Showing papers by "Leicester Royal Infirmary published in 2014"

Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: meta-analysis

Abstract: Objective: To investigate whether people with subjective memory complaints (SMC) but no objective deficits are at increased risk of developing mild cognitive impairment (MCI) and dementia. Method: Major electronic databases were searched till 03/2014, and a meta-analysis was conducted using inception cohort studies. Results: Across 28 studies, there were 29 723 unique individuals (14 714 with SMC and 15 009 without SMC) (mean 71.6 years) followed on average for 4.8 years through to dementia. The annual conversion rate (ACR) of SMC to dementia was 2.33% (95% CI = 1.93%–2.78%) a relative risk (RR) of 2.07 (95% CI = 1.76–2.44) compared with those without SMC (n = 15 009). From 11 studies the ACR of developing MCI was 6.67% (95% CI = 4.70–8.95%). In long-term studies over 4 years, 14.1% (9.67–19.1%) of people with SMC developed dementia and 26.6% (95% CI = 5.3–39.7) went on to develop MCI. The ACR from SMC to dementia and MCI were comparable in community and non-community settings. Conclusion: Older people with SMC but no objective complaints are twice as likely to develop dementia as individuals without SMC. Approximately 2.3% and 6.6% of older people with SMC will progress to dementia and MCI per year.

Treatment for Primary Postpartum Haemorrhage

Abstract: Background Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries. Objectives To assess the effectiveness and safety of any intervention used for the treatment of primary PPH. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013). Selection criteria Randomised controlled trials comparing any interventions for the treatment of primary PPH. Data collection and analysis We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information. Main results Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review. Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering. Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes. One study compared lower segment compression but was too small to assess impact on primary outcomes. We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics. Authors' conclusions Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit. The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.

Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.

Abstract: Summary Background The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. Methods For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m 2 ; 250 mg/m 2 once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0·55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. The trial is registered with ClinicalTrials.gov, number NCT01001377. Findings Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab ( Z score −3·19; p=0·0007). Median overall survival was 10·4 months (95% CI 9·4–11·6) with panitumumab and 10·0 months (9·3–11·0) with cetuximab (HR 0·97; 95% CI 0·84–1·11). Panitumumab retained 105·7% (81·9–129·5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3–4 was similar across treatment groups. Grade 3–4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3–4 infusion reactions was lower with panitumumab than with cetuximab (one [ vs nine [2%] patients), and the occurrence of grade 3–4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab. Interpretation Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3–4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. Funding Amgen Inc.

Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial

Abstract: Summary Background Patients with advanced-stage, low-tumour-burden follicular lymphoma have conventionally undergone watchful waiting until disease progression. We assessed whether rituximab use could delay the need for chemotherapy or radiotherapy compared with watchful waiting and the effect of this strategy on quality of life (QoL). Methods Asymptomatic patients (aged ≥18 years) with low-tumour-burden follicular lymphoma (grades 1, 2, and 3a) were randomly assigned centrally (1:1:1), by the minimisation approach stratified by institution, grade, stage, and age, to watchful waiting, rituximab 375 mg/m 2 weekly for 4 weeks (rituximab induction), or rituximab induction followed by a maintenance schedule of 12 further infusions given at 2-monthly intervals for 2 years (maintenance rituximab). On Sept 30, 2007, recruitment into the rituximab induction group was closed and the study was amended to a two-arm study. The primary endpoints were time to start of new treatment and QoL at month 7 (ie, 6 months after completion of rituximab induction). All randomly assigned patients were included in the analysis of time to start of new treatment on an intention-to-treat basis. The main study is now completed and is in long-term follow-up. The study is registered with ClinicalTrials.gov, NCT00112931. Findings Between Oct 15, 2004, and March 25, 2009, 379 patients from 118 centres in the UK, Australia, New Zealand, Turkey, and Poland were randomly assigned to watchful waiting or maintenance rituximab. 84 patients were recruited to the rituximab induction group before it was closed early. There was a significant difference in the time to start of new treatment, with 46% (95% CI 39–53) of patients in the watchful waiting group not needing treatment at 3 years compared with 88% (83–92) in the maintenance rituximab group (hazard ratio [HR] 0·21, 95% CI 0·14–0·31; p Interpretation Rituximab monotherapy should be considered as a treatment option for patients with asymptomatic, advanced-stage, low-tumour-burden follicular lymphoma. Funding Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.

Diagnosis and management of primary ciliary dyskinesia

Abstract: Primary ciliary dyskinesia (PCD) is an inherited autosomal-recessive disorder of motile cilia characterised by chronic lung disease, rhinosinusitis, hearing impairment and subfertility. Nasal symptoms and respiratory distress usually start soon after birth, and by adulthood bronchiectasis is invariable. Organ laterality defects, usually situs inversus, occur in ∼50% of cases. The estimated prevalence of PCD is up to ∼1 per 10,000 births, but it is more common in populations where consanguinity is common. This review examines who to refer for diagnostic testing. It describes the limitations surrounding diagnosis using currently available techniques and considers whether recent advances to genotype patients with PCD will lead to genetic testing and screening to aid diagnosis in the near future. It discusses the challenges of monitoring and treating respiratory and ENT disease in children with PCD.

Screening for poststroke major depression: a meta-analysis of diagnostic validity studies

Abstract: Background Major depression is common in stroke patients and associated with increased rates of disability and mortality. Identifying depression may improve mental and physical health. The aim of this review was to determine the most accurate tool for detecting poststroke depression. Methods Seven databases were searched up to November 2012. Two authors selected studies using International Classification of Disease or Diagnostic and Statistical Manual diagnosis of depression as the reference standard. Two authors extracted data and assessed methodological quality. Included studies were synthesised using meta-analyses. Results A total of 24 included studies provided data on 2907 participants. The Center of Epidemiological Studies-Depression Scale (CESD) (sensitivity: 0.75; 95% CI 0.60 to 0.85; specificity: 0.88; 95% CI 0.71 to 0.95), the Hamilton Depression Rating Scale (HDRS) (sensitivity: 0.84; 95% CI 0.75 to 0.90; specificity:0.83; 95% CI 0.72 to 0.90) and the Patient Health Questionnaire (PHQ)-9 (sensitivity: 0.86; 95% CI 0.70 to 0.94; specificity: 0.79; 95% CI 0.60 to 0.90) appeared to be the optimal measures for screening measures. However, the clinical utility of all tools was modest for case-finding. Interpretation There are a number of possible instruments that may help in screening for poststroke depression but none are satisfactory for case-finding. Preliminary data suggests the CESD, HDRS or the PHQ-9 as the most promising options. Although it should be noted such scales should not be used in isolation but followed up with a more detailed clinical assessment. While there is promising data for the PHQ-2 in other populations, it performed less well than other measures.

A controlled evaluation of comprehensive geriatric assessment in the emergency department: the ‘Emergency Frailty Unit’

Abstract: Background: the ageing demographic means that increasing numbers of older people will be attending emergency departments (EDs). Little previous research has focused on the needs of older people in ED and there have been no evaluations of comprehensive geriatric assessment (CGA) embedded within the ED setting. Methods: a pre-post cohort study of the impact of embedding CGA within a large ED in the East Midlands, UK. The primary outcome was admission avoidance from the ED, with readmissions, length of stay and bed-day use as secondary outcomes. Results: attendances to ED increased in older people over the study period, whereas the ED conversion rate fell from 69.6 to 61.2% in people aged 85+, and readmission rates in this group fell from 26.0% at 90 days to 19.9%. In-patient bed-day use increased slightly, as did the mean length of stay. Discussion: it is possible to embed CGA within EDs, which is associated with improvements in operational outcomes.

Driving with binocular visual field loss? A study on a supervised on-road parcours with simultaneous eye and head tracking

Abstract: Post-chiasmal visual pathway lesions and glaucomatous optic neuropathy cause binocular visual field defects (VFDs) that may critically interfere with quality of life and driving licensure. The aims of this study were (i) to assess the on-road driving performance of patients suffering from binocular visual field loss using a dual-brake vehicle, and (ii) to investigate the related compensatory mechanisms. A driving instructor, blinded to the participants' diagnosis, rated the driving performance (passed/failed) of ten patients with homonymous visual field defects (HP), including four patients with right (HR) and six patients with left homonymous visual field defects (HL), ten glaucoma patients (GP), and twenty age and gender-related ophthalmologically healthy control subjects (C) during a 40-minute driving task on a pre-specified public on-road parcours. In order to investigate the subjects' visual exploration ability, eye movements were recorded by means of a mobile eye tracker. Two additional cameras were used to monitor the driving scene and record head and shoulder movements. Thus this study is novel as a quantitative assessment of eye movements and an additional evaluation of head and shoulder was performed. Six out of ten HP and four out of ten GP were rated as fit to drive by the driving instructor, despite their binocular visual field loss. Three out of 20 control subjects failed the on-road assessment. The extent of the visual field defect was of minor importance with regard to the driving performance. The site of the homonymous visual field defect (HVFD) critically interfered with the driving ability: all failed HP subjects suffered from left homonymous visual field loss (HL) due to right hemispheric lesions. Patients who failed the driving assessment had mainly difficulties with lane keeping and gap judgment ability. Patients who passed the test displayed different exploration patterns than those who failed. Patients who passed focused longer on the central area of the visual field than patients who failed the test. In addition, patients who passed the test performed more glances towards the area of their visual field defect. In conclusion, our findings support the hypothesis that the extent of visual field per se cannot predict driving fitness, because some patients with HVFDs and advanced glaucoma can compensate for their deficit by effective visual scanning. Head movements appeared to be superior to eye and shoulder movements in predicting the outcome of the driving test under the present study scenario.

Functional plasticity of the N/OFQ‐NOP receptor system determines analgesic properties of NOP receptor agonists

Abstract: Despite high sequence similarity between NOP (nociceptin/orphanin FQ opioid peptide) and opioid receptors, marked differences in endogenous ligand selectivity, signal transduction, phosphorylation, desensitization, internalization and trafficking have been identified; underscoring the evolutionary difference between NOP and opioid receptors. Activation of NOP receptors affects nociceptive transmission in a site-specific manner, with antinociceptive effects prevailing after peripheral and spinal activation, and pronociceptive effects after supraspinal activation in rodents. The net effect of systemically administered NOP receptor agonists on nociception is proposed to depend on the relative contribution of peripheral, spinal and supraspinal activation, and this may depend on experimental conditions. Functional expression and regulation of NOP receptors at peripheral and central sites of the nociceptive pathway exhibits a high degree of plasticity under conditions of neuropathic and inflammatory pain. In rodents, systemically administered NOP receptor agonists exerted antihypersensitive effects in models of neuropathic and inflammatory pain. However, they were largely ineffective in acute pain while concomitantly evoking severe motor side effects. In contrast, systemic administration of NOP receptor agonists to non-human primates (NHPs) exerted potent and efficacious antinociception in the absence of motor and sedative side effects. The reason for this species difference with respect to antinociceptive efficacy and tolerability is not clear. Moreover, co-activation of NOP and μ-opioid peptide (MOP) receptors synergistically produced antinociception in NHPs. Hence, both selective NOP receptor as well as NOP/MOP receptor agonists may hold potential for clinical use as analgesics effective in conditions of acute and chronic pain.

Rituximab Plus Chlorambucil As First-Line Treatment for Chronic Lymphocytic Leukemia: Final Analysis of an Open-Label Phase II Study

Abstract: Purpose Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL. Patients and Methods Patients with first-line CLL were treated with rituximab (375 mg/m2 on day 1, cycle one, and 500 mg/m2 thereafter) plus chlorambucil (10 mg/m2/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety. Results A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (rang...

Prevalence of Eating Disorders amongst Dancers: A Systemic Review and Meta-Analysis

Abstract: Eating disorders in dancers are thought to be common, but the exact rates remain to be clarified. The aim of this study is to systematically compile and analyse the rates of eating disorde rs in dancers. A literature search, appraisal and meta-analysis were conducted. Thi rty-three relevant studies were published between 1966 and 2013 with sufficient data for extraction. Primary data were extracted as raw numbers or confidence intervals. Risk ratios and 95% confidence intervals were calculated for controlled studies. The overall prevalence of eating disorders was 12.0% (16.4% for ballet dancers), 2.0% (4% for bal let dancers) for anorexia, 4.4% (2% for ballet dancers) for bulimia and 9.5% (14.9% for ballet dancers) for eating disorders not otherwise specified (EDNOS). The dancer group had higher mean scores on the EAT-26 and the Eating Disorder Inventory subscales. Dancers, in general, had a higher risk of suffering from eating disorders in general, anorexia nervosa and EDNOS, but no higher risk of suffering from bulimia nervosa. The study concluded that as dancers had a three times higher risk of suffering from eating disorders, particularly anorexia nervosa and EDNOS, specifically designed services for this population should be considered

Nystagmus in Childhood

Abstract: Nystagmus is an involuntary rhythmic oscillation of the eyes, which leads to reduced visual acuity due to the excessive motion of images on the retina Nystagmus can be grouped into infantile nystagmus (IN), which usually appears in the first 3-6 months of life, and acquired nystagmus (AN), which appears later IN can be idiopathic or associated to albinism, retinal disease, low vision, or visual deprivation in early life, for example due to congenital cataracts, optic nerve hypoplasia, and retinal dystrophies, or it can be part of neurological syndromes and neurologic diseases It is important to differentiate between infantile and acquired nystagmus This can be achieved by considering not only the time of onset of the nystagmus, but also the waveform characteristics of the nystagmus Neurological disease should be suspected when the nystagmus is asymmetrical or unilateral Electrophysiology, laboratory tests, neurological, and imaging work-up may be necessary, in order to exclude any underlying ocular or systemic pathology in a child with nystagmus Furthermore, the recent introduction of hand-held spectral domain optical coherence tomography (HH SD-OCT) provides detailed assessment of foveal structure in several pediatric eye conditions associated with nystagmus and it can been used to determine the underlying cause of infantile nystagmus Additionally, the development of novel methods to record eye movements can help to obtain more detailed information and assist the diagnosis Recent advances in the field of genetics have identified the FRMD7 gene as the major cause of hereditary X-linked nystagmus, which will possibly guide research towards gene therapy in the future Treatment options for nystagmus involve pharmacological and surgical interventions Clinically proven pharmacological treatments for nystagmus, such as gabapentin and memantine, are now beginning to emerge In cases of obvious head posture, eye muscle surgery can be performed to shift the null zone of the nystagmus into the primary position, and also to alleviate neck problems that can arise due to an abnormal head posture

ISPAD Clinical Practice Consensus Guidelines 2014. Diabetes education in children and adolescents.

Abstract: Karin Langea, Peter Swiftb, Ewa Pańkowskac and Thomas Danned aDepartment of Medical Psychology, Hannover Medical School, OE 5430, 30625, Hannover, Germany; bChildrens Hospital, Leicester Royal Infirmary, Leicester, LE1 5WW, UK; cThe Institute of Diabetology, ul. Żegańska 46a, 04-736, Warszawa, Poland; and dDiabetes Centre for Children and Adolescents at the Kinderund Jugendkrankenhaus, Auf der Bult, Janusz-Korczak-Allee 12, 30173, Hannover, Germany

Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study

Abstract: Summary Background Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected melanoma at high risk of recurrence. We report results from the preplanned interim analysis. Methods We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage (AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based minimisation procedure, to receive intravenous bevacizumab 7·5 mg/kg, every 3 weeks for 1 year, or to observation. Randomisation was stratified by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria, ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306. Findings 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672). Median follow-up was 25 months (IQR 16–37) in the bevacizumab group and 25 months (17–37) in the observation group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab group died because of melanoma versus 139 (95%) in the observation group. We noted no significant difference in overall survival between treatment groups (hazard ratio [HR] 0·97, 95% CI 0·78–1·22; p=0·76); this finding persisted after adjustment for stratification variables (HR 1·03; 95% CI 0·81–1·29; p=0·83). Median duration of treatment with bevacizumab was 51 weeks (IQR 21–52) and dose intensity was 86% (41–96), showing good tolerability. 180 grade 3 or 4 adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation (41 [6%] vs one [ Interpretation Bevacizumab has promising tolerability. Longer follow-up is needed to identify an effect on the primary endpoint of overall survival at 5 years. Funding Cancer Research UK.

Radioimmunoassay, enzyme and non-enzyme-based immunoassays

Abstract: The ability to quantify the amount of a specific protein in a complex sample has been a valuable addition to laboratory science, allowing the development of diagnostic tests, allergen detection in the food industry,and screening for immunity. This is particularly important in anaesthesia, intensive care, and pain research for the quantification of mediators (cytokines, peptides, and analytes) involved in inflammation, pain, and other pathways. Immunoassays use the high specificity of antibodies, along with their enormous diversity, to target specific molecules of interest and analyse their concentration in a sample. The first immunoassay developed was described by Yalow and Berson in 1959. They used radiolabelled insulin to assess the concentration of insulin in human plasma, and thus developed the first radioimmunoassay (RIA). In 1971, Engvail and Perlman described a technique whereby antigens were immobilized on a microplate well, incubated with antiserum, and then the concentration of antibody in the antiserum was quantified using an enzyme-linked anti-immunoglobulin antibody. This method is the enzyme-linked immunosorbent assay (ELISA). Enzyme immunoassays (EIAs) are very similar to ELISAs, and as such, the terms are often used interchangeably. The EIA was developed by Van Weemen and Schuurs (independently of Engvail and Perlman) for the quantification of antigen rather than antibody. For the purpose of this article, EIA and ELISA should be considered interchangeable. The majority of RIA assay formats recommend sample cleaning and concentration (particularly when analyte concentration and assay sensitivity is low), although a large number of ELISA assays can cope with direct use of unprocessed plasma. The cleaning and concentration process usually involves ion exchange chromatography followed by some form of freeze drying/lyophilization. We would recommend users to determine if sample cleaning is required for their analyte. Often, there are differences in measured analyte concentration when comparing RIA and ELISA. This can result from specificity of the antibody (e.g. the cardiovascular peptide urotensin II) 6 or the fluid in which the analyte is suspended interfering with only one type of assay (e.g. the opioid-related peptide Nociceptin/Orphanin FQ). – 11 Discordance has also been demonstrated between RIAs and EIAs measuring cortisol and carcinoembryonic antigen. 13 The selection of assay format is therefore critical and the remainder of this article covers the main formats currently available.

The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran

Abstract: Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not ‘routine’. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s).

Complications after volar locking plate fixation of distal radius fractures

Abstract: Volar locking plates are an increasingly popular treatment for distal radius fractures. We reviewed complications observed after volar locking plate fixation in a busy teaching hospital. The purpose of the study was to assess whether complication rates after volar locking plate use in general, routine trauma practice were higher than published literature from expert users. A retrospective review was carried out of patients treated with a volar locking plate between January 2009 and December 2010. The series included 206 procedures in 204 patients (77 males and 127 females) with mean age of 55 years (range 16-94). Surgery was performed by 18 different consultant surgeons and 11 registrars. A total of 22 complications were observed in 20 patients with an overall complication rate of 9.7%. Seven (3.4%) patients developed tendon problems including four (1.9%) tendon ruptures. Four (1.9%) patients required re-operation for metalwork problems; four patients developed complex regional pain syndrome (CRPS). Three fracture reduction problems were noted. A total of 16 further operations were carried out for complications. The overall complication rate was low even when surgery was done by many surgeons, suggesting that this is a safe and reproducible technique. This study provides information which can be used to counsel patients about risks, including those of tendon and metalwork problems. This allows patients to make an informed decision. Surgeons must have specific strategies to avoid these complications and remain vigilant so that these can be identified and managed early.

Allergy to oxidized limonene and linalool is frequent in the U.K.

Abstract: SummaryBackground The oxidized forms of the fragrance terpenes limonene and linalool are known to cause allergic contact dermatitis. Significant rates of contact allergy to these fragrances have been reported in European studies and in a recent worldwide study. Patch testing to oxidized terpenes is not routinely carried out either in the U.K. or in other centres internationally. Objectives To investigate the prevalence of contact allergy to oxidized limonene and linalool in the U.K. Methods Between 1 August 2011 and 31 December 2012, 4731 consecutive patients in 13 U.K. dermatology departments were tested for hydroperoxides of limonene 0·3% pet., hydroperoxides of linalool 1·0% pet., stabilized limonene 10·0% pet. and stabilized linalool 10·0% pet. Doubtful (?+) and equivocal (±) reactions were grouped together as irritant reactions. Results Two hundred and thirty-seven patients (5·0%) had a positive patch test reaction to hydroperoxides of limonene 0·3% pet. and 281 (5·9%) to hydroperoxides of linalool 1·0% pet. Irritant reactions to one or both oxidized terpenes were found in 242 patients (7·3%). Eleven patients (0·2%) had a positive patch test reaction to the stabilized terpenes alone. Conclusions This large, multicentre U.K. audit shows a significant rate of allergy to the hydroperoxides of limonene and linalool plus a high rate of irritant reactions. Testing to the oxidized forms alone captures the majority (97·0%; 411 of 422) of positive reactions; testing to nonoxidized terpenes appears to be less useful. We recommend that the hydroperoxides of limonene and linalool be added to an extended baseline patch test series.

Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects

Abstract: Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant [“artificial scotoma” (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.

Taste, Smell and Appetite Change After Roux-en-Y Gastric Bypass Surgery

Abstract: It is apparent from day-to-day practice that patients frequently report changes to their appetite, taste and smell after weight loss surgery. There has been surprisingly little written in the literature on this. The aim of the current study was to assess these parameters in a cohort of patients undergoing Roux-en-Y gastric bypass surgery. Questionnaires relating to appetite, taste and smell were administered to 188 patients who had undergone Roux-en-Y gastric bypass surgery at our institution during the years 2000–2011. Responses were received from 103 patients (55 %). Sensory changes in appetite, taste and smell were noted by 97, 73 and 42 % of patients, respectively. Seventy-three percent of patients reported aversion to specific foods after surgery, with meat products the most commonly cited (33 %). Patients who experienced food aversions experienced more postoperative weight loss and reduction in BMI, compared to their counterparts without these features. This study indicates that subjective changes in appetite, taste and smell are very common after Roux-en-Y gastric bypass. Patients are now routinely counselled about these changes as part of the informed consent process for surgery.

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within a general practice (primary care) setting

Abstract: Background The IQCODE (Informant Questionnaire for Cognitive Decline in the Elderly) is a commonly used questionnaire based tool that uses collateral information to assess for cognitive decline and dementia. Brief tools that can be used for dementia "screening" or "triage" may have particular utility in primary care / general practice healthcare settings but only if they have suitable test accuracy. A synthesis of the available data regarding IQCODE accuracy in a primary care setting should help inform cognitive assessment strategies for clinical practice; research and policy. Objectives We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard). In this review we focus on those studies conducted in a primary care (general practice) setting. Search methods A search was performed in the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS (Ovid SP), ISI Web of Science and Conference Proceedings (ISI Web of Knowledge), CINHAL (EBSCOhost) and LILACs (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (York University); HTA Database (Health Technology Assessments Database via The Cochrane Library) and ARIF (Birmingham University). We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel and included terms relating to cognitive tests, cognitive screening and dementia. We used standardized database subject headings such as MeSH terms (in MEDLINE) and other standardized headings (controlled vocabulary) in other databases, as appropriate. Selection criteria We selected those studies performed in primary care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the "primary care" setting, we included those healthcare settings where unselected patients, present for initial, non-specialist assessment of memory or non-memory related symptoms; often with a view to onward referral for more definitive assessment. Data collection and analysis We screened all titles generated by electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. Quality assessment (risk of bias and applicability) was determined using the QUADAS-2 tool. Reporting quality was determined using the STARDdem extension to the STARD tool. Main results From 71 papers describing IQCODE test accuracy, we included 1 paper, representing data from 230 individuals (n=16 [7%] with dementia). The paper described those patients consulting a primary care service who self-identified as Japanese-American. Dementia diagnosis was made using Benson & Cummings criteria and the IQCODE was recorded as part of a longer interview with the informant. IQCODE accuracy was assessed at various test thresholds, with a "trade-off" between sensitivity and specificity across these cutpoints. At an IQCODE threshold of 3.2 sensitivity: 100%, specificity: 76%; for IQCODE 3.7 sensitivity: 75%, specificity: 98%. Applying the QUADAS-2 assessments, the study was at high risk of bias in all categories. In particular degree of blinding was unclear and not all participants were included in the final analysis. Authors' conclusions It is not possible to give definitive guidance on the test accuracy of IQCODE for the diagnosis of dementia in a primary care setting based on the single study identified. We are surprised by the lack of research using the IQCODE in primary care as this is, arguably, the most appropriate setting for targeted case finding of those with undiagnosed dementia in order to maximise opportunities to intervene and provide support for the individual and their carers.

Expression of PD-1 (CD279) and FoxP3 in diffuse large B-cell lymphoma

Abstract: The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4(+) T-cells ( 50 % of all lymph node cells) and PD-1(hi) cells (0.1 to 1.5 % of all cells). CD4(+) T-cells can be distributed in clusters or more diffusely and PD-1(hi) cells, but not FoxP3(+) cells, are found in rosettes around lymphoma cells. Cases with high CD4(+) T-cell numbers tended to have higher numbers of both PD-1(hi) and FoxP3(+) cells. Cases with total CD4(+) T-cell, PD-1(hi) and FoxP3(+) numbers above the median associate with better clinical outcome. Overall, we demonstrate that infiltration by CD4(+) T-cells, including both FoxP3(+) and PD-1(hi) subsets, correlates with prognosis in DLBCL. In distinction to previous reported series, patients (91 %) were treated with rituximab-containing regimens, suggesting that the effects of CD4+ T-cell infiltration are maintained in the rituximab era. This work suggests that determinants of total CD4(+) T-cell infiltration, either molecular characteristics of the lymphoma or the patients' immune system, and not individual T-cell subsets, correlate with clinical outcome.

Overexpression of the Nek2 Kinase in Colorectal Cancer Correlates With Beta-Catenin Relocalization and Shortened Cancer-Specific Survival

Abstract: The serine/threonine kinase Nek2 (NIMA‐related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing inductionofaneuploidyinvitro.Overexpression mayalsoenabletumourprogressionthrougheffects uponAktsignalling, celladhesionmarkersand the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC). Nek2 protein expression was examined in a panel of CRC cell lines using Western blotting and immunofluorescence microscopy. Nek2 and beta‐catenin expression were examined by immunohistochemistry in a series of resected CRC, as well as their matched lymph node and liver metastases, and correlated with clinicopathological characteristics. Nek2 protein expression in all CRC lines examined was higher than in the immortalised colonocyte line HCEC. Nek2 overexpression was present in 86.4% of resected CRC and was significantly associated with advancing AJCC tumour stage and shortened cancer‐specific survival. Elevated Nek2 expression was maintained within all matched metastases from overexpressing primary tumours. Nek2 overexpression was significantly associated with lower tumour membranous beta‐catenin expression and higher cytoplasmic and nuclear beta‐ catenin accumulation. These data support a role for Nek2 in CRC progression and confirm potential for Nek2 inhibition as a therapeutic avenue in CRC. J. Surg. Oncol. . 2014 Wiley Periodicals, Inc.

Binocular Glaucomatous Visual Field Loss and Its Impact on Visual Exploration - A Supermarket Study

Abstract: Advanced glaucomatous visual field loss may critically interfere with quality of life. The purpose of this study was to (i) assess the impact of binocular glaucomatous visual field loss on a supermarket search task as an example of everyday living activities, (ii) to identify factors influencing the performance, and (iii) to investigate the related compensatory mechanisms. Ten patients with binocular glaucoma (GP), and ten healthy-sighted control subjects (GC) were asked to collect twenty different products chosen randomly in two supermarket racks as quickly as possible. The task performance was rated as “passed” or “failed” with regard to the time per correctly collected item. Based on the performance of control subjects, the threshold value for failing the task was defined as μ+3σ (in seconds per correctly collected item). Eye movements were recorded by means of a mobile eye tracker. Eight out of ten patients with glaucoma and all control subjects passed the task. Patients who failed the task needed significantly longer time (111.47 s ±12.12 s) to complete the task than patients who passed (64.45 s ±13.36 s, t-test, p<0.001). Furthermore, patients who passed the task showed a significantly higher number of glances towards the visual field defect (VFD) area than patients who failed (t-test, p<0.05). According to these results, glaucoma patients with defects in the binocular visual field display on average longer search times in a naturalistic supermarket task. However, a considerable number of patients, who compensate by frequent glancing towards the VFD, showed successful task performance. Therefore, systematic exploration of the VFD area seems to be a “time-effective” compensatory mechanism during the present supermarket task.