Perioperative care of a patient with stroke.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Strokes and TIAs, with their high cumulative mortality and morbidity rates, are occurring with increasing frequency in western population 14. As such, it is vital for clinicians to provide optimal medical management in the perioperative period for those patients with this common neurological problem. This review aims to highlight the importance of the perioperative period and the stages of pre-optimization that can be taken by the multi-disciplinary team to aid this 171819. The evidence suggests that there are significant physiological advantages to early invasive monitoring and high dependency care in these complex patients. These cohort of patients are at increased risk of development of respiratory, gastrointestinal, nutritional and electrolyte disturbances so a constant vigil should be exercised in early recognition and treatment

Early career choices and successful career progression in surgery in the UK: prospective cohort studies

<p>Abstract</p> <p>Background</p> <p>Changes to the structure of medical training worldwide require doctors to decide on their career specialty at an increasingly early stage after graduation. We studied trends in career choices for surgery, and the eventual career destinations, of UK graduates who declared an early preference for surgery.</p> <p>Methods</p> <p>Postal questionnaires were sent, at regular time intervals after qualification, to all medical qualifiers from all UK medical schools in selected qualification years between 1974 and 2005. They were sent in the first year after qualification, at year three and five years after qualification, and at longer time intervals thereafter.</p> <p>Results</p> <p>Responses were received from 27 749 of 38 280 doctors (73%) at year one, 23 468 of 33151 (71%) at year three, and 17 689 of 24 870 (71%) at year five. Early career preferences showed that surgery has become more popular over the past two decades. Looking forward from early career choice, 60% of respondents (64% of men, 48% of women) with a first preference for a surgical specialty at year one eventually worked in surgery (p < 0.001 for the male-female comparison). Looking backward from eventual career destinations, 90% of responders working in surgery had originally specified a first choice for a surgical specialty at year one. 'Match' rates between eventual destinations and early choices were much higher for surgery than for other specialties. Considering factors that influenced early specialty choice 'a great deal', comparing aspiring surgeons and aspiring general practitioners (GPs), a significantly higher percentage who chose surgery than general practice specified enthusiasm for the specialty (73% vs. 53%), a particular teacher or department (34% vs. 12%), inclinations before medical school (20% vs. 11%), and future financial prospects (24% vs. 13%); and a lower percentage specified that hours and working conditions had influenced their choice (21% vs. 71%). Women choosing surgery were influenced less than men by their inclinations before medical school or by their future financial prospects.</p> <p>Conclusions</p> <p>Surgery is a popular specialty choice in the UK. The great majority of doctors who progressed in a surgical career made an early and definitive decision to do so.</p

Scientists and the 3Rs: attitudes to animal use in biomedical research and the effect of mandatory training in laboratory animal science

The 3Rs principle of replacement, reduction, and refinement has increasingly been endorsed by legislators and regulatory bodies as the best approach to tackle the ethical dilemma presented by animal experimentation in which the potential benefits for humans stand against the costs borne by the animals. Even when animal use is tightly regulated and supervised, the individual researcher’s responsibility is still decisive in the implementation of the 3Rs. Training in laboratory animal science (LAS) aims to raise researchers’ awareness and increase their knowledge, but its effect on scientists’ attitudes and practice has not so far been systematically assessed. Participants (n=206) in eight LAS courses (following the Federation of European Laboratory Animal Science Associations category C recommendations) in Portugal were surveyed in a self-administered questionnaire during the course. Questions were related mainly to the 3Rs and their application, attitudes to animal use and the ethical review of animal experiments. One year later, all the respondents were asked to answer a similar questionnaire (57% response rate) with added self-evaluation questions on the impact of training. Our results suggest that the course is effective in promoting awareness and increasing knowledge of the 3Rs, particularly with regard to refinement. However, participation in the course did not change perceptions on the current and future needs for animal use in research

Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial): a mixed methods study

OBJECTIVE: To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. DESIGN: Mixed methods study with data collected at three time points: (1) before, (2) during and (3) after a pilot trial. SETTING: English, Paediatric Intensive Care Units (PICUs). PARTICIPANTS: (1) Pre-pilot trial focus groups with pilot site staff (n=56) and interviews with parents (n=25) whose child had been admitted to PICU in the last 3 years with a fever and suspected infection, (2) Questionnaires with parents of randomised children following pilot trial recruitment (n=48 from 47 families) and (3) post-pilot trial interviews with parents (n=19), focus groups (n=50) and a survey (n=48) with site staff. Analysis drew on Sekhon et al's theoretical framework of acceptability. RESULTS: There was initial support for the trial, yet some held concerns regarding the proposed temperature thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed protocol changes and training, which influenced views on trial acceptability. Staff trained by the FEVER team found the trial more acceptable than those trained by colleagues. Parents and staff found the trial acceptable. Some concerns about pain or discomfort during weaning from ventilation remained. CONCLUSIONS: Pre-trial findings and pilot trial experience influenced acceptability, providing insight into how challenges may be overcome. We present an adapted theoretical framework of acceptability to inform future trial feasibility studies. TRIAL REGISTRATION NUMBERS: ISRCTN16022198 and NCT03028818

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Targeting glutamatergic and cellular prion protein mechanisms of amyloid β-mediated persistent synaptic plasticity disruption: longitudinal studies

Alzheimer's disease amyloid-β (Aβ) oligomers are synaptotoxic, inappropriately increasing extracellular glutamate concentration and glutamate receptor activation to thereby rapidly disrupt synaptic plasticity. Thus, acutely promoting brain glutamate homeostasis with a blood-based scavenging system, glutamate-oxaloacetate transaminase (GOT), and blocking metabotropic glutamate 5 (mGlu5) receptor or its co-receptor cellular prion protein (PrP), prevent the acute inhibition of long-term potentiation (LTP) by exogenous Aβ. Here, we evaluated the time course of the effects of such interventions in the persistent disruptive effects of Aβ oligomers, either exogenously injected in wild type rats or endogenously generated in transgenic rats that model Alzheimer's disease amyloidosis. We report that repeated, but not acute, systemic administration of recombinant GOT type 1, with or without the glutamate co-substrate oxaloacetate, reversed the persistent deleterious effect of exogenous Aβ on synaptic plasticity. Moreover, similar repetitive treatment reversibly abrogated the inhibition of LTP monitored longitudinally in freely behaving transgenic rats. Remarkably, brief repeated treatment with an mGlu5 receptor antagonist, basimglurant, or an antibody that prevents Aβ oligomer binding to PrP, ICSM35, also had similar reversible ameliorative effects in the transgenic rat model. Overall, the present findings support the ongoing development of therapeutics for early Alzheimer's disease based on these complementary approaches

Popliteal block with transfibular approach in ankle arthrodesis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Ankle arthrodesis is primarily undertaken to control severe pain in the ankle joint. Immediate postoperative pain is usually treated using oral analgesics, intravenous opiates and regional anaesthesia. The outcomes of ankle fusion, including patient satisfaction studies, are well documented in the literature. However, the advantage of popliteal block in the management of early postoperative pain after ankle fusion for osteoarthritis has not been widely reported. This study aims to determine the role of popliteal block using ankle fusion in the management of ankle osteoarthritis.</p> <p>Case presentation</p> <p>Ankle arthrodeses were performed in 27 patients over a five-year period. Eighteen patients were males (one had bilateral arthrodesis) and eight were females. Their mean age was 56 years and they were all Caucasians. The notes and radiographs of the patients were reviewed in retrospect for the duration of their hospital admission, time to union and complications.</p> <p>Conclusion</p> <p>Popliteal block is a safe and effective technique for postoperative analgesia in ankle arthrodesis. By using this technique, we achieved a significant reduction in the duration of hospital stay for our patients after ankle arthrodesis. The resultant cost saving was GBP717 for each patient.</p

Cancer mortality in 13 to 29-year-olds in England and Wales, 1981–2005

We examined cancer mortality at ages 13–29 years in England and Wales between 1981 and 2005, a total of 20 026 deaths over approximately 303 million person-years (mpy) at risk by sex, age group and time period. Overall, the mortality rate was 65.6 per mpy. Malignant neoplasms of the central nervous system showed the highest rate (8.5), followed by myeloid and monocytic leukaemia (6.6), lymphoid leukaemia (6.4), malignant bone tumours (5.4) and non-Hodgkin's lymphoma (5.2). These groups together accounted for almost 50% of all cancer deaths. The mortality rate for males (72.4) was 23% higher than for females (58.6) (P-value <0.0001). Males showed significantly higher mortality rates than females in almost all diagnostic groups, in general, mortality increasing with age (P-value <0.0001). There were significant decreases in mortality over time, the annual percentage change between 1981 and 2005 being minus 1.86 (95% confidence interval −2.09 to −1.62). Cancer groups with the highest mortality differed from those with the highest incidence

Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial

BACKGROUND: Oxygen saturation monitoring for children receiving respiratory support is standard worldwide. No randomised clinical trials have compared peripheral oxygen saturation (SpO_{2}) targets for critically ill children. The harm of interventions to raise SpO_{2} to > 94% may exceed their benefits. METHODS: We undertook an open, parallel-group randomised trial of children > 38 weeks completed gestation and  94%) or a conservative oxygenation group (SpO_{2} = 88–92% inclusive). Outcomes were measures of feasibility: recruitment rate, protocol adherence and acceptability, between-group separation of SpO_{2} and safety. The Oxy-PICU trial was registered before recruitment: ClinicalTrials.gov identifier NCT03040570. RESULTS: A total of 159 children met the inclusion criteria, of whom 119 (75%) were randomised between April and July 2017, representing a rate of 10 patients per month per site. The mean time to randomisation from first contact with an intensive care team was 1.9 (SD 2.2) h. Consent to continue in the study was obtained in 107 cases (90%); the children’s parents/legal representatives were supportive of the consent process. The median (interquartile range, IQR) of time-weighted individual mean SpO_{2} was 94.9% (92.6–97.1) in the conservative oxygenation group and 97.5% (96.2–98.4) in the liberal group [difference 2.7%, 95% confidence interval (95% CI) 1.3–4.0%, p < 0.001]. Median (IQR) time-weighted individual mean FiO_{2} was 0.28 (0.24–0.37) in the conservative group and 0.37 (0.30–0.42) in the liberal group (difference 0.08, 95% CI 0.03–0.13, p < 0.001). There were no significant between-group differences in length of stay, duration of organ support or mortality. Two prespecified serious adverse events (cardiac arrests) occurred, both in the liberal oxygenation group. CONCLUSION: A definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children