The SOAR stroke score predicts hospital length of stay in acute stroke: an external validation study.

AIMS: The objective of this study is to externally validate the SOAR stroke score (Stroke subtype, Oxfordshire Community Stroke Project Classification, Age and prestroke modified Rankin score) in predicting hospital length of stay (LOS) following an admission for acute stroke. METHODS: We conducted a multi-centre observational study in eight National Health Service hospital trusts in the Anglia Stroke & Heart Clinical Network between September 2008 and April 2011. The usefulness of the SOAR stroke score in predicting hospital LOS in the acute settings was examined for all stroke and then stratified by discharge status (discharged alive or died during the admission). RESULTS: A total of 3596 patients (mean age 77 years) with first-ever or recurrent stroke (92% ischaemic) were included. Increasing LOS was observed with increasing SOAR stroke score (p < 0.001 for both mean and median) and the SOAR stroke score of 0 had the shortest mean LOS (12 ± 20 days) while the SOAR stroke score of 6 had the longest mean LOS (26 ± 28 days). Among patients who were discharged alive, increasing SOAR stroke score had a significantly higher mean and median LOS (p < 0.001 for both mean and median) and the LOS peaked among patients with score value of 6 [mean (SD) 35 ± 31 days, median (IQR) 23 (14-48) days]. For patients who died as in-patient, there was no significant difference in mean or median LOS with increasing SOAR stroke score (p = 0.68 and p = 0.79, respectively). CONCLUSION: This external validation study confirms the usefulness of the SOAR stroke score in predicting LOS in patients with acute stroke especially in those who are likely to survive to discharge. This provides a simple prognostic score useful for clinicians, patients and service providers.

MRSA screening in the vascular day-case population.

INTRODUCTION: The UK Government has prioritised methicillin-resistant Staphylococcus aureus (MRSA) screening and new operational guidance has instructed that all day-case surgical patients should be screened from April 2009. We sought to identify the number of MRSA-positive patients in the vascular day-case population over a 1-year period and to profile this cohort in terms of risk-factors for MRSA. We also sought to identify whether the new guidance from the Department of Health (DH) had resulted in increased screening rates. PATIENTS AND METHODS: Electronic records and laboratory culture results were prospectively consulted to identify whether patients had been screened and if MRSA had been isolated. Consideration was given to whether any patients had a delayed discharge or subsequent admission with an MRSA-related complication. RESULTS: Six patients (2.1%) screened MRSA-positive (DH estimate 7%); five were previously known to be MRSA-positive, therefore only 0.36% patients were newly-identified as MRSA-positive. The proportion of patients screened increased from 35% to 72.5% after April 2009, in accordance with DH guidance. Successful decolonisation was proved in two patients (33.3%). CONCLUSIONS: There is dispute with several of the key assumptions behind the DH's impact assessment justifying an expanded MRSA-screening policy. It is not cost-effective to screen all vascular day-case admissions. We recommend selective screening for patients previously identified as MRSA-positive, or considered high risk.

Use of durometry in assessment of venous disease.

OBJECTIVES: Ulceration of the lower limbs is a common debilitating complication of chronic venous hypertension. Detection of preulcerative skin changes would allow for identification of high-risk patients; early active treatment may prevent ulcer formation. METHODS: Patients with isolated venous disease and volunteers attending outpatient clinics underwent assessment of their clinical, aetiological, anatomical and pathological (CEAP) classification. We employed an industrial durometer, an instrument that measures the hardness of metals and plastic, to assess skin induration. The durometer probe was rested perpendicular on their skin 15 cm above the medial malleolus in non-ulcerated tissue, with the patient and limb in recumbency. The average of four measurements was derived. RESULTS: In 107 people, 203 lower limbs (mean age 55.6 years) were assessed. A significant difference in durometry readings was demonstrated between patients with CEAP classes 0, 1 and 2, and those with classes 4, 5 and 6 (P < 0.0005). There was statistically significant evidence that age and CEAP classification correlated with durometry (P < 0.0001). CONCLUSION: Durometry is of potential value in the assessment and monitoring of preulcerative venous disease, and could help to identify high-risk patients. This would assist in the institution of timely and appropriate treatment.

First seizure - to treat or not to treat?

BACKGROUND: The decision on whether or not to treat a first seizure is dependent on several medical and non-medical factors. AIMS: In this review, we have summarised the important aspects that determine the advantages and disadvantages of treating a first seizure. We have looked at evidence from randomised controlled trials and key observational studies. CONCLUSIONS: There is no randomised controlled evidence that treating the aetiology of a first acute symptomatic seizure reduces the risk of relapse, although there are good biological arguments for this. For first unprovoked seizures, immediate treatment reduces the risk of seizure recurrence in the short term, but does not change the long-term prognosis for epilepsy. Other important considerations include the potential adverse events of antiepileptic drugs and socioeconomic factor such as lifestyle changes, driving, employment, financial implications and relationships. Treatment decisions can be made only on an individual patient basis after weighing the pros and cons of each case separately.

An association between type 1 diabetes and idiopathic generalized epilepsy.

OBJECTIVE: Idiopathic generalized epilepsies (IGEs) account for approximately 30% of all patients with epilepsy. Both the IGEs and type 1 diabetes mellitus (T1D) represent serious worldwide problems, because of related medical and social management costs. Clinical experience suggested the two conditions were seen in individuals more frequently than might be expected by chance. METHODS: We compared the population prevalence of T1D in 15- to 30-year-olds to a cohort of 518 15- to 30-year-olds with IGE. RESULTS: We found a highly significant excess of T1D in our IGE cohort, with an odds ratio of 4.4 (95% confidence interval, 2.1-9.2). INTERPRETATION: Our results suggest that the prevalence of T1D is increased by a factor of four in young adults with IGE. To our knowledge, this is the first published association between the two conditions and expands the diseases known to be associated with T1D.

Epilepsy in the UK: misdiagnosis, mistreatment, and undertreatment? The Wrexham area epilepsy project.

OBJECTIVE: To assess the diagnostic and therapeutic difficulties in patients with epilepsy who had never come into contact with specialist services. METHODS: Assessment was offered to 676 patients diagnosed as having epilepsy and receiving anti-epileptic drug therapy (AED), who had no previous contact with the local epilepsy services. Two hundred and seventy-five patients gave consent and attended for reassessment. We identified the proportion of patients (a) who had previously seen a neurologist, (b) in whom the diagnosis of epilepsy was not secure, (c) in whom planned AED withdrawal could be considered (d) in whom seizure control could be improved. RESULTS: 53/275 (19.3%) of those attending for review had previously been seen by a neurologist. 87/275 (31.6%) patients ultimately received continued specialist care. Diagnostic doubt was expressed in 3/53 (5.6%) and 42/222 (18.9%) of patients diagnosed by neurologist and non-specialist, respectively. Of 133/219 (60.7%) of patients whose epilepsy was in remission, only 6 elected to withdraw or change medication. Of 18 patients with diagnostic doubt who accepted follow-up, 12 successfully stopped treatment. 17/55 (30.9%) patients with active epilepsy (10 partial, 7 generalised) achieved at least a 1 year remission consequent upon treatment in this clinic. In 15 cases this was a first ever remission. CONCLUSION: Approximately 55% of the population of adults receiving treatment for epilepsy have never received specialist advice. Reassessment of these patients uncovers diagnostic uncertainty, failure to classify (leading to sub-optimal therapy) and lack of information and advice about all aspects of epilepsy care. The development of integrated services for people with epilepsy (PWE) must take account of this hidden need. The new General Medical Services contract for general practitioners will bring this need to our attention, and our experience will help predict the measures required to deal with the under-treatent and mistreatment of this group. The majority of PWE, not currently receiving shared care, merit reassessment and approximately one-third will require continued specialist care. Existing services do not have the capacity to process a marked increase in rate of referral. This project informs prioritisation of referrals and service reorganisation.

A comparison of adult onset and "classical" idiopathic generalised epilepsy.

OBJECTIVES: To report the characteristics of a population of patients with idiopathic generalised epilepsy (IGE) with age of onset over 20 years, and compare them with patients with "classical" IGE. METHODS: Data were collected from a computerised database of all patients with IGE attending a regional adult epilepsy clinic. Demographic data, epilepsy characteristics, and treatment outcomes were recorded. RESULTS: 72 patients with IGE of a total population of 844 had an age of onset over 20 years (8.5%). There was similar incidence of family history of epilepsy, EEG findings, and remission rates between those with a younger and older age of onset of IGE. There was a lower incidence of previous febrile convulsions in patients with adult onset. There were fewer patients with absence seizures in the adult onset group (15.3% v 46.4% in the "classical" group). CONCLUSIONS: IGE with onset later than the third decade was rare in the population studied. Prolonged EEG in selected patients may be helpful in diagnosing adult onset IGE, but the diagnosis of epilepsy remains clinical. Adult onset IGE shares many features with "classical" IGE, including EEG findings and prognosis, and is likely to represent a genetic epilepsy.

The relationship between treatment with valproate, lamotrigine, and topiramate and the prognosis of the idiopathic generalised epilepsies.

OBJECTIVE: To examine a large population with idiopathic generalised epilepsy (IGE), and estimate the overall remission rates for the IGEs and subsyndromes in a clinic based sample. Remission rates on valproate, lamotrigine, topiramate, and combinations of these antiepileptic drugs were estimated and factors predicting outcome examined. METHODS: All patients with IGE were identified from a computerised database and EEG records at large adult and paediatric epilepsy clinics. Data were recorded retrospectively on demographics and clinical information, seizure types and syndrome diagnosis, antiepileptic drug treatment details, and remission rates. RESULTS: 54.3% of 962 patients had achieved a one year period of remission; this was most likely with valproate monotherapy (52.1%), with lower rates for lamotrigine and topiramate (16.7% and 34.6%, respectively). The combination of valproate and lamotrigine achieved a remission rate of 15.3%. The factor most predictive of a response to a particular antiepileptic drug regimen was the rank order in which it was given. Relapse rate was high (79.9%) after antiepileptic drug withdrawal in remission, particularly with juvenile myoclonic epilepsy (93.6%). CONCLUSIONS: Valproate may be the most effective antiepileptic drug in the treatment of the IGEs. Combination therapy should be initiated if an adequate trial of valproate monotherapy is not effective, rather than switching to alternative monotherapy. Antiepileptic drug treatment needs to be lifelong in many adult patients with IGE.

The legacy of vigabatrin in a regional epilepsy clinic.

OBJECTIVES: To review all patients who had received vigabatrin at the Walton Centre to determine the incidence of visual field defect, seizure outcome if vigabatrin had been stopped, and adherence to guidelines on the use of vigabatrin in clinical practice. METHODS: Retrospective review of 583 patients prescribed vigabatrin at any time between 1989 and 2001 from a regional and satellite epilepsy clinic. Data were collected on dose and duration of treatment, results of quantitative perimetry, and reasons for, and outcome of, discontinuation. RESULTS: The visual fields were abnormal with no alternative cause in 42 of the 98 tested (43%). There was no clear relation between the cumulative dose of vigabatrin received and the occurrence of a visual field abnormality. Fifty patients continued taking vigabatrin, and a further 84 were lost to follow up while taking vigabatrin. In 75 patients who had stopped vigabatrin due to a visual field abnormality or concern over this potential adverse effect, the seizure control was no different or had improved in 66 (88%), while it had deteriorated in only 7 (9%). CONCLUSIONS: This study confirms the previously reported high incidence of asymptomatic visual field defects associated with vigabatrin. Many patients taking vigabatrin may not have been counselled about the risks, and there are significant cost implications in tracing and assessing those patients lost to follow up. Switching over to another antiepileptic drug usually does not result in deterioration in seizure control, but in clinical practice an individual risk to benefit ratio needs to be taken into consideration.

Future prospects for the drug treatment of epilepsy.

Great progress has been made in the last 150 years in the pharmacological management of epilepsy, and, despite the increasing number of technological advances available, antiepileptic drugs (AEDs) remain the mainstay of treatment for the vast majority of patients with epilepsy. This review looks at possible avenues of development in the drug treatment of epilepsy. The strengths and weaknesses of those AEDs which are currently licensed are examined, and ways in which their use may be improved are discussed (e.g. rational combinations, use of new formulations). Potentially new targets that may allow the development of effective treatments are highlighted (neuroimmunological manipulation, decreasing inherent drug resistance mechanisms, and modification of adenosine neurotransmission), and a summary of the most promising AEDs currently in development is provided [e.g. carabersat, ganaxolone, harkoseride, MDL 27192, safinamide (NW 1015), pregabalin, retigabine, talampanel, valrocemide, losigamone and BIA 2093].

Evaluation of a brief multiple-stimulus preference assessment in a naturalistic context.

We evaluated a brief multiple-stimulus preference assessment within the context of an early intervention program for 3 children who had been diagnosed with autism. Subsequent curriculum-based reinforcer evaluations confirmed the predictions of the preference assessments. In addition, eight additional preference assessments that were conducted over a period of 1 month indicated generally stable preferences for 2 of the 3 participants.

Brown-Vialetto-Van Laere syndrome: case report and literature review.

We describe a case of the Brown-Vialetto-Van Laere syndrome, which is a rare disorder characterized by progressive pontobulbar palsy associated with sensorineural deafness. More than 30 cases have been reported since the first case was described in 1894. We review the literature of this condition, comparing our case with those reported in the literature and emphasizing important features to improve our understanding of this syndrome.

Clinical associations of lymphopenia in elderly persons admitted to acute medical and psychiatric wards.

Lymphopenia is a common finding in old people admitted to medical and psychiatric wards. We describe a pilot study of the clinical associations, and prognostic significance of lymphopenia in elderly persons admitted to acute medical and psychiatric wards. Consecutive patients admitted to acute medical and psychiatric wards were prospectively selected according to initial peripheral lymphocyte count (PLC) into lymphopenic (PLC < 1.0 X 10(9)/litre, n = 41), and non-lymphopenic (PLC > 1.5 x 10(9)/litre, n = 23). Results of routine haematological and biochemical investigations were recorded, as well as drug history and medical diagnoses. Anthropometric measurements, assessment of functional ability (Barthel ADL Index), and cognitive function (Mini-Mental State Examination) were then performed by investigators blind to lymphocyte status. Patients were contacted between 3 and 6 months following recruitment into the study. Lymphopenia was associated with functional ability as measured by a lower Barthel score (p = 0.004), and cognitive impairment as measured by the Mini-Mental State Examination (p = 0.02). No association was found with medical diagnostic groupings, drugs known to cause lymphopenia, nutritional status, or survival. Lymphopenia may be a significant marker of vulnerability, and a larger study is required to elucidate the veracity and mechanisms of lymphopenia-associated debility.

Adenovirus-mediated beta-galactosidase gene delivery to the liver leads to protein deposition in kidney glomeruli.

The many cell types of the kidney, precisely arranged, allow this organ to perform its complex physiologic functions. However, this architectural complexity makes gene transfer into the kidney difficult. One approach to delivering a therapeutic protein to the kidney is to transfer a gene to a non-renal tissue. Release of the protein into the circulation might then result in deposition in the kidney, if the protein has the appropriate molecular properties. In this study, we found that parenterally administered replication deficient adenovirus carrying the beta-galactosidase gene resulted in intense beta-galactosidase gene expression in hepatocytes. As a result of immune attack on transduced hepatocytes, beta-galactosidase protein from these cells is released into the circulation, transported, and deposited almost exclusively in kidney glomeruli. Intense beta-galactosidase activity was noted in both kidneys with a peak at two weeks following viral administration, concurrent with loss of beta-galactosidase positive hepatocytes. Consistent with our hypothesis of protein transfer, no beta-galactosidase mRNA was detected in glomeruli. Moreover, systemically administered protein generated similar glomerular beta-galactosidase activity. Finally, co-administration of murine CTLA4 Ig, an immunomodulator of T cell activation, with the adenovirus protected infected hepatocytes and markedly diminished glomerular beta-galactosidase activity. Collectively, these findings suggest that a therapeutic protein can be "targeted" to the renal glomerulus, utilizing the liver as a gene transfer organ.

Suppression of collagen-induced arthritis through adenovirus-mediated transfer of a modified tumor necrosis factor alpha receptor gene.

OBJECTIVE: To evaluate the efficacy of systemic and intraarticular adenoviral transfer of a modified tumor necrosis factor alpha receptor (TNF alphaR) gene and its expression in rat collagen-induced arthritis (CIA). METHODS: Rats with CIA received injections of replication-deficient adenovirus containing either a TNF alpha inhibitor (TNFI) gene or a control beta-galactosidase (beta-gal) gene. The TNFI gene codes for a fusion protein consisting of the human 55-kd TNF alphaR and a mouse IgG heavy chain. Successful gene transfer was determined by serum TNF alphaR measurements and by histologic examination of injected joints with in situ blue staining. RESULTS: Serum TNF alphaR levels were detectable for 8 days following systemic TNFI gene transfer. CIA severity was significantly suppressed by TNFI gene transfer, both prior to and following arthritis onset (P = 0.0001, by repeated-measures 2-factor analysis of variance). Direct synovial TNFI gene transfer was successful, but induced an inflammatory response without any net TNFI benefit. CONCLUSION: Systemic adenoviral-mediated transfer of the TNFI gene suppressed CIA during its transitory expression. Intraarticular gene transfer was limited by an adenoviral synovitis that was not overcome by delivery of the TNFI gene. TNFI is an excellent protein candidate for further therapeutic study.

Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after Systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts.

Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a limited number of tissues, predominantly activated T lymphocytes. We describe the construction and biological activity of a replication-deficient type-5 adenovirus encoding murine FasL under the control of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with adCMV-FasL-infected COS cells. Systemic administration of adCMV-FasL to Wistar rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose-dependent manner within 72 hr, an effect not seen in lpr mice, or animals administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform primary nonfunction when transplanted into syngeneic or allogeneic diabetic recipients. These results indicate that adCMV-FasL is a potentially useful tool to study Fas/FasL biology.

In vivo adenovirus-mediated gene transfer into normal and cystic rat kidneys.

Gene transfer into the mammalian kidney has proved difficult because of the structural complexity of the organ and its low mitotic index. This article describes the use of intra-arterially injected adenovirus to study gene transfer into the rat kidney in vivo. By pre-chilling the kidney, and incubating the virus with the kidney in the cold for extended periods of time, we were able to successfully transfer a beta-galactosidase (beta-gal) reporter gene into the vasculature without ischemic injury to the kidney. Transfer occurred largely in the cortex when cold was used alone, whereas with the use of cold and vasodilators, transfer was accomplished into the outer medulla in both the inner and outer stripes. In the Han:SPRD rat model of autosomal dominant polycystic kidney disease (ADPKD), gene transfer occurred into the vasculature, some epithelial cysts and interstitial cells. This is the first description of substantial in vivo gene transfer into both normal and cystic kidneys. The methodology could find application in the creation of new models of renal disease, for in vivo therapeutic intervention or for genetic modification of an allograft at the time of harvest.