Cognitive Adverse Events Research Articles

Cognitive dysfunction and adverse events during oral anticoagulant: a prospective cohort study

Abstract Background Oral anticoagulants (AC), represent the leading cause of iatrogenic morbimortality in France. AC are widely prescribed among the elderly. The assessment of the cognitive dysfunction (CD) is not included within the common thrombotic and bleeding risk scores. Purpose The objective of this study was to examine an association between CD and adverse events (AE) in patients receiving oral AC. Methods A prospective monocentric cohort study was conducted in patients (≥60 years-old) on oral AC. Death, hemorrhages, falls, hospital readmission, thromboembolic events were collected over 6 months follow-up. Patients were included during an hospitalization for any medical or surgical condition and divided in three groups, according to their Mini Mental State Examination (MMSE): Group 1 (absence of CD) MMSE ≥27, Group 2 (mild CD) 24<mmse<26, >≤MMSE≤26, Group 3 (significant CD) MMSE ≤23. Results Among 120 patients (mean age: 82,2±8,8 years), the all-causes mortality (n=25) was significantly higher in the Group 3 (n=17, p=0,006); this also applies to the incidence of falls (n=34, p=0,009) or major hemorrhages (n=10, p=0,023). There was no thromboembolic event. Minor hemorrhages and hospital readmissions were not different in the 3 groups. Multivariate analysis shows a significant risk of mortality (OR 4.3, (p=0,025, IC [1,20–15,42]) in group 3. Conclusion After 6 months of follow up, the cognitive dysfunction was associated with mortality, major hemorrhages and falls among the elderly receiving oral AC. A systematic assessment of cognitive functions of these patients seems to be essential to analyze the global risk and the risks related to the AC treatment.</mmse<26,> Funding Acknowledgement Type of funding sources: None.

Long-term safety and outcomes in hereditary tyrosinaemia type 1 with nitisinone treatment: a 15-year non-interventional, multicentre study

Since the EU approval of nitisinone in 2005, prognosis for patients with hereditary tyrosinaemia type 1 has changed dramatically, with patients living with the disease now reaching adulthood for the first time in history. This study aimed to assess the long-term safety and outcomes of nitisinone treatment in patients with hereditary tyrosinaemia type 1. We did a non-interventional, non-comparative, multicentre study in 77 sites across 17 countries in Europe and collected retrospective and prospective longitudinal data in patients with hereditary tyrosinaemia type 1 who were treated with oral nitisinone during the study period (Feb 21, 2005, to Sept 30, 2019). There were no specific exclusion criteria. Patients were followed-up with an investigator at least annually for as long as they were treated, or until the end of the study. The primary endpoints, occurrence of adverse events related to hepatic, renal, ophthalmic, haematological, or cognitive or developmental function, were assessed in the complete set (all patients already receiving treatment at the index date [Feb 21, 2005] or starting treatment thereafter) and the index set (the subset of patients who had their first dose on the index date or later only). 315 patients were enrolled during the study period (complete set). Additionally, data from 24 patients who had liver transplantation or died during the post-marketing surveillance programme were retrieved (extended analysis set; 339 patients). Median treatment duration was 11·2 years (range 0·7-28·4); cumulative nitisinone exposure was 3172·7 patient-years. Patients who were diagnosed by neonatal screening started nitisinone treatment at median age 0·8 months versus 8·5 months in those who presented clinically. Incidences of hepatic, renal, ophthalmic, haematological, or cognitive or developmental adverse events were low. Occurrence of liver transplantation or death was more frequent the later that treatment was initiated (none of 70 patients who started treatment at age <28 days vs 35 [13%] of 268 patients who started treatment at age ≥28 days). 279 (89%) of 315 patients were assessed as having either very good or good nitisinone treatment compliance. Treatment and diet compliance declined as patients aged. Suboptimal plasma phenylalanine and tyrosine levels were observed. The majority of patients were reported to have good overall clinical condition throughout treatment; 176 (87%) of 203 during the entire study, 98% following 1 year of treatment. Long-term nitisinone treatment was well tolerated and no new safety signals were revealed. Life-limiting hepatic disease appears to have been prevented by early treatment start. Neonatal screening was the most effective way of ensuring early treatment. Standardised monitoring of blood tyrosine, phenylalanine, and nitisinone levels has potential to guide individualised therapy. Swedish Orphan Biovitrum (Sobi).

Blueprint for a Simulation Framework to Increase Driver Training Safety in North America: Case Study

Despite numerous recent advances in the classroom and in-vehicle driver training and education over the last quarter-century, traffic accidents remain a leading cause of mortality for young adults—particularly, those between the ages of 16 and 19. Obviously, despite recent advances in conventional driver training (e.g., classroom, in-vehicle, Graduated Driver Licensing programs), this remains a critical public safety and public health concern. As advanced vehicle technologies continue to evolve, so too does the unintended potential for mechanical, visual, and/or cognitive driver distraction and adverse safety events on national highways. For these reasons, a physics-based modeling and high-fidelity simulation have great potential to serve as a critical supplementary component of a near-future teen-driver training framework. Here, a case study is presented that examines the specification, development, and deployment of a “blueprint” for a simulation framework intended to increase driver training safety in North America. A multi-measure assessment of simulated driver performance was developed and instituted, including quantitative (e.g., simulator-measured), qualitative (e.g., evaluator-observed), and self-report metrics. Preliminary findings are presented, along with a summary of novel contributions through the deployment of the training framework, as well as planned improvements and suggestions for future directions.

Epilepsy and Cognitive Impairment

Cognitive impairment is prevalent in epilepsy. Studies have revealed that up to 70%–80% of epilepsy patients have various degrees of cognitive impairment in attention, executive function, language function, and memory. Factors associated with cognitive impairment include, but are not limited to, genetic predisposition; medications (including antiepileptic drugs); structural lesions; degenerative processes; mood disorders; type, frequency and severity of seizures; age of onset; and duration of epilepsy. Antiepileptic drugs, including barbiturates and topiramate, are known to affect cognitive function. However, cognitive impairment is frequently noticed at the onset of epilepsy and antiepileptic drugs usually are not independently associated with cognitive dysfunction. In addition, caution is needed that other factors associated with cognitive impairment does not necessarily entail a causal association. The existence of a common pathomechanism underlying both cognitive impairment and epilepsy should be considered. Vascular insult and tau pathology may underlie both cognitive impairment and epilepsy. Surgery could be a good treatment option for refractory epilepsy. Potential cognitive adverse events following the surgical removal of brain tissue are limited and could be outweighed by succesful seizure control and improved quality of life. Key words: Epilepsy; Cognitive impairment; Elderly; Antiepileptic drug; Epilepsy surgery.

External carotid artery stenting in patients with ipsilateral internal carotid artery occlusion: Peri-operative and 12-month follow-up.

This study aimed to evaluate the safety and clinical efficacy of external carotid artery (ECA) stenting in patients with ipsilateral internal carotid artery (ICA) occlusion. In patients with ICA occlusion, severe ipsilateral ECA stenosis may exacerbate pre-existing cerebral ischemia and cognitive impairment. It remains unclear whether ECA stenting to normalize ECA collaterals to the cerebralis alleviates cerebral ischemia and improves cognitive function. From January 2008 to June 2019, we retrospectively collected clinical data of 36 consecutive patients with ipsilateral ICA occlusion who had undergone ECA stenting (mean age, 66.7 ± 8.3 years; males, n = 26 [72.2%]). Neurocognitive test results, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA) tests, symptom assessment, and adverse events were recorded. ECA stenting was successful in all 36 patients. Intra-operatively, six (16.7%) patients experienced hemodynamic depression during balloon dilation and recovered completely within 2 days. Within a 12-month follow-up period, two patients experienced a transient ischemic attack, one patient had a contralateral minor stroke, and 33 patients remained asymptomatic. No other adverse events occurred in the peri-operative or follow-up periods. Compared with baseline, significant MMSE (25.3 ± 1.3 vs. 23.6 ± 1.7; p < .05) and MOCA (24.1 ± 1.3 vs. 22.8 ± 1.7; p < .05) test score improvements were observed 3 months post-operatively and were maintained throughout follow-up. ECA stenting may improve cerebral ischemia and cognitive function in patients with severe ECA stenosis and ipsilateral ICA occlusion; however, further research is required to support our findings.

Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy.

BackgroundMost gastrointestinal stromal tumors (GIST) driven by KIT or platelet‐derived growth factor receptor A (PDGFRA) mutations develop resistance to available tyrosine kinase inhibitor (TKI) treatments. NAVIGATOR is a two‐part, single‐arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST.Materials and MethodsEligible patients were 18 years or older with histologically or cytologically confirmed unresectable GIST and Eastern Cooperative Oncology Group performance status ≤2 and initiated avapritinib at 300 mg or 400 mg once daily. Primary endpoints were safety in patients who initiated avapritinib at 300 mg or 400 mg once daily and overall response rate (ORR) in patients in the safety population with three or more previous lines of TKI therapy.ResultsAs of November 16, 2018, in the safety population (n = 204), the most common adverse events (AEs) were nausea (131 [64%]), fatigue (113 [55%]), anemia (102 [50%]), cognitive effects (84 [41%]), and periorbital edema (83 [41%]); 17 (8%) patients discontinued due to treatment‐related AEs, most frequently confusion, encephalopathy, and fatigue. ORR in response‐evaluable patients with GIST harboring KIT or non‐D842V PDGFRA mutations and with at least three prior therapies (n = 103) was 17% (95% confidence interval [CI], 10–25). Median duration of response was 10.2 months (95% CI, 7.2–10.2), and median progression‐free survival was 3.7 months (95% CI, 2.8–4.6).ConclusionAvapritinib has manageable toxicity with meaningful clinical activity as fourth‐line or later treatment in some patients with GIST with KIT or PDGFRA mutations.Implications for PracticeIn the NAVIGATOR trial, avapritinib, an inhibitor of KIT and platelet‐derived growth factor receptor A tyrosine kinases, provided durable responses in a proportion of patients with advanced gastrointestinal stromal tumors (GIST) who had received three or more prior therapies. Avapritinib had a tolerable safety profile, with cognitive adverse events manageable with dose interruptions and modification in most cases. These findings indicate that avapritinib can elicit durable treatment responses in some patients with heavily pretreated GIST, for whom limited treatment options exist.

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke.

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke.

Household interventions for secondary prevention of domestic lead exposure in children.

Household interventions for secondary prevention of domestic lead exposure in children.

Anticholinergics May Carry Significant Cognitive and Gait Burden in Parkinson's Disease

Anticholinergic drugs are associated with significant cognitive and other adverse events in older adults, including those with Parkinson's disease (PD). Anticholinergic effects are considered lesser in younger individuals and the burden and outcomes in younger patients with PD are unknown. To determine the cumulative anticholinergic burden in a cohort of younger of patients with PD and to correlate the same with cognitive impairment and freezing of gait (FOG). We conducted a cross-sectional study to identify the cumulative anticholinergic burden from medications prescribed to patients with PD. Two standard scales, the Anticholinergic Cognitive Burden (ACB) scale and the ACB score, were used to calculate the anticholinergic burden from prescriptions. We identified commonly prescribed drugs contributing to anticholinergic effects and correlated the cumulative ACB score with cognitive impairment (Movement Disorder Society-Unified Parkinson's Disease Rating Scale item 1.1) and FOG (Movement Disorder Society-Unified Parkinson's Disease Rating Scale items 2.13 and 3.11). We recruited 287 patients with PD (68.9% male) with a mean age of 56.9 ± 11.8 years and a duration of symptoms 6.3 ± 6.9 years. Median ACB score was 4 (range 0-12). A total of 164 (58.4%) patients had total ACB score > 3. ACB score > 3 was independently associated with cognitive impairment (Odds Ratio, 2.55; 95% confidence interval, 1.43-4.53; P < 0.001) and FOG using patient-reported measures (Odds Ratio, 3.192; 95% Confidence Interval, 1.68-6.07; P < 0.001) and objective measures (odds ratio, 2.41; 95% confidence interval, 1.27-4.6, P = 0.007). Patients with PD are exposed to significant anticholinergic burden from drugs prescribed for PD and non-PD indications. Higher anticholinergic burden is associated with cognitive impairment and FOG even in younger patients with PD.

Androgen deprivation therapy and side effects: are GnRH antagonists safer?

Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.

Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis

Drug-induced Mood- and Cognition-related adverse events (MCAEs) are often only detected during the clinical trial phases of drug development, or even after marketing, thus posing a major safety concern and a challenge for both pharmaceutical companies and clinicians. To fill some gaps in the understanding and elucidate potential biological mechanisms of action frequently associated with MCAEs, we present a unique workflow linking observational population data with the available knowledge at molecular, cellular, and psychopharmacology levels. It is based on statistical analysis of pharmacovigilance reports and subsequent signaling pathway analyses, followed by evidence-based expert manual curation of the outcomes. Our analysis: (a) ranked pharmaceuticals with high occurrence of such adverse events (AEs), based on disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database, and (b) identified 120 associated genes and common pathway nodes possibly underlying MCAEs. Nearly two-thirds of the identified genes were related to immune modulation, which supports the critical involvement of immune cells and their responses in the regulation of the central nervous system function. This finding also means that pharmaceuticals with a negligible central nervous system exposure may induce MCAEs through dysregulation of the peripheral immune system. Knowledge gained through this workflow unravels putative hallmark biological targets and mediators of drug-induced mood and cognitive disorders that need to be further assessed and validated in experimental models. Thereafter, they can be used to substantially improve in silico/in vitro/in vivo tools for predicting these adversities at a preclinical stage.

Efficacy and Safety of Deep Transcranial Magnetic Stimulation in Office Workers with Treatment-Resistant Depression: A Randomized, Double-Blind, Sham-Controlled Trial

Objectives: Major depression is a highly prevalent disorder that causes economic burden in office workers. We conducted a randomized, double-blind, sham-controlled trial to evaluate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) in office workers with treatment-resistant depression. Methods: In this study, we randomized office workers taking administrative leave for treatment-resistant major depressive disorder or bipolar disorder with current major depressive episode. dTMS treatment was applied at 120% resting motor threshold with 18 Hz over the left dorsolateral prefrontal cortex. The treatment sessions delivered a total of 1,980 pulses a day, 5 days a week, for 4–6 weeks. The primary outcome was change in the total score on the 21-item Hamilton Depression Rating Scale (HDRS-21) from baseline to the end of study in an intent-to-treat analysis. The secondary outcomes were the response and remission rates. We also assessed changes in cognitive function and adverse events. Results: Forty patients were randomized to active or sham dTMS groups (1:1). The change in the total score on the HDRS-21 was more significantly improved in the active group than in the sham group at 6 weeks (p = 0.045). There were no significant differences in the response and remission rates or cognitive measures between the active and sham groups. No serious adverse events were observed in either group. Conclusions: These results suggest that dTMS might be effective and safe in office workers with treatment-resistant depression. Further well-designed studies are needed.

Effects of Methylphenidate on Cognitive Function in Adults with Traumatic Brain Injury: A Meta-Analysis.

This meta-analysis evaluated the effects of methylphenidate (MPH) on cognitive outcome and adverse events in adults with traumatic brain injuries (TBI). We searched PubMed, EMBASE, and PsycINFO for randomized controlled trials (RCTs) published before July 2019. Studies that compared the effects of MPH and placebos in adults with TBI were included. The primary outcome was cognitive function, while the secondary outcome was adverse events. Meta-regression and sensitivity analysis were conducted to evaluate heterogeneity. Seventeen RCTs were included for qualitative analysis, and ten RCTs were included for quantitative analysis. MPH significantly improved processing speed, measured by Choice Reaction Time (standardized mean difference (SMD): −0.806; 95% confidence interval (CI): −429 to −0.182, p = 0.011) and Digit Symbol Coding Test (SMD: −0.653; 95% CI: −1.016 to −0.289, p < 0.001). Meta-regression showed that the reaction time was inversely associated with the duration of MPH. MPH administration significantly increased heart rate (SMD: 0.553; 95% CI: 0.337 to 0.769, p < 0.001), while systolic or diastolic blood pressure did not exhibit significant differences. Therefore, MPH elicited better processing speed in adults with TBI. However, MPH use could significantly increase heart rate. A larger study is required to evaluate the effect of dosage, age, or optimal timing on treatment of adults with TBI.

Less memory complaints with reduced stimulus dose during electroconvulsive therapy for depression

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for depression, but there is risk of cognitive adverse events. This risk has been partially attributed to electrical charge, thus the optimal electrical stimulus dose is still under discussion. The aim of this study was to evaluate how the risk of subjective memory worsening was changed after lowering stimulus dose during ECT for patients with major depression. MethodA retrospective register-based intervention study of the effects of reduced electrical charges for patients receiving ECT for depression was conducted. The primary outcome was subjective memory worsening and the secondary outcome change in effect on depressive symptoms. ResultsA total of 154 patients were enrolled in the study (High dosage group: n = 57; Lower dosage group: n = 97). Subjective memory worsening after ECT occurred in 44% of patients in the high dosage group and in 25% of patients in the lower dosage group(p = 0.014). There was no significant between-group difference in the anti-depressive effect of ECT. LimitationsThe study was register-based and the two groups were not randomized. A large portion of patients were initially excluded due to missing data in the register. The study lacks a long-term follow up. ConclusionAfter implementing a change of treatment protocol, that lowered ECT stimulus doses from high to moderate, the occurrence of subjective memory worsening was significantly reduced without compromising treatment results.

Cognitive impairment, adverse events and mortality among elderly patients treated with long-term oral anticoagulation: A monocentric prospective study

Oral anticoagulants (AC) represent the leading cause of iatrogenic morbimortality in France. AC are widely prescribed among the elderly. The assessment of the cognitive impairment (CI) is not included within the common thrombotic and bleeding risk scores. The objective of this study was to examine an association between CI and adverse events in patients receiving long term oral AC. A prospective monocentric cohort study was conducted in patients (> 60 years-old) on oral AC. Death, hemorrhages, falls, hospital readmission and thromboembolic events were collected over 6 months follow-up. Patients were included during an hospitalization for any medical or surgical condition and divided into three groups, according to their Mini Mental State Examination (MMSE): Group 1 (absence of CI) MMSE > 26, Group 2 (mild CI) 23 < MMSE < 27, Group 3 (significant CI) MMSE < 24. Regardless of the kind of oral AC, among 120 patients (mean age: 82,2 ± 8,8 years), the all-causes mortality ( n = 25) was significantly higher in the Group 3 ( n = 17, P = 0,006); this also applies to the incidence of falls ( n = 34, P = 0,009) or major hemorrhages ( n = 10, P = 0,023). There was no thromboembolic event. Minor hemorrhages and hospital readmissions were not different in the 3 groups. After 6 months of follow up, the cognitive impairment was associated with mortality, major hemorrhages and falls among the elderly receiving oral AC. A systematic assessment of cognitive functions of these patients seems to be essential to analyze the global risk and the risks related to the AC treatment.

Behavioral, Psychiatric, and Cognitive Adverse Events in Older Persons Treated with Glucocorticoids.

Background: Since the introduction of glucocorticoids (GCs) in the physician’s pharmacological arsenal, it has been known that they are a cause of behavioral or psychiatric adverse events (BPAE), as well as of cognitive problems. To the best of our knowledge, the relationship between these adverse events and GCs in older persons has never been evaluated, except through case-reports or series with few cases. In this paper, a review of the literature regarding BPAEs and cognitive disorders in older people treated with CSs is undertaken. Methods: A comprehensive literature search for BPAEs was carried out on the three main bibliographic databases: EMBASE, MEDLINE and PsycINFO (NICE HDAS interface). Emtree terms were: Steroid, steroid therapy, mental disease, mania, delirium, agitation, depression, behavior change, dementia, major cognitive impairment, elderly. The search was restricted to all clinical studies and case reports with focus on the aged (65+ years) published in any language since 1998. Results: Data on the prevalence of the various BPAEs in older patients treated with GCs were very scarse, consisting mainly of case reports and of series with small numbers of patients. It was hence not possible to perform any statistical evaluation of the data (including meta-analysis). Amongst BPAEs, he possibility that delirium can be induced by GCs has been recently been questioned. Co-morbidities and polypharmacy were additional risk factors for BPAEs in older persons. Conclusions: Data on BPAEs in older persons treated with GCs, have several unmet needs that need to be further evaluated with appropriately designed studies.

Analysis of Cognitive Adverse Events in Two Phase III Conversion-to-Eslicarbazepine Acetate (ESL) Monotherapy Trials (P5.277)

Analysis of Cognitive Adverse Events in Two Phase III Conversion-to-Eslicarbazepine Acetate (ESL) Monotherapy Trials (P5.277)

Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures

ObjectiveTo evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. MethodsThis was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400mg (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. ResultsThe analysis population included 1447 patients (ESL, n=1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p=0.802). However, the incidence of depression and suicidality-related TEAEs was significantly higher for ESL (7.4%) vs. placebo (3.8%) (p=0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was significantly higher for ESL (7.1%) vs. placebo (4.0%) (p=0.023); incidences of memory impairment, attention disturbance, apathy, aphasia, and bradyphrenia were higher for ESL 1200mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs (SAEs) were 0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL, and 0.7% and 0.5% taking placebo, respectively. ConclusionsIn phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. However, the incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were significantly higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo.

Effects of dance on cognitive function among older adults: a protocol for systematic review and meta-analysis

BackgroundCognitive impairment is characterized by problems in thinking, memory, language, and judgment that are greater than cognitive changes in normal aging. Considering the unprecedented growth of the older adult population and the projected increase in the prevalence of cognitive impairment, it is imperative to find effective strategies to improve or maintain cognitive function in older adults. The objective of this review is to summarize the effects of dance versus any other control group on cognitive function, physical function, adverse events, and quality of life in older adults.MethodWe will search the following databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify the randomized controlled trials (RCTs) evaluating the effects of dance on cognitive function among older adults. Also, we will search http://apps.who.int/trialsearch, clinicaltrials.gov and conference abstracts to identify ongoing and unpublished studies. There will be no restrictions on language, date, or journal of publication. Reviewers will independently and in duplicate screen for eligible studies using pre-defined criteria. Data extraction from eligible studies will be performed independently and in duplicate. The Cochrane risk of bias tool will be used to assess the risk of bias of studies. Our primary outcome of interest is cognitive function, more specifically the executive function domain. We will include other domains as well such as processing speed and reaction time. Secondary outcomes of interest are physical function. The secondary outcomes also include adverse events including falls and quality of life. We will use Review Manager (RevMan 5.3) to pool the effect of dance for each outcome where possible. Results will be presented as relative risks along with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. We will assess the certainty of the evidence using the GRADE approach and present findings in a Summary of Findings table.DiscussionThis systematic review, to our best knowledge the first-ever, will synthesize the available evidence on the effects of dance on cognitive function among older people.Systematic review registrationPROSPERO CRD42017057138

Household interventions for preventing domestic lead exposure in children.

Household interventions for preventing domestic lead exposure in children.