Risk of persistent or recurrent cervical neoplasia in patients with 'pure' adenocarcinoma-in-situ (AIS) or mixed AIS and high-grade cervical squamous neoplasia (cervical intra-epithelial neoplasia grades 2 and 3 (CIN 2/3)): a population-based study.

OBJECTIVE: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma. DESIGN: Retrospective cohort study. SETTING: Statewide population in Western Australia. POPULATION: Women diagnosed with AIS between 2001 and 2012. METHODS: We conducted a retrospective, population-based cohort study. MAIN OUTCOME MEASURES: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma. RESULTS: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence. CONCLUSION: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease. TWEETABLE ABSTRACT: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3.

The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two-centre observational study.

OBJECTIVE: To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: A total of 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. METHODS: Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi-square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features. MAIN OUTCOME MEASURES: Colposcopic features, HPV genotypes, mRNA expression, and cervical histology. RESULTS: The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated). CONCLUSIONS: In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines. TWEETABLE ABSTRACT: Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.

The enigma of neurogenic thoracic outlet syndrome following motor vehicle collisions.

BACKGROUND: The concept of neurogenic thoracic outlet syndrome (N-TOS) including upper and lower plexus syndromes secondary to soft tissue neck injury after motor vehicle collisions (MVCs) has been contentious. We considered that analysis of objective data from this group of patients could provide insight into this controversial type of N-TOS. METHODS: During the 10-year period January 2001 through December 2010 we examined patients who had received a diagnosis of N-TOS following an MVC. We graded the principal diagnosis based on the objective data from our physical examination. RESULTS: In total 263 patients received a diagnosis of N-TOS during the study period. At the highest accuracy level of diagnosis there were 56 patients with ulnar entrapment syndrome (UES), 40 with carpal tunnel syndrome (CTS) and 55 with nonorganic disease (NOD), for a total of 151 (57.4%) cases in which the diagnosis of N-TOS was brought into question. The elevated arm stress test (EAST) reproduced the symptoms of UES in 33 of the 56 patients of UES (58.9%) and reproduced the symptoms of CTS in 18 of the 40 patients with CTS (45.0%). CONCLUSION: There appears to be a high incidence of misdiagnosis of N-TOS following MVCs. The EAST is not a prime test for N-TOS.

BACKGROUND: Il n'y a pas consensus sur le concept de syndrome du défilé thoraco-brachial (SDTB) neurogène comprenant des syndromes du plexus brachial inférieur et supérieur consécutifs à une blessure aux tissus mous du cou découlant d'une collision de véhicules motorisés. Nous avons pensé que l'analyse de données objectives sur les patients touchés pourrait aider à comprendre ce type controversé de SDTB neurogène. METHODS: Durant une période de 10 ans, soit de janvier 2001 à décembre 2010, nous avons examiné des patients ayant reçu un diagnostic de SDTB neurogène après une collision de véhicules motorisés. Nous avons coté le diagnostic principal selon les données objectives de notre examen physique. RESULTS: Au total, 263 patients ont reçu un diagnostic de SDTB neurogène durant la période à l'étude. Au degré le plus précis de diagnostic, 56 patients étaient atteints de syndrome canalaire du nerf cubital, 40, de syndrome du canal carpien et 55, de maladies non organiques, pour un total de 151 patients, ou 57,4 % des cas pour lesquels le diagnostic de SDTB neurogène avait été envisagé. La manoeuvre du chandelier (test de Roos) a reproduit les symptômes du syndrome canalaire du nerf cubital chez 33 des 56 patients atteints (58,9 %) et ceux du syndrome du canal carpien chez 18 des 40 patients atteints (45,0 %). CONCLUSION: Il semble y avoir une forte incidence de mauvais diagnostics de SDTB neurogène après des collisions de véhicules motorisés. Le test de Roos n'est pas un test de premier choix pour ce syndrome.

MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms.

BACKGROUND: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients. METHODS: We used TaqMan low-density array (TLDA) qRT-PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion. RESULTS: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial-mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells. CONCLUSIONS: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers.

Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?

OBJECTIVE: To compare the outcomes of patients with cervical adenocarcinoma in situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ (ACIS). STUDY DESIGN: This is a retrospective, population-based cohort study of Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes included pathological margin status and the incidence of persistent or recurrent endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The study group comprised 338 patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow-up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%) patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with adenocarcinoma during the follow-up and surveillance periods. No patient died of cervical cancer within the study period. There were no significant differences in the incidence of persistent and/or recurrent endocervical neoplasia according to the type of excisional procedure. Patients with positive biopsy margins were 3.4 times more likely to have disease persistence or recurrence. CONCLUSION(S): LEEP and CKC biopsy appear equally effective in the treatment of ACIS for women wishing to preserve fertility. Patients undergoing conservative management for ACIS should be closely monitored, particularly if biopsy margins are positive in initial excision specimens. Patients and their clinicians should be aware of the potential risks of residual and recurrent disease.

Risk of transmission associated with sharing drug injecting paraphernalia: analysis of recent hepatitis C virus (HCV) infection using cross-sectional survey data.

Sharing injecting paraphernalia (containers, filters and water) poses a risk of transmitting the hepatitis C virus (HCV). The prevalence of, and risk of HCV from, such behaviour has not been extensively reported in Europe. People who inject drugs (PWID) were recruited in cross-sectional surveys from services providing sterile injecting equipment across Scotland between 2008 and 2010. Participants completed a questionnaire and provided a blood spot for anonymous testing. Logistic regression was used to examine the association between recent HCV infection (anti-HCV negative and HCV-RNA positive) and self-reported measures of injecting equipment sharing in the 6 months preceding interview. Twelve per cent of the sample reported sharing needles/syringes, and 40% reported sharing paraphernalia in the previous 6 months. The adjusted odds ratios (AOR) for sharing needles/syringes (+/- paraphernalia), and sharing only paraphernalia in the last 6 months were 6.7 (95% CI 2.6-17.1) and 3.0 (95% CI 1.2-7.5), respectively. Among those who reported not sharing needles/syringes, sharing containers and filters were both significantly associated with recent HCV infection (AOR 3.1, 95% CI 1.3-7.8 and 3.1, 95% CI 1.3-7.5, respectively); sharing water was not. We present the first study to apply a cross-sectional approach to the analysis of the association between sharing paraphernalia and incident HCV infection and demonstrate consistent results with previous longitudinal studies. The prevalence of paraphernalia sharing in our study population is high, representing significant potential for HCV transmission.

What is a virtual multidisciplinary team (vMDT)?

BACKGROUND: Multidisciplinary team meetings (MDTs), also known as tumour boards or multidisciplinary case conferences, are an integral component of contemporary cancer care. There are logistical problems with setting up and maintaining participation in these meetings. An ill-defined concept, the virtual MDT (vMDT), has arisen in response to these difficulties. We have, in order to provide clarity and to generate discussion, attempted to define the concept of the vMDT, outline its advantages and disadvantages, and consider some of the practical aspects involved in setting up a virtual MDT. METHODS: This is an unstructured review of published evidence and personal experience relating to virtual teams in general, and to MDTs in particular. RESULTS: We have devised a simple taxonomy for MDTs, discussed some of the practicalities involved in setting up a vMDT, and described some of the potential advantages and disadvantages associated with vMDTs. CONCLUSION: The vMDT may be useful for discussions concerning rare or unusual tumours, or for helping guide the assessment and management of patients with uncommon complications related to treatment. However, the vMDT is a niche concept and is currently unlikely to replace the more traditional face-to-face MDT in the management of common tumours at specific sites.

Chromosome instability and benefit from adjuvant anthracyclines in breast cancer.

BACKGROUND: Duplication of the centromeric region of chromosome 17 (Ch17CEP) is associated with sensitivity to anthracyclines. An explanation may be chromosome instability (CIN); a frequent event in solid tumours associated with poor outcome. The predictive value of CIN seems to be drug dependent and CIN has been associated with both sensitivity and resistance to chemotherapy. METHODS: In this study, we used fluorescent in situ hybridisation for chromosomes 1, 7, 11, 17 and 18 to identify patients with high tumour CIN% in 322 patients recruited into the BR9601 clinical trial. RESULTS: High tumour CIN% was correlated to Ch17CEP (P=3.68e-7) and is associated with a reduced RFS (P=0.0011) and OS (P=0.04). Patients with high CIN had a decreased risk of death on E-CMF compared with CMF. CONCLUSION: CIN is of prognostic significance and may be of predictive value in determining anthracycline response, although further testing is required.

Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials.

BACKGROUND: The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses. METHODS: National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles. RESULTS: In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65-0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65-0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours. CONCLUSION: Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.

Improving treatment for people with cognitive impairment and substance misuse issues: Lessons from an inclusive residential treatment program pilot in Australia.

BACKGROUND: Approximately half of the substance dependence treatment population is estimated to have a cognitive impairment, which reduces participation, retention, and post-treatment outcomes. Cognitive behaviour change approaches are less effective for this population and cognitive remediation strategies have been found to improve outcomes. Evidence on modified programs to remove environmental barriers for treatment seekers with disability does not exist. OBJECTIVE: A modified residential substance misuse treatment program in New South Wales, Australia, was piloted and evaluated to address this knowledge gap. METHOD: Of 67 residents who received treatment during the evaluation period, 33 were screened as having cognitive impairment. Twelve residents took part in an interview and 10 staff in a focus group to understand their views of the pilot program. Resident characteristics and retention rates and themes about program benefits and challenges are reported. RESULTS: Treatment completion was up to five times higher for residents with cognitive impairment after the new program was implemented. The pilot program provided simplified written and visual materials and concrete examples and introduced a daily virtues program to embed new learning and support behaviour change. Resources to allow staff to engage more intensively with residents and provision of ongoing staff training were viewed as essential for program success. CONCLUSIONS: Environmental adaptations, including a combination of conventional treatment modalities with accessible design and person-centred principles, removed barriers to treatment for residents with cognitive impairment. Creating a climate where respect, tolerance and peer support were normalised was likely to have been particularly beneficial for these residents.

Identification of N-terminal regions of wheat leaf ferredoxin NADP+ oxidoreductase important for interactions with ferredoxin.

Wheat leaves contain two isoproteins of the photosynthetic ferredoxin:NADP(+) reductase (pFNRI and pFNRII). Truncated forms of both enzymes have been detected in vivo, but only pFNRII displays N-terminal length-dependent changes in activity. To investigate the impact of N-terminal truncation on interaction with ferredoxin (Fd), recombinant pFNRII proteins, differing by deletions of up to 25 amino acids, were generated. During purification of the isoproteins found in vivo, the longer forms of pFNRII bound more strongly to a Fd affinity column than did the shorter forms, pFNRII(ISKK) and pFNRII[N-2](KKQD). Further truncation of the N-termini resulted in a pFNRII protein which failed to bind to a Fd column. Similar k(cat) values (104-140 s(-1)) for cytochrome c reduction were measured for all but the most truncated pFNRII[N-5](DEGV), which had a k(cat) of 38 s(-1). Stopped-flow kinetic studies, examining the impact of truncation on electron flow between mutant pFNRII proteins and Fd, showed there was a variation in k(obs) from 76 to 265 s(-1) dependent on the pFNRII partner. To analyze the sites which contribute to Fd binding at the pFNRII N-terminal, three mutants were generated, in which a single or double lysine residue was changed to glutamine within the in vivo N-terminal truncation region. The mutations affected binding of pFNRII to the Fd column. Based on activity measurements, the double lysine residue change resulted in a pFNRII enzyme with decreased Fd affinity. The results highlight the importance of this flexible N-terminal region of the pFNRII protein in binding the Fd partner.

Characteristics of patients dying within 30 days of diagnosis of breast or colorectal cancer in Scotland, 2003-2007.

BACKGROUND: Recent research has shown that most of the excess risk of death following breast and colorectal cancer in England compared with Norway and Sweden occurs in older age groups during the first year, and especially in the first month of follow-up. The aim of this study was to explore the characteristics of patients dying within 30 days of being diagnosed with one of these cancers in Scotland during 2003-2007. METHODS: Anonymised cancer registry records linked to hospital discharge and death records were extracted. The study population was divided into patients who died within 30 days of diagnosis (cases) and those who survived beyond this threshold (controls). Differences in patient-, tumour-, and health service-related characteristics were assessed using the χ(2)-test and logistic regression. RESULTS: Patients dying within 30 days were more likely to be elderly and to have experienced emergency admission to non-surgical specialities. Their tumours were less likely to have been verified microscopically, but they appeared more likely to be of high grade and advanced in stage. A substantial number of patients died from causes other than their cancer. CONCLUSION: These results suggest that early mortality after a diagnosis of breast or colorectal cancer may be partly due to comorbidity and lifestyle factors, as well as due to more advanced disease. Further research is required to determine the precise explanation for these findings and, in particular, if any potentially avoidable factors such as delays in presentation, referral, or diagnosis exist.

Considerations for prostheses choice in multiple valve surgery.

OBJECTIVES: The prosthesis type for multiple valve surgery (replacement of two or more diseased native or prosthetic valves, replacement of two diseased valves with repair/reconstruction of a third, or replacement of a single diseased valve with repair/reconstruction of a second valve) remains inadequately evaluated. The clinical performance of multiple valve surgery with bioprostheses (BP) and mechanical prostheses (MP) was assessed to compare patient survival and composites of valve-related complications. METHODS: Between 1975 and 2000, 1245 patients had multiple valve surgery (BP 785, mean age 62.0 ± 14.7 years; and MP 460, mean age 56.9 ± 12.9 years). There were 1712 procedures performed [BP 969(56.6%) and MP 743(43.4%). Concomitant coronary artery bypass (conCABG) was BP 206(21.3%) and MP 105(14.1%) (p = 0.0002). The cumulative follow-up was BP 5131 years and MP 3364 years. Independent predictors were determined for mortality, valve-related complications and composites of complications. RESULTS: Unadjusted patient survival at 12 years was BP 52.1 ± 2.1% and MP 54.8 ± 4.6% (p = 0.1127), while the age adjusted survival was BP 48.7 ± 2.3% and MP 54.4 ± 5.0%. The predictors of overall mortality were age [Hazard Ratio (HR) 1.051, p < 0.0001], previous valve (HR 1.366, p = 0.028) and conCABG (HR 1.27, p = 0.021). The actual freedom from valve-related mortality at 12 years was BP 85.6 ± 1.6% and MP 91.0 ± 1.6% (actuarial p = 0.0167). The predictors of valve-related mortality were valve type (BP > MP) (2.61, p = 0.001), age (HR 1.032, p = 0.0005) and previous valve (HR 12.61, p < 0.0001). The actual freedom from valve-related reoperation at 12 years was BP 60.8 ± 1.9% and MP85.6 ± 2.1% (actuarial p < 0.001). The predictors of valve-related reoperation were valve type (MP > BP) (HR 0.32, p < 0.0001), age (HR 0.99, p = 0.0001) and previous valve (HR 1.38, p = 0.008) CONCLUSIONS: Overall survival (age adjusted) is differentiated by valve type over 10 and 12 years and valve-related mortality and valve-related reoperation favours the use of mechanical prostheses, overall for multiple valve surgery.

Cooperation across the histocompatibility barrier: H2d T cells primed to antigen in an H-2d environment can cooperate with H-2k B cells.

H-2d spleen cells derived from either tetraparental or semiallogeneic radiation bone marrow chimeras can be primed to antigen within H-2d recipients to generate helper T cells capable of cooperating in a secondary response with equal efficiency with H-2d or H-2k B cells. Thus it would seem that the cooperative act between T and B cells does not require that the T cell interacts with its target B cells by either cell interaction genes or via an altered self mechanism involving both antigen and the target B-cell I-region products. This does not preclude a requirement for associative recognition or altered self in the interaction of helper T cells with accessory cells.

Antigen-specific T-cell factor in cell cooperation: physical properties and mapping in the left-hand (K) half of H-2.

Mouse thymus cells, educated to poly(tyrosyl,glutamyl)-polyDLalanyl--polylysyl [(T,G)-A--L], release an antigen-specific factor on brief culture in vitro. The factor cooperates with bone marrow cells in the antibody response to (T,G)-A--L in irradiated recipients. Its mol wt determined from Sephadex G100 chromatography is in the region of 50,000. The factor is removed by specific antigen-coated columns, but not by anti-immunoglobulin (anti-Fab, anti-micro, anti-Fv) adsorbents. The factor is removed by alloantisera directed against the H-2 haplotype of the strain in which it is produced. Moreover, only antisera with specificity for the K side of H-2 were successful in removing the factor activity.

Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers.

Further mapping of the mouse T-cell factor specific for poly(Try,Glu)-polyD-LAla--polyLys is reported. It is shown to be a product of the I-A subregion of the H-2 complex by the use of antisera either raised specifically against or made specific, by absorption, for different regions of the H-2 complex. The factor cooperates across allogeneic barriers, e.g., when factor produced by one strian is combined with bone marrow cells of other H-2 incompatible strains.

Improving paediatric antimicrobial stewardship in hospital-based settings: why, where and how?

BACKGROUND: Antimicrobial resistance (AMR) is being recognized as a priority by healthcare organizations across the world. However, many children are managed on IV antimicrobials in hospital with very little consideration of antimicrobial stewardship issues. OBJECTIVES: A nurse-led paediatric ambulatory outpatient parenteral antimicrobial therapy (OPAT) service, managing children with common infections being ambulated on short courses of IV antimicrobials, was introduced within Southampton Children's Hospital in January 2018. We evaluated the impact of this service in terms of the quality of antimicrobial prescribing and timing of ambulation in children presenting with common infections. METHODS: All cases managed within the service were reviewed in two separate 2 month time periods: prior to introduction of the service (September-October 2016) and then prospectively after its introduction (September-October 2018). RESULTS: A total of 96% of IV antibiotic management decisions at 48 h were deemed appropriate in 2018, compared with 75% in 2016. A total of 64% of patients were ambulated on IV antibiotics at some point during their treatment course in 2018, compared with 19% in 2016. However, a significant proportion of antimicrobial decisions made at the point of presentation to hospital remained suboptimal in 2018. CONCLUSIONS: Children are commonly managed with IV antibiotics in hospital. We demonstrate marked improvements in appropriate antimicrobial use through the introduction of a nurse-led ambulatory OPAT service. In addition, such a service can promote a greater proportion of children being ambulated from hospital, freeing up valuable inpatient beds and potentially delivering cost savings that can be used to fund such services.

Suspected malignant cord compression - improving time to diagnosis via a 'hotline': a prospective audit.

The aim of the study was to achieve earlier diagnosis of malignant cord compression (MCC) using urgent magnetic resonance imaging (MRI) for selected patients. A comparison was carried out of the current prospective audit of 100 patients referred by a general practitioner or a consultant over 32 months with both a previous national Clinical Research and Audit Group (CRAG) prospective audit (324 cases of MCC) and an earlier retrospective audit of 104 patients referred with suspected MCC. A telephone hotline rapid-referral process for patients with known malignancy and new symptoms (severe nerve root pain +/- severe back pain) was designed. Patients were considered for urgent MRI after discussion with a senior clinician responsible for the hotline. Appropriate referrals were discussed with radiology and oncology ensuring timely MRI reporting and intervention. The main outcome measures are as follows: time from referral to diagnosis; time from the onset of symptoms to diagnosis; and mobility at diagnosis. A total of 50 patients (52%) of those scanned had either MCC (44) or malignant nerve root compression (6) compared with the earlier rate of 23 out of 104 patients (22%). Ten out of 44 MCC patients (23%) were paralysed at diagnosis, compared with 149 out of 324 (46%) in the CRAG audit. Time from reporting pain to diagnosis was 32 days compared with 89 days in the CRAG audit. Median time from referral to diagnosis was 1 day, again considerably shorter than the CRAG audit time of 15 days (interquartile (IQ) range: 3-66). In patients at risk of MCC, fast-track referral with rapid access to MRI reduces time between symptom onset and diagnosis, improves mobility at diagnosis and reduces the number of negative MRI scans.

Transgenerational marking of freshwater fishes with enriched stable isotopes: a tool for fisheries management and research.

A promising new method of marking larval freshwater fishes with enriched stable isotopes by means of injecting the maternal parent with the marking agent was investigated. The (138)Ba:(137)Ba ratios in the otoliths of larval golden perch Macquaria ambigua were compared to determine the effect of injecting female broodstock with different dosages of enriched (137)Ba at various times before spawning. There was 100% mark success in the progeny of fish injected with 20 microg g(-1) of enriched (137)Ba 24 h before inducing spawning with hormones and 40 microg g(-1) administered at the same time as inducement of spawning. Injection of 40 microg g(-1) enriched (137)Ba 21 days before spawning resulted in only 81% mark success and suggests rapid elimination of barium in M. ambigua. Injection with enriched (137)Ba did not significantly affect the fertilization rate, number of fertilized eggs or hatching rate compared with long-term hatchery records. These results suggest that transgenerational marking is an effective and affordable means of mass-marking larval fishes. Thousands of larval fishes can be permanently marked with a unique artificial isotopic mark via a single injection into the maternal parent, thus avoiding the handling of individual fishes or having to deal with chemical baths. Because no single mark or tagging method is suitable for all situations, transgenerational marking with enriched stable isotopes provides another method for researchers and managers to discriminate both hatchery-reared and wild fishes.

Maternal respiratory distress and successful reversal with sugammadex during intrauterine transfusion with fetal paralysis.

A 70 kg, 34-year-old woman at 29 weeks-of-gestation required intrauterine transfusion for Rh (D) alloimmunization. In the ambulatory treatment clinic, 19 mg of rocuronium was administered intramuscularly in split doses into the fetal buttock. The fetus moved and inadvertent maternal neuromuscular blockade occurred, leading to respiratory distress. The patient was transferred to the operating room where she had poor muscle tone, dyspnea and dysphonia. Sugammadex 100 mg was administered intravenously and complete resolution of neuromuscular blockade was demonstrated using a Neuromuscular Transmission™ monitor. When neuromuscular blocking agents are administered in ambulatory settings, management protocols, reversal agents, and skilled assistance should be immediately available for managing potentially life-threatening complications.