Anxiety and depression in two indigenous communities in Bangladesh.

BACKGROUND: The mental health status of indigenous people in Bangladesh has attracted little or no attention. The objective of the present study is to determine the extent of symptoms of anxiety and depression in the two largest indigenous communities in Bangladesh. METHODS: In total, 240 participants were recruited, 120 from each of the Marma and Chakma communities with an overall mean age of 44.09 years (s.d. 15.73). Marma people were older (mean ages 48.92 v. 39.25, p < 0.001). Participants completed the Anxiety Scale (AS) and Depression Scale (DS) that have been developed and standardised in Bangladesh in the Bangla (Bengali) language. RESULTS: Results indicated that anxiety and depression scores were elevated in both communities, 59.2% of the participants scoring above the cut-off for clinical significance on AS and 58.8% of the participants scoring above the cut-off for clinical significance on DS. Marma people compared to Chakma people were more anxious (M = 59.49 v. 43.00, p < 0.001) and more depressed (M = 106.78 v. 82.30, p < 0.001). The demographic variables of age, sex and socioeconomic status were weakly or inconsistently related to scores. In the Marma people, females scored higher on both AS and DS, but in the Chakma community, males scored higher on AS and the same on DS. CONCLUSION: The finding of significant anxiety and depression in communities with such limited mental health services is a matter of concern and emphasises the need to formulate and implement appropriate mental health policies for indigenous people in Bangladesh and other parts of the world.

Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.

BACKGROUND: Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD. METHODS: We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019. RESULTS: We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes. CONCLUSIONS: In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities. TRIAL REGISTRATION: PROSPERO CRD42019123088.

Trends in antiepileptic drug treatment and effectiveness in clinical practice in England from 2003 to 2016: a retrospective cohort study using electronic medical records.

OBJECTIVE: To assess the evolution of antiepileptic drug (AED) treatment patterns and seizure outcomes in England from 2003 to 2016. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of electronic medical records from Clinical Practice Research Datalink and National Health Service Digital Hospital Episode Statistics databases. Patients newly diagnosed with epilepsy were identified and followed until end of data availability. Three eras were defined starting 1 April 2003 (first National Institute for Health and Care Excellence (NICE) guideline); 1 September 2007 (Standard and New Antiepileptic Drugs publication); and 1 January 2012 (second NICE guideline). OUTCOME MEASURES: Time from diagnosis to first AED; AED sequence; time from first AED to first 1-year remission period (no new AED attempts and no seizure-related healthcare events); time from first AED to refractoriness (third AED attempt regardless of reason); Kaplan-Meier analysis of time-to-event variables. RESULTS: 4388 patients were included (mean follow-up: 6.8, 4.2 and 1.7 years by era). 84.6% of adults (≥16 years), 75.5% of children (<16) and 89.1% of elderly subgroup (65+) received treatment within 1 year; rates were generally stable over time. Treatment trends included reduced use of carbamazepine (adult first line, era 1: 34.9%; era 3: 10.7%) and phenytoin, earlier line and increased use of levetiracetam (adult first line, era 1: 2.6%; era 3: 26.2%) and lamotrigine (particularly in adults and elderly subgroup), and a larger number of different AEDs used. Valproate use shifted somewhat to later lines. Rates of 1-year remission within 2 years of starting treatment increased in adults (era 1: 71.9%; era 3: 81.4%) and elderly (era 1: 76.1%; era 3: 81.7%). Overall, 55.5% of patients relapsed after achieving 1-year remission. Refractoriness rates remained stable over time (~26% of adults within 5 years). CONCLUSION: Treatment trends often were not aligned with era-relevant guidance. However, our results suggest a slight improvement in epilepsy treatment outcomes over the 13-year period.

Sulthiame add-on therapy for epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2015, Issue 10. Epilepsy is a common neurological condition, characterised by recurrent seizures. Most people respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures, despite treatment with multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy. OBJECTIVES: To assess the efficacy and tolerability of sulthiame as add-on therapy for people with epilepsy of any aetiology compared with placebo or another antiepileptic drug. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and CENTRAL (17 January 2019), MEDLINE Ovid (1946 to January 16, 2019), ClinicalTrials.gov and the WHO ICTRP Search Portal (17 January 2019). We imposed no language restrictions. We contacted the manufacturers of sulthiame, and researchers in the field to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled trials of add-on sulthiame, with any level of blinding (single, double or unblinded) in people of any age, with epilepsy of any aetiology. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and extracted relevant data. We assessed these outcomes: (1) 50% or greater reduction in seizure frequency between baseline and end of follow-up; (2) complete cessation of seizures during follow-up; (3) mean seizure frequency; (4) time-to-treatment withdrawal; (5) adverse effects; and (6) quality of life. We used intention-to-treat for primary analyses. We presented results as risk ratios (RR) with 95% confidence intervals (CIs). However, due to the paucity of trials, we mainly conducted a narrative analysis. MAIN RESULTS: We included one placebo-controlled trial that recruited 37 infants with newly diagnosed West syndrome. This trial was funded by DESITIN Pharma, Germany. During the study, sulthiame was given as an add-on therapy to pyridoxine. No data were reported for the outcomes: 50% or greater reduction in seizure frequency between baseline and end of follow-up; mean seizure frequency; or quality of life. For complete cessation of seizures during a nine-day follow-up period for add-on sulthiame versus placebo, the RR was 11.14 (95% CI 0.67 to 184.47; very low-certainty evidence), however, this difference was not shown to be statistically significant (P = 0.09). The number of infants experiencing one or more adverse events was not significantly different between the two treatment groups (RR 0.85, 95% CI 0.44 to 1.64; very low-certainty evidence; P = 0.63). Somnolence was more prevalent amongst infants randomised to add-on sulthiame compared to placebo, but again, the difference was not statistically significant (RR 3.40, 95% CI 0.42 to 27.59; very low-certainty evidence; P = 0.25). We were unable to conduct meaningful analysis of time-to-treatment withdrawal and adverse effects due to incomplete data. AUTHORS' CONCLUSIONS: Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in infants with West syndrome, however, we are very uncertain about the reliability of this finding. The included study was small and had a significant risk of bias, largely due to the lack of details regarding blinding and the incomplete reporting of outcomes. Both issues negatively impacted the certainty of the evidence. No conclusions can be drawn about the occurrence of adverse effects, change in quality of life, or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in people with epilepsy outside West syndrome.Large, multi-centre randomised controlled trials are needed to inform clinical practice, if sulthiame is to be used as an add-on therapy for epilepsy.

The overlap between epilepsy and Alzheimer's disease and the consequences for treatment.

Introduction: Alzheimer's disease may be associated with both clinical and subclinical epileptic seizure activity. Once regarded as an epiphenomenon, epileptiform activity may, in fact, be an integral part of the Alzheimer's phenotype, and may be not only a symptomatic therapeutic target but also a possible mechanism to retard or prevent disease progression. Areas covered: The authors review clinical research articles with a focus on the semiology, epidemiology, and treatment of seizures in Alzheimer's disease, and also look at some experimental animal model studies which have informed clinical thinking on seizure aetiopathogenesis. The evidence base for treatment decisions is sparse. A brief overview of the clinical assessment of Alzheimer's disease patients considering relevant differential diagnoses and diagnostic pitfalls is presented. Expert opinion: Studies of epileptic seizures in Alzheimer's disease have become more frequent over the last 5-10 years. Understanding of seizure semiology, epidemiology, and possible pathogenesis has increased. However, the optimal management of seizures in this context remains unknown, largely due to the paucity of studies sufficient to examine this question. Clearly, such studies will be required, not only to inform clinicians about symptomatic control of seizures in Alzheimer's disease but also to investigate whether this might impact on disease progression.

Breakthrough seizures-Further analysis of the Standard versus New Antiepileptic Drugs (SANAD) study.

OBJECTIVES: To develop prognostic models for risk of a breakthrough seizure, risk of seizure recurrence after a breakthrough seizure, and likelihood of achieving 12-month remission following a breakthrough seizure. A breakthrough seizure is one that occurs following at least 12 months remission whilst on treatment. METHODS: We analysed data from the SANAD study. This long-term randomised trial compared treatments for participants with newly diagnosed epilepsy. Multivariable Cox models investigated how clinical factors affect the probability of each outcome. Best fitting multivariable models were produced with variable reduction by Akaike's Information Criterion. Risks associated with combinations of risk factors were calculated from each multivariable model. RESULTS: Significant factors in the multivariable model for risk of a breakthrough seizure following 12-month remission were number of tonic-clonic seizures by achievement of 12-month remission, time taken to achieve 12-month remission, and neurological insult. Significant factors in the model for risk of seizure recurrence following a breakthrough seizure were total number of drugs attempted to achieve 12-month remission, time to achieve 12-month remission prior to breakthrough seizure, and breakthrough seizure treatment decision. Significant factors in the model for likelihood of achieving 12-month remission after a breakthrough seizure were gender, age at breakthrough seizure, time to achieve 12-month remission prior to breakthrough, and breakthrough seizure treatment decision. CONCLUSIONS: This is the first analysis to consider risk of a breakthrough seizure and subsequent outcomes. The described models can be used to identify people most likely to have a breakthrough seizure, a seizure recurrence following a breakthrough seizure, and to achieve 12-month remission following a breakthrough seizure. The results suggest that focussing on achieving 12-month remission swiftly represents the best therapeutic aim to reduce the risk of a breakthrough seizure and subsequent negative outcomes. This will aid individual patient risk stratification and the design of future epilepsy trials.

Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.

BACKGROUND: Carbamazepine (CBZ) is a commonly used drug for epilepsy that is associated with troublesome adverse events including dizziness, double vision, drowsiness, poor co-ordination and unsteadiness. These adverse events often occur during peaks in drug plasma concentration. These adverse events may limit the daily dose of CBZ that can be tolerated and reduce the chances of seizure control in patients who require high doses. A controlled-release formulation of CBZ delivers the same dose over a longer period of time when compared to a standard immediate-release formulation, thereby reducing post-dose peaks in CBZ plasma concentration and potentially reducing adverse events.This is an updated version of the original Cochrane review published in Issue 12, 2014. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy.The following review questions were investigated.(1) For newly diagnosed patients commencing CBZ, how do IR and CR formulations compare for efficacy and tolerability?(2) For patients on established treatment with IR CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and the tolerability of a switch to a CR formulation versus remaining on the IR formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register, CENTRAL, and MEDLINE (Ovid) from inception to 30 August 2016. SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures included measures of seizure frequency, incidence of adverse events, proportion of patients with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted the data and recorded relevant information on a standardised data extraction form. We used the Cochrane risk of bias tool to assess the methodological quality of included studies.The heterogeneity of the included trials with respect to the reporting of outcomes resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials (296 participants) fulfilled the criteria for inclusion in this review. Only one study had a low risk of bias. Two studies had a high risk of bias and the rest of the studies were rated as unclear risk of bias. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference in adverse events, and another trial reported more adverse events in the CR CBZ group than the IR CBZ group, although the increase was not statistically significant. AUTHORS' CONCLUSIONS: For this update no new eligible studies were identified and the conclusions drawn from the initial review remain unchanged.At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size and of poor methodological quality limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.

Advanced nodal stage predicts venous thromboembolism in patients with locally advanced non-small cell lung cancer.

OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) are known to be at high risk for venous thromboembolism (VTE), but previous studies have not specifically analyzed locally advanced disease. We performed a retrospective VTE risk analysis in a cohort of locally advanced NSCLC treated with definitive intent including radiation therapy. MATERIALS AND METHODS: The cohort consisted of 629 patients with stage II-III NSCLC treated at a single institution from January 2003 to December 2012. All patients received treatment with curative intent, including radiation therapy. Fine and Gray's competing-risks regression model, accounting for death and distant metastasis as competing risks, was used to identify significant predictors of VTE risk, and cumulative incidence estimates were generated using the competing-risks model. RESULTS AND CONCLUSION: At a median follow-up of 31 months, 127 patients developed a VTE, with 80% of events occurring in the first year after treatment initiation. 1-year and 3-year overall cumulative incidence estimates were 13.5% and 15.4%, respectively. On univariate analysis, stage IIIB and N3 nodal disease were associated with increased VTE risk. In the final multivariable model, N3 nodal disease was associated with increased VTE risk (Hazard ratio 1.64; 95% CI 1.06-2.54; p=0.027). In conclusion, patients with locally advanced NSCLC are at high risk for VTE, especially in the first year after treatment initiation, with a 1-year cumulative incidence of 13.5%. N3 nodal staging was associated with significantly higher VTE risk compared to N0-N2 staging.

Sulthiame add-on therapy for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition characterised by recurrent seizures. Most patients respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures despite multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy. OBJECTIVES: To compare the efficacy and side-effect profile of sulthiame as add-on therapy compared with placebo or another antiepileptic drug. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, ClinicalTrials.gov and the WHO ICTRP Search Portal on 11 August 2015. No language restrictions were imposed. We contacted the manufacturers of sulthiame and researchers in the field to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled add-on trials of sulthiame in people of any age with epilepsy of any aetiology. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 1) reduction in seizure frequency of 50% or greater between baseline and end of follow-up; 2) complete cessation of seizures during follow-up; 3) mean seizure frequency; 4) time to treatment withdrawal; 5) adverse drug effects; and 6) quality of life scoring. Primary analyses were intention-to-treat. We present a narrative analysis. MAIN RESULTS: We included one trial with 37 participants with a new diagnosis of West syndrome. Sulthiame was given as an add-on therapy to pyridoxine. No data were reported for outcomes 1), 3) or 6). Overall risk ratio with 95% confidence intervals (CI) for complete cessation of seizures during a nine-day follow-up period versus placebo was 0.71 (95% CI 0.53 to 0.96). Meaningful analysis of time to treatment withdrawal and adverse drug effects was not possible due to incomplete data. AUTHORS' CONCLUSIONS: Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in patients with West syndrome. The included study was small and had a significant risk of bias which limits the impact of the evidence. No conclusions can be drawn about the occurrence of adverse drug effects, change in quality of life or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in patients with epilepsy outside West syndrome. Large, multi-centre randomized controlled trials are necessary to inform clinical practice if sulthiame is to be used as an add-on therapy for epilepsy.

Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

AIM: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. METHODS: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. RESULTS: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. CONCLUSION: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.

Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.

BACKGROUND: Epilepsy is defined as the tendency to spontaneous, excessive neuronal discharge manifesting as seizures. It is a common disorder with an incidence of 50 per 100,000 per year and a prevalence of 0.5% to 1% in the developed world (Hauser 1993).Carbamazepine (CBZ) is a widely used antiepileptic drug that is associated with a number of troublesome adverse events including dizziness, double vision and unsteadiness. These often occur during peaks in drug plasma concentration. The occurrence of such adverse events may limit the daily dose that can be tolerated and reduce the chances of seizure control for patients requiring higher doses (Vojvodic 2002). A controlled-release formulation of carbamazepine delivers the same dose over a longer period of time when compared to a standard formulation, thereby reducing post-dose peaks and potentially reducing adverse events associated with peak plasma levels. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy.The following review questions were investigated.(1) For newly diagnosed patients commencing CBZ, how do IR and CR formulations compare for efficacy and tolerability?(2) For patients on established treatment with IR CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and the tolerability of a switch to a CR formulation versus remaining on the IR formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (10 November 2014), Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO) 11 November 2014, and MEDLINE (Ovid, 1946 to 11 November 2014). SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures include seizure frequency, incidence of adverse events, proportion of patients with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed with respect to study design, type of control, method and concealment of allocation, blinding and completeness of follow up, and the presence of blinding for assessment of non-fatal outcomes. We did not make use of an overall quality score.Two review authors (GP, MS) independently extracted the data and recorded relevant information on a standardised data extraction form. The trials were assessed for inclusion.The heterogeneity of the included trials resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials fulfilled the criteria for inclusion in this review. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference, with a further trial reporting increased adverse events in the CR CBZ group although the increase was not statistically significant. AUTHORS' CONCLUSIONS: At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size, had poor methodological quality and possessed a high risk of bias, limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.

Sulthiame monotherapy for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we present a summary of evidence for the use of STM as monotherapy in epilepsy. OBJECTIVES: To examine the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (24 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE Ovid (1946 to 24 October 2013), SCOPUS (1823 to 24 October 2013), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (28 October 2013) and ClinicalTrials.gov (28 October 2013). We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data.The following outcomes were assessed: (1) time to treatment failure; (2) time to 12-month remission; (3) proportion seizure free at 12 months; (4) adverse effects; and (5) quality of life scoring. Primary analyses were intention-to-treat when possible. A narrative analysis of the data was presented. MAIN RESULTS: Two studies representing 100 participants with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS) and one study representing 146 participants with a diagnosis of generalised tonic-clonic seizures (GTCS) were included. STM was given as monotherapy compared with placebo in the BECTS studies and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. No data were reported for outcome (1), (2), (3) or (5). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than were participants receiving phenytoin in the GTCS study (risk ratio (RR) 0.03, 95% confidence interval (CI) 0.00 to 0.58). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. Two ongoing studies comparing STM monotherapy versus placebo or levetiracetam in BECTS were identified. AUTHORS' CONCLUSIONS: Small sample size, poor methodological quality and lack of data on important outcome measures prevent any meaningful conclusions regarding the efficacy and safety of sulthiame as monotherapy in epilepsy.

Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.

BACKGROUND: Epilepsy is defined as the tendency to spontaneous, excessive neuronal discharge manifesting as seizures. It is a common disorder with an incidence of 50 per 100,000 per year and a prevalence of 0.5% to 1% (Hauser 1993) in the developed world.Carbamazepine (CBZ) is a widely used antiepileptic drug that is associated with a number of troublesome adverse events including dizziness, double vision and unsteadiness. These often occur during peaks in plasma concentration. The occurrence of such adverse events may limit the daily dose that can be tolerated and reduce the chances of seizure control for patients requiring higher doses (Vojvodic 2002). A controlled-release formulation of carbamazepine delivers the same dose over a longer period of time when compared to a standard formulation, thereby reducing post-dose peaks and potentially reducing adverse events associated with peak plasma levels. OBJECTIVES: To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy. The following hypotheses were tested.(1) For newly diagnosed patients commencing CBZ, how do immediate-release and controlled-release formulations compare for efficacy and tolerability?(2) For patients on established treatment with immediate-release CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and tolerability of a switch to a controlled-release formulation versus remaining on the immediate-release formulation? SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (5 September 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2013) in The Cochrane Library and MEDLINE (1946 to 5 September 2013). SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures include seizure frequency, incidence of adverse events, proportion with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed with respect to study design, type of control, method and the concealment of allocation, blinding and completeness of follow up, and the presence of blinding for assessment of non-fatal outcomes. We did not make use of an overall quality score.Two review authors (GP, MS) independently extracted the data and recorded relevant information on a standardised data extraction form. Results were assessed for inclusion.The heterogeneity of the included trials resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. MAIN RESULTS: Ten trials fulfilled the criteria for inclusion in this review. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference, with a further trial reporting increased adverse events in the CR CBZ group although not statistically significant. AUTHORS' CONCLUSIONS: At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size, poor methodological quality and possessed a high risk of bias, limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.

Sulthiame add-on therapy for epilepsy.

BACKGROUND: Epilepsy is a common neurological condition characterised by recurrent seizures. Most patients respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures despite multiple antiepileptic drugs. Sulthiame is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy. OBJECTIVES: To compare the efficacy and side-effect profile of sulthiame as add-on therapy compared with placebo or another antiepileptic drug. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and the WHO IRCTRP Search Portal on 28th August 2012. No language restrictions were imposed. We contacted the manufacturers of sulthiame and researchers in the field to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised placebo-controlled add-on trials of sulthiame in people of any age with epilepsy of any aetiology. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (1) reduction in seizure frequency of 50% or greater between baseline and end of follow-up (2) complete cessation of seizures during follow-up (3) mean seizure frequency (4) time to treatment withdrawal (5) adverse drug effects (6) quality of life scoring. Primary analyses were intention-to-treat. Narrative analysis is presented. MAIN RESULTS: One trial was included representing 37 patients with a new diagnosis of West syndrome. Sulthiame was given as an add-on therapy to pyridoxine. No data were reported for outcomes (1), (3) or (6). Overall risk ratio (RR) with 95% confidence intervals (CI) for complete cessation of seizures during a nine-day follow-up period versus placebo was 0.71 (95% CI 0.53 to 0.96). Meaningful analysis of time to treatment withdrawal and adverse drug effects was impossible due to incomplete data. AUTHORS' CONCLUSIONS: Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in patients with West syndrome. The included study was small and had a significant risk of bias which limits the impact of the evidence. No conclusions can be drawn on the occurrence of adverse drug effects, change in quality of life or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in patients with epilepsy outside West syndrome. Large, multi-centre randomised controlled trials are necessary to inform clinical practice if sulthiame is to be used as an add-on therapy for epilepsy.

Improving the diagnosis of central nervous system infections in adults through introduction of a simple lumbar puncture pack.

BACKGROUND: Acute central nervous system (CNS) infections, such as meningitis and encephalitis, are neurological emergencies for which accurate diagnosis and prompt treatment improve the outcome. Analysis of the cerebrospinal fluid (CSF) obtained at lumbar puncture (LP) is pivotal to establishing the diagnosis and guiding management. PCR analysis of the CSF is an important method to identify the pathogen. However, recent studies have demonstrated that many patients have inadequate CSF sample collection and analysis. AIMS: To increase the proportion of patients having an LP for a suspected CNS infection for whom the appropriate samples are taken. Secondary aims included to increase the proportion of patients for whom a pathogen was identified. METHODS: The authors developed an LP pack for patients with a suspected CNS infection. They also assessed its impact on diagnosis by comparing practice 6 months before and after its introduction to the medical admissions unit of a large inner city teaching hospital. RESULTS: The authors found that the LP pack reduced major errors in CSF sample collection and improved the diagnosis of acute CNS infections; among those patients who had a CSF pleocytosis, the proportion with a viral or bacterial pathogen identified by PCR was increased after introduction of the pack. DISCUSSION: This study has demonstrated that the introduction of a simple low-cost LP pack into a busy acute medical setting can improve the diagnosis of CNS infections and, thus, guide treatment. Further work is needed to see if these results are more widely reproducible, and to examine the clinical, health and economic impact on overall management of patients with suspected CNS infections.

Reporting of adverse events in randomised controlled trials of antiepileptic drugs using the CONSORT criteria for reporting harms.

PURPOSE: To assess the reporting of adverse events (AEs) in randomised controlled trials (RCTs) of antiepileptic drugs (AEDs) using the CONSORT statement for harms 2004, and to determine if reporting has changed since introduction of this standard. PRINCIPAL RESULTS: One hundred and fifty two RCTs were included from a search of papers published between 1999 and 2008 inclusive. We identified 23 criteria in the CONSORT statements. The mean number of criteria met per trial was 11.3 (95%CI 10.6-12.0). Commercially funded studies met 12.6 and non-commercially funded met 9.4 (p<0.001). Trials recruiting adults met 12.5 and trials recruiting children met 9.3 (p<0.001). Trials published before 2004 met 11.6 and trials published after 2004 met 11.1 (p=0.53). Commercially funded trials met the majority of criteria more than non-commercially sponsored trials, particularly for definition of AEs (RR 3.15, CI 1.67-5.95) and the use of a validated dictionary of terms (RR 3.46, CI 1.41-8.44). Definitions for AEs (RR 2.32, CI 1.07-5.02) and details of analyses (RR 2.05, CI 1.01-4.15) were reported in adult trials more often than trials in children. MAJOR CONCLUSIONS: Reporting of AEs in RCTs of AEDs is poor and has not improved since the publication of the CONSORT guidelines on the reporting of harms. Commercially funded trials were better reported than non-commercially funded trials and trials recruiting adults were better reported than trials recruiting children. These findings have serious implications as poor reporting precludes bias being detected and hinders adequate risk benefit analyses. Journal editors, authors and reviewers should be encouraged to follow current guidance.

Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.

BACKGROUND: Epilepsy is defined as the tendency to spontaneous, excessive neuronal discharge, manifesting as seizures. It is a common disorder with an incidence of 50 per 100,000 per year and a prevalence of 0.5% to 1% (Hauser 1993) in the developed world.Carbamazepine is a commonly used antiepileptic drug that is associated with a number of troublesome adverse events including dizziness, double vision and unsteadiness. These often occur during peaks in plasma concentration. The occurrence of such adverse events may limit the daily dose that can be tolerated and reduce the chances of seizure control for patients requiring higher doses (Vojvodic 2002). A controlled-release formulation of carbamazepine delivers the same dose over a longer period of time when compared to a standard formulation, thereby reducing post-dose peaks and potentially reducing adverse events associated with peak plasma levels. OBJECTIVES: To determine the efficacy of immediate-release carbamazepine (IR CBZ) versus controlled-release carbamazepine (CR CBZ) in patients with newly diagnosed epilepsy.To determine the efficacy of switching to CR CBZ in patients treated with IR CBZ but experiencing unacceptable adverse events. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialised Register (25 September 2009), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), and MEDLINE (1950 to September week 3, 2009). SELECTION CRITERIA: Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures include seizure frequency, incidence of adverse events, proportions with treatment failure and quality of life measures. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed with respect to study design, type of control, method and concealment of allocation, blinding and completeness of follow up, and the presence of blinding for assessment of non-fatal outcomes. We did not make use of an overall quality score.Two review authors (GP, MS) independently extracted the data and recorded relevant information on a standardised data extraction form. Results were assessed for inclusion.The heterogeneity of the included trials resulted in only a narrative, descriptive analysis being possible for both categorical and time-to-event data. MAIN RESULTS: Ten trials fulfilled the criteria for inclusion in this review. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ, not statistically significant. One trial found no difference, with a further trial reporting increased adverse events in the CR CBZ although not statistically significant. AUTHORS' CONCLUSIONS: At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size, poor methodological quality and possessed a high risk of bias, limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.

Effort testing in contemporary UK neuropsychological practice.

A survey of members of the British Psychological Society Division of Neuropsychology (N = 588) was conducted via email to ascertain current practice with respect to the use of symptom validity testing (SVT) in clinical and legal neuropsychological assessments. Replies were received from 130 practicing neuropsychologists. Results showed that 59% frequently use SVT in legal assessments, but a minority (15%) employ them in clinical assessments. Practice in the UK is only moderately different to that in North America with respect to frequency of use of SVT, although methods employed showed greater diversity. Favored tests, respondents' justifications for use of SVT and rationales for not using SVT are reported.