 38 months two patients have progressed, with no isolated relapse in the dose reduction region. CONCLUSION: An approach using ib-IMRT for anaplastic glioma produces significant dosimetric advantages in relation to normal brain dose compared with s-IMRT plan. This is achieved without a significant reduction to the target volume dose despite the reduction in prescribed dose. This technique has advantages to minimise potential late neurocognitive effects from high dose radiation in patients with favorable subtype anaplastic glioma with predicted median survival beyond ten years.

Radiotherapy in Glioblastoma: the Past, the Present and the Future.

The aim of this review is to explore the changing utility of radiotherapy in the treatment of patients with glioblastoma over the past 60 years. Together with surgery, radiotherapy has always been the cornerstone of treatment of glioblastoma, but techniques have significantly advanced over this time. The exploration of early two-dimensional techniques, investigation of dose escalation, concomitant chemotherapy and modern techniques, including intensity-modulated radiotherapy, image-guided radiotherapy, and volumetric-modulated arc therapy will be covered. In addition, current controversies including decreasing margin size, re-irradiation, treatment of elderly patients, and novel imaging tracers will be discussed. Future directions including immunotherapy and tumour treating fields are examined. Radiotherapy-based treatments cannot rely solely on advances in chemotherapy or immunotherapy to improve the overall survival of patients with glioblastoma. Radiation oncology needs to continue to develop and improve the delivery, target definition, and dose of radiotherapy to these patients to improve their survival and the toxicity associated with treatment.

Proliferation Index Predicts Survival after Second Craniotomy within 6 Months of Adjuvant Radiotherapy for High-grade Glioma.

AIMS: To determine pathological features that predict survival in patients having repeat craniotomy within 6 months of radiotherapy for high-grade glioma (HGG). MATERIALS AND METHODS: HGG patients (World Health Organization grade 3/4) managed with repeat craniotomy within 6 months of completing radiotherapy between 2008 and 2012 were included. Based on the presence of residual tumour cells, the pathology was reported as pathological progression or pathological pseudoprogression. The proliferation index (Ki67) was reported and compared with initial pathology as a percentage change. Tumour necrosis was estimated as a percentage of the specimen. Overall survival was calculated in months. RESULTS: Of 327 patients managed with HGG, 27 patients underwent repeat craniotomy within 6 months of radiotherapy. The median survival after reoperation was 11 months (95% confidence interval 1-22). Ki67 at reoperation of 0%, 1-9% and >10% was associated with survival with a median survival of 13, 13 and 3 months, respectively (P = 0.007). Change in Ki67 was also associated with median survival, with <50% reduction median survival 3 months, 50-80% median survival 7 months and >80% reduction median survival 13 months, P = 0.02. Widespread treatment-related necrosis improved outcome, with >80% necrosis having a median survival of 13 months versus 3 months in those with <80% necrosis (P = 0.003). CONCLUSION: The presence of residual tumour at repeat craniotomy within 6 months of radiotherapy is not an independent indicator of prognosis. Patients with residual tumour that had a low Ki67 had a similar median survival as those with only treatment necrosis. Reduced proliferation of residual tumour cells and widespread necrosis may be more important indicators for future outcome.

How will the greening of the Arctic affect an important prey species and disturbance agent? Vegetation effects on arctic ground squirrels.

Increases in terrestrial primary productivity across the Arctic and northern alpine ecosystems are leading to altered vegetation composition and stature. Changes in vegetation stature may affect predator-prey interactions via changes in the prey's ability to detect predators, changes in predation pressure, predator identity and predator foraging strategy. Changes in productivity and vegetation composition may also affect herbivores via effects on forage availability and quality. We investigated if height-dependent effects of forage and non-forage vegetation determine burrowing extent and activity of arctic ground squirrels (Urocitellus parryii). We collected data on burrow networks and activity of arctic ground squirrels across long-term vegetation monitoring sites in Denali National Park and Preserve, Alaska. The implications of height-specific cover of potential forage and non-forage vegetation on burrowing behaviour and habitat suitability for arctic ground squirrels were investigated using hierarchical Bayesian modelling. Increased cover of forbs was associated with more burrows and burrow systems, and higher activity of systems, for all forb heights. No other potential forage functional group was related to burrow distribution and activity. In contrast, height-dependent negative effects of non-forage vegetation were observed, with cover over 50-cm height negatively affecting the number of burrows, systems and system activity. Our results demonstrate that increases in vegetation productivity have dual, potentially counteracting effects on arctic ground squirrels via changes in forage and vegetation stature. Importantly, increases in tall-growing woody vegetation (shrubs and trees) have clear negative effects, whereas increases in forb should benefit arctic ground squirrels.

Elderly patients aged 65-75 years with glioblastoma multiforme may benefit from long course radiation therapy with temozolomide.

To determine the outcome of elderly patients with glioblastoma managed with hypofractionated [40 Gray (Gy)] or long-course (60 Gy) radiation therapy (RT). Patients aged >60 years diagnosed with WHO grade IV glioma managed with RT between October 2006 and July 2012 were retrospectively identified. Baseline data including ECOG performance status, RT dose and use of temozolomide (TMZ) were recorded. Overall survival was calculated in months from date of diagnosis. 109 patients were included with age distribution from 61 to 88 years (13 % <65, 63 % 65-75, and 24 % >75). Median survival (MS) of total group was 12 months (95 % CI 11-13) with 12 % surviving beyond 2 years. For age groups <65, 65-75, >75 the survival was 17, 12, and 9 months respectively (p = 0.001). Near total resection (p = 0.027), but not ECOG 0-1 (p = 0.34) was associated with improved MS. For the 69 patients aged 65-75, 55 % were managed with 40 Gy and 45 % 60 Gy. Longer survival was associated with the use of 60 Gy (15 vs. 9 months, p < 0.0001), and use of TMZ (13 vs. 7 months, p < 0.0001). In the 48 patients (70 %) managed with TMZ, the MS was 15 months with 60 Gy (95 % CI 13-17) compared with 11 months (95 % CI 9-13) in those with 40 Gy. Performance status with ECOG 0-1 was not associated with improved survival (p = 0.25). Within the limitations of a retrospective study, we demonstrate improved MS in the elderly population when TMZ is added to RT. Those in the age group 65-75 may benefit from long-course RT with TMZ.

Employment following chemoradiotherapy in glioblastoma: a prospective case series.

PURPOSE: Radiotherapy (RT) and temozolomide (TMZ) for glioblastoma (GBM) has resulted in longer survival. Uncertainties exist regarding quality of survival. This study aims to determine the rate of patients returning to previous employment (EM) following treatment. METHODS: Eligible patients were diagnosed with GBM, aged 18-70 years, and treated with intensity-modulated radiotherapy to 60 Gray and TMZ (EORTC Protocol) between July 2007 and July 2011. EM was defined as paid work. Exclusion criteria included patients without histological confirmation of WHO grade IV glioblastoma, those not in paid employment in the 2-month period prior to diagnosis, or mothers of pre-school aged children not working. Data were collected on EM prior (EM pre) and after RT at 6 and 12 months (EM 6 m, EM 12 m). Rate of EM was analysed in regards to baseline performance status (ECOG), neurological deficits (MRC scale) and median survival. RESULTS: One hundred twelve patients were identified with median follow-up of 15.5 months and median survival 18 months (95%CI, 15-21 months). Seventy-one patients were working prior to diagnosis and eligible for analysis. Twenty patients returned to work (28 %) by EM 6 months and 19 patients (27 %) by EM 12 months. EM 6 months was strongly associated with ECOG and MRC status, with only 1 of 37 patients (3 %) with neurological deficit returning to work compared with 21 of 36 (58 %) intact patients. Of good performance status patients not returning to work, factors included presence of income insurance, family financial support or treatment-related symptoms. CONCLUSION: A modest proportion of patients with GBM return back to work at 6 and 12 months following radiotherapy with the majority demonstrating the lowest level of neurological deficit prior to RT. IMPLICATIONS FOR CANCER SURVIVORS: Return to work following treatment does occur but it is not a common outcome.

The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients.

Clinical studies in patients with newly diagnosed glioblastoma treated with temozolomide have shown that the methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is both predictive and prognostic of outcome. Methylation of the promoter region of MGMT is the most clinically relevant measure of MGMT expression and its assessment has become integral in current and planned clinical trials in glioblastoma. Our study confirmed that MGMT methylation, assessed by pyrosequencing, is associated with a significant survival benefit in glioblastoma patients treated with temozolomide (either concurrently with radiotherapy or sequential treatment). More interestingly, our study demonstrated that a promoter variant, the c.-56C>T (rs16906252) single nucleotide polymorphism (SNP) located within a cis-acting enhancer element at the proximal end of MGMT, is associated with the presence of MGMT promoter methylation in de novo glioblastoma. Furthermore, we show that the overall survival of patients carrying both the SNP and MGMT methylation showed a strong survival benefit when compared to either molecular event on their own. Promoter reporter experiments in MGMT methylated glioblastoma cell lines showed the T allele conferred a ∼30% reduction in normalised MGMT promoter activity compared to the wild-type haplotype. This might account for the propensity of the T allele to undergo promoter methylation, and in turn, the improved survival observed in carriers of the T allele. An independent validation on larger cohorts is required to confirm the prognostic and predictive value of individuals carrying the T allele.

Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations.

Platinating agents are used in the treatment of many cancers, yet they can induce toxicities and resistance that limit their utility. Using previously published and additional world population panels of diverse ancestry totaling 608 lymphoblastoid cell lines (LCLs), we performed meta-analyses of over 3 million single-nucleotide polymorphisms (SNPs) for both carboplatin- and cisplatin-induced cytotoxicity. The most significant SNP in the carboplatin meta-analysis is located in an intron of NBAS (neuroblastoma amplified sequence; P=5.1 × 10(-7)). The most significant SNP in the cisplatin meta-analysis is upstream of KRT16P2 (P=5.8 × 10(-7)). We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Most of the variants that associate with platinum-induced cytotoxicity are polymorphic across multiple world populations; therefore, they could be tested in follow-up studies in diverse clinical populations. Seven genes previously implicated in platinating agent response, including BCL2 (B-cell CLL/lymphoma 2), GSTM1 (glutathione S-transferase mu 1), GSTT1, ERCC2 and ERCC6, were also implicated in our meta-analyses.

Clinical translation of cell-based pharmacogenomic discovery.

The use of cell-based models has emerged as a promising means to discover and validate pharmacologic phenotype-genotype relationships. The availability of large-scale genome studies in both human and model systems is now allowing us an unprecedented opportunity to understand how well cell-based models identify clinically relevant genetic variants associated with drug response and toxicity. Here we review these studies and the emerging translational information.

Liver transplantation in a randomized controlled trial of emergency treatment of acutely bleeding esophageal varices in cirrhosis.

BACKGROUND: Bleeding esophageal varices (BEV) in cirrhosis has been considered an indication for liver transplantation (LT). This issue was examined in a randomized controlled trial (RCT) of unselected, consecutive patients with advanced cirrhosis and BEV that compared endoscopic sclerotherapy (EST; n = 106) to emergency direct portacaval shunt (EPCS; n = 105). METHODS: Diagnostic work-up and treatment were initiated within 8 hours. Patients were evaluated for LT on admission and repeatedly thereafter; 96% underwent over 10 years of regular follow-up. The analysis was supplemented by 1300 unrandomized cirrhotic patients who previously underwent portacaval shunt (PCS) with 100% follow-up. RESULTS: In the RCT long-term bleeding control was 100% following EPCS, only 20% following EST. Also, 3-, 5-, 10-, and 15-year survival rates were 75%, 73%, 46%, and 46%, respectively, following EPCS compared with 44%, 21%, 9%, and 9% following EST, respectively (P < .001). Only 13 RCT patients (6%) were ultimately referred for LT mainly because of progressive liver failure; only 7 (3%) were approved for LT and only 4 (2%) underwent LT. The 1- and 5-year LT survival rates were 0.68% and 0, respectively, compared with 81% and 73%, respectively, after EPCS. In the 1300 unrandomized PCS patients, 50 (3.8%) were referred and 19 (1.5%) underwent LT. The 5-year survival rate was 53% compared with 72% for all 1300 patients. CONCLUSIONS: If bleeding is permanently controlled, as occurred invariably following EPCS, cirrhotic patients with BEV seldom require LT. PCS is effective first-line and long-term treatment. Should LT be required in patients with PCS, although technically more demanding, numerous studies have shown that PCS does not increase mortality or complications. EST is not effective emergency or long-term therapy.

Teamwork on inpatient medical units: assessing attitudes and barriers.

BACKGROUND: Discrepant attitudes about teamwork among nurses and physicians exist in operating rooms and intensive care units. Little is known about teamwork attitudes on general medical services. OBJECTIVE: To assess ratings of teamwork by providers on inpatient medical units and barriers to collaboration. DESIGN AND PARTICIPANTS: Nurses, primary hospital physicians and medical subspeciality consultants on four general medical units were surveyed. MEASUREMENTS: Providers rated the quality of communication and collaboration experienced with their own and other disciplines. Providers also rated potential barriers to collaboration. Differences between providers in ratings of collaboration and barriers were tested using analysis of variance. RESULTS: Of 230 eligible providers, 159 (69%) completed the survey. Teamwork ratings of nurses were similarly high across provider types. Ratings of physicians differed considerably by provider type (p

Phylogeography of lions (Panthera leo ssp.) reveals three distinct taxa and a late Pleistocene reduction in genetic diversity.

Lions were the most widespread carnivores in the late Pleistocene, ranging from southern Africa to the southern USA, but little is known about the evolutionary relationships among these Pleistocene populations or the dynamics that led to their extinction. Using ancient DNA techniques, we obtained mitochondrial sequences from 52 individuals sampled across the present and former range of lions. Phylogenetic analysis revealed three distinct clusters: (i) modern lions, Panthera leo; (ii) extinct Pleistocene cave lions, which formed a homogeneous population extending from Europe across Beringia (Siberia, Alaska and western Canada); and (iii) extinct American lions, which formed a separate population south of the Pleistocene ice sheets. The American lion appears to have become genetically isolated around 340 000 years ago, despite the apparent lack of significant barriers to gene flow with Beringian populations through much of the late Pleistocene. We found potential evidence of a severe population bottleneck in the cave lion during the previous interstadial, sometime after 48 000 years, adding to evidence from bison, mammoths, horses and brown bears that megafaunal populations underwent major genetic alterations throughout the last interstadial, potentially presaging the processes involved in the subsequent end-Pleistocene mass extinctions.

Rationalization of microscopy in the detection of Neisseria gonorrhoeae in women.

This study looks at the sensitivity of microscopy in the diagnosis of Neisseria gonorrhoeae (NG), the effect of microscopy on time to treatment of NG and the added value of microscopy in the management of gonorrhoea. Women diagnosed with NG at an inner city genitourinary (GU) medicine clinic between August 2005 and July 2006 were identified and the notes reviewed. There were 103 women who were culture positive for NG. The sensitivity of microscopy was 38%. Microscopy is a point of care test (POCT) and in this group, it facilitated the treatment of 19% (n=20) of cases of NG infection at the first visit to a GU medicine service. If a POCT is not available, this would result in delayed treatment (32% of patients waited longer than 14 days and 3% did not return for treatment). In total, 29% of women did not return for test of cure, therefore confirming that effective first-line therapy is essential in the treatment of N. gonorrhoeae.

A review of high frequency oscillation ventilation in the neonate.

In this study the use of high frequency oscillation (HFO) to treat neonates with respiratory failure is analysed. The theories behind gas exchange during HFO are reviewed and its specific application to neonatal care discussed. The mechanical performance of three HFO ventilators currently in use is compared with the views of medical staff operating them on a regular basis. The complex interactions between initial ventilator settings have led to difficulties in accurately comparing performance characteristics and ventilation strategies; each ventilator is seen to have its own strengths and weaknesses that contribute to the ventilator selection made. These interactions together with the specific HFO modes available on each ventilator should be taken into account when using a HFO for the first time or when switching from an alternative ventilation method. Medical staff who care for neonates suggest staff education and training into the variations of HFO will greatly improve its use in neonatal medicine.

Management of a syphilis outbreak in street sex workers in east London.

OBJECTIVE: To describe the control and management of a syphilis outbreak in female street sex workers (SSWs) in east London. METHODS: Following the identification of several cases of infectious syphilis in SSWs in east London, a targeted service for screening and treatment of syphilis and other sexually transmitted infections was developed. A multidisciplinary team (MDT) joined an existing outreach service to facilitate this. Once it became apparent that this was not an isolated case, an outbreak control team (OCT) was established. RESULTS: Between April and December 2004 a total of 14 (58%) women with 15 cases of infectious syphilis were identified in 24 SSWs: 14/15 (93%) received treatment. Epidemiological treatment for syphilis was also given to the rest of SSWs at the initial visit. Several coexistent STIs were identified in this cohort. As part of the enhanced outbreak surveillance in north east London, 21 cases of infectious syphilis were reported in SSWs between April 2004 and December 2005. CONCLUSION: Outbreak management in this population was challenging: an MDT approach was crucial in identifying and treating syphilis to prevent onward transmission. There was a high prevalence of syphilis and other STIs in this cohort, and we treated the majority of cases. The formation of an OCT enabled us to monitor the outbreak and implement control measures more effectively. The novel intervention we describe has proved valuable in helping to control this syphilis outbreak.