SUMMARYPurpose: Patients with Alzheimer's disease (AD) have an increased risk of developing seizures or epilepsy. Little is known about the role of risk factors and about the risk of developing seizures/epilepsy in patients with vascular dementia (VD). The aim of this study was to assess incidence rates (IRs) of seizures/epilepsy in patients with AD, VD, or without dementia, and to identify potential risk factors of seizures or epilepsy. Methods: We conducted a follow-up study with a nested case-control analysis using the United Kingdom-based General Practice Research Database (GPRD). We identified patients aged ‡65 years with an incident diagnosis of AD or VD between 1998 and 2008 and a matched comparison group of dementia-free patients. Conditional logistic regression was used to estimate the odds ratio (OR) with a 95% confidence interval (CI) of developing seizures/ epilepsy in patients with AD or VD, stratified by age at onset and duration of dementia as well as by use of antidementia drugs. Key Findings: Among 7,086 cases with AD, 4,438 with VD, and 11,524 matched dementia-free patients, we identified 180 cases with an incident diagnosis of seizures/epilepsy. The IRs of epilepsy/seizures for patients with AD or VD were 5.6/1,000 person-years (py) (95% CI 4.6-6.9) and 7.5/ 1,000 py (95% CI 5.7-9.7), respectively, and 0.8/1,000 py (95% CI 0.6-1.1) in the dementia-free group. In the nested case-control analysis, patients with longer standing ( ‡3 years) AD had a slightly higher risk of developing seizures or epilepsy than those with a shorter disease duration, whereas in patients with VD the contrary was observed. Significance: Seizures or epilepsy were substantially more common in patients with AD and VD than in dementiafree patients. The role of disease duration as a risk factor for seizures/epilepsy seems to differ between AD and VD.

Background: This study estimated the risk of infection-related hospitalizations and death in patients with and without multiple sclerosis (MS). Methods: We identified adults with MS in the US Department of Veterans Affairs (VA) system between 1999 and 2010. Each veteran with MS was matched, on age and sex, with up to four veterans without MS. Multivariable Cox proportional hazards regression models were performed to assess the influence of MS on the development of serious and fatal infections. Results: The cohort included 7743 veterans with MS and 30,972 veterans without MS. Mean (SD) age was 53.8 (13.3) years, and 80.8% were male. The incidence per 1000 person-years of overall serious infections was 19.2 (95% confidence interval [CI], 17.6–20.8) for those with MS and 10.3 (95% CI, 9.8–10.9) for those without MS. Fatal infection incidence rates were 1.2 (95% CI, 0.8–1.7) for patients with MS and 0.5 (95% CI, 0.3–0.6) for patients without MS. Regression models showed that veterans with MS were at greater risk for overall serious (hazard ratio [HR] = 1.52, P < .01) and fatal (HR = 1.85, P = .03) infections and serious respiratory (HR = 1.31, P = .01), urinary tract (HR = 4.44, P < .01), and sepsis-related infections (HR = 2.56, P < .01). Conclusions: This study provides evidence that VA patients with MS are more likely than those without MS to be hospitalized and die of infection.

SUMMARYObjective: The annual prevalence of antiepileptic drug (AED) prescribing reported in the literature differs considerably among European countries due to use of different type of data sources, time periods, population distribution, and methodologic differences. This study aimed to measure prevalence of AED prescribing across seven European routine health care databases in Spain, Denmark, The Netherlands, the United Kingdom, and Germany using a standardized methodology and to investigate sources of variation. Methods: Analyses on the annual prevalence of AEDs were stratified by sex, age, and AED. Overall prevalences were standardized to the European 2008 reference population. Results: Prevalence of any AED varied from 88 per 10,000 persons (The Netherlands) to 144 per 10,000 in Spain and Denmark in 2001. In all databases, prevalence increased linearly: from 6% in Denmark to 15% in Spain each year since 2001. This increase could be attributed entirely to an increase in "new," recently marketed AEDs while prevalence of AEDs that have been available since the mid-1990s, hardly changed. AED use increased with age for both female and male patients up to the ages of 80 to 89 years old and tended to be somewhat higher in female than in male patients between the ages of 40 and 70. No differences between databases in the number of AEDs used simultaneously by a patient were found. Significance: We showed that during the study period of 2001-2009, AED prescribing increased in five European Union (EU) countries and that this increase was due entirely to the newer AEDs marketed since the 1990s. Using a standardized methodology, we showed consistent trends across databases and countries over time. Differences in age and sex distribution explained only part of the variation between countries. Therefore, remaining variation in AED use must originate from other differences in national health care systems.

Patients with VD, but not AD, have a markedly higher risk of developing an ischemic stroke than those without dementia. In patients with AD, but not VD, use of atypical antipsychotic drugs was associated with an increased risk of TIA.

Purpose The purpose of this study is to quantify the impact of the different outcomes and definitions of suicidality on the association between antiepileptic drugs (AEDs) and suicidality. Methods Retrospective cohort studies of selected AEDs (carbamazepine, gabapentin, lamotrigine, phenytoin, pregabalin, topiramate and valproate) using data from UK Clinical Practice Research Datalink (CPRD) alone and linked to UK Hospital Episode Statistics (HES) and UK Office of National Statistics (ONS), and from Danish national registries (DNR). Follow-up started at initiation of one of the study AEDs, divided into exposure periods, a maximum 90-day post-exposure period, and the reference period starting the day after the 90-day postexposure period ended. Primary outcomes were completed suicide (SUI)/suicide attempt (SA) for CPRD and SUI/deliberate self-harm (DSH) for DNR. We applied adjusted Cox regression analyses and sensitivity analyses with varying outcome definitions. Results We analyzed 84 524 AED users from CPRD-HES-ONS (1188 SUI/SA; 96 SUI) and 258 180 users from DNR (7561 SUI/DSH; 781 SUI). The adjusted hazard ratios (HRs) on SUI/SA ranged between 1.3 (95% confidence interval (CI): 0.84-2.00) for lamotrigine and 2.7 (1.24-5.81) for phenytoin in CPRD-HES-ONS, and between 0.9 (0.78-1.00) for valproate and 1.8 (1.10-3.07) for phenytoin on SUI/DSH in DNR. HRs for the primary outcomes varied consistently across exposure periods and data sources. HRs for SUI were in general lower, more stable and similar for periods of exposure and the 90-day post-exposure period. Conclusion Applying different outcomes and definitions of suicidality had an impact on the relative risks of suicidality associated with the investigated AEDs with results for SUI being most consistent and reliable.

A79 grams), and male gender. Increasing length of mechanical ventilation and birth weight 500-999 grams were associated with ever receiving inhaled corticosteroids. CONCLUSIONS: Bronchodilator and ICS use are common for infants with BPD at U.S. Children's hospitals, although frequency of use varies significantly. The effectiveness and safety of their use in these infants needs to be determined, in order to develop evidence-based recommendations.

To report the effect of BG-12 (dimethyl fumarate) in reducing the number of relapses requiring intravenous (IV) steroids and multiple sclerosis (MS)-related hospitalizations from a pre-specified integrated analysis of DEFINE and CONFIRM, which was designed to estimate-more precisely-the therapeutic effect of BG-12 versus placebo. METHODS: Eligible patients were aged 18-55 years with relapsing-remitting MS (McDonald criteria) and an Expanded Disability Status Scale score of 0-5.0. Patients who received oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo were included and the integrated analysis was to be conducted only if baseline characteristics and treatment effects were similar between the studies. Numbers of relapses requiring IV steroids and MS-related hospitalizations (tertiary endpoints in DEFINE and CONFIRM) were assessed. RESULTS: The integrated analysis included 769, 761, and 771 patients who received BG-12 BID, TID, and placebo, respectively. Baseline characteristics and treatment effects were generally similar between DEFINE and CONFIRM. There were significantly fewer relapses requiring steroids and MS-related hospitalizations in both BG-12 groups compared with placebo. BG-12 reduced the annualized rate of relapses requiring IV steroids by 48% (BID; rate ratio, 0.52 [95% confidence interval, 0.43-0.64]) and 50% (TID; 0.50 [0.41-0.61]) versus placebo (both p<0.0001) and reduced the annualized rate of MS-related hospitalizations by 34% (BID; 0.66 [0.47-0.92]; p=0.0146) and 47% (TID; 0.53 [0.37-0.75]; p=0.0004) at 2 years. CONCLUSIONS: BG-12 significantly reduced the number of relapses requiring IV steroids and MS-related hospitalizations, which suggests benefits with regard to patient burden and health economic savings due to decreased resource utilization. These findings further support the efficacy results of DEFINE and CONFIRM.