Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

OBJECTIVE: Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. METHODS: Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. RESULTS: Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d' and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month). SIGNIFICANCE: Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double-blind, placebo-controlled clinical trials are needed.

Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure.

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.

Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Depressive and anxiety disorders in epilepsy: do they differ in their potential to worsen common antiepileptic drug-related adverse events?

PURPOSE: To compare the effect of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on antiepileptic drug (AED)-related adverse events (AEs) in persons with epilepsy (PWE). METHODS: The study included 188 consecutive PWE from five U.S. outpatient epilepsy clinics, all of whom underwent structured interviews (SCID) to identify current and past mood disorders and other current Axis I psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. A diagnosis of SSDE was made in patients with total Beck Depression Inventory-II (BDI-II) scores >12 or the Centers of Epidemiologic Studies-Depression (CES-D) > 16 (in the absence of any DSM diagnosis of mood disorder. The presence and severity of AEs was measured with the Adverse Event Profile (AEP). KEY FINDINGS: Compared to asymptomatic patients (n = 103), the AEP scores of patients with SSDE (n = 26), MDE only (n = 10), anxiety disorders only (n = 21), or mixed MDE/anxiety disorders (n = 28) were significantly higher, suggesting more severe AED-related AEs. Univariate analyses revealed that having persistent seizures in the last 6 months and taking antidepressants was associated with more severe AEs. Post hoc analyses, however, showed that these differences were accounted for by the presence of a depressive and/or anxiety disorders. SIGNIFICANCE: Depressive and anxiety disorders worsen AED-related AEs even when presenting as a subsyndromic type. These data suggest that the presence of psychiatric comorbidities must be considered in their interpretation, both in clinical practice and AED drug trials.

Depression and epilepsy, pain and psychogenic non-epileptic seizures: clinical and therapeutic perspectives.

The clinical manifestations of depression in people with epilepsy (PWE) are pleomorphic, often associated with anxiety symptoms and anxiety disorders. The ongoing debate of whether the clinical presentation of depression in PWE is unique to this neurologic disorder is reviewed. Comorbid depression can impact the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs). Yet, the impact of depression on the response of the seizure disorder to pharmacotherapy with AEDs and its impact on worse adverse events may bias the interpretation of the trial findings, particularly when depressed patients are included in the AED trials. PWE have a greater suicidal risk than the general population. This risk is mediated by multiple factors, and recent data from the FDA have imputed a potential pathogenic role to all AEDs. The recognition of patients at risk is reviewed. Yet, the validity of the FDA data has been questioned, and the status of this controversial question is analyzed. As in the case of epilepsy, depression and pain syndromes have a relatively high comorbidity. The negative impact of depression on pain is reminiscent of that of depression in PWE; furthermore, the high comorbidity may be also associated with the existence of common pathogenic mechanisms. Neurologists and in particular, epileptologists establish the diagnosis of psychogenic non-epileptic seizures (PNES) in whom a comorbid depressive disorder is very often identified. The role of depression in the course of PNES and its treatment are discussed. Scarce data are available on the treatment of depression in PWE. Thus, clinicians have had to adopt data from patients with primary depressive disorders. We outline a consensus strategy on the identification and treatment of depressive disorders in adult and pediatric patients with epilepsy.

Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence.

Depression is the most frequent psychiatric comorbidity in people with epilepsy (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial variables play a pathogenic role in the high comorbid occurrence of these two disorders. These variables were critically examined during an international symposium held in Chicago in September 2010, the results of which are presented in two companion manuscripts. The first manuscript summarizes new epidemiologic data highlighting the bidirectional relation between depression and epilepsy and related methodological issues in studying this relationship. An examination of the neurobiologic aspects of primary mood disorders, mood disorders in PWE and pathogenic mechanisms of epilepsy derived from studies in animal models and humans is allowing a better understanding of the complex relation between the two conditions. In the first manuscript, we review data from animal models of epilepsy in which equivalent symptoms of depression and anxiety disorders develop and, conversely, animal models of depression in which the kindling process is facilitated. Data from structural and functional neuroimaging studies in humans provide a further understanding of potential common pathogenic mechanisms operant in depression and epilepsy that may explain their high comorbidity. The negative impact of depression on the control of seizure disorders has been documented in various studies. In this manuscript, these data are reviewed and potential mechanisms explaining this phenomenon are proposed.

Suicidality and epilepsy: a neuropsychobiological perspective.

People with epilepsy (PWE) are at increased risk of experiencing suicidal ideation, displaying suicidal behavior, and committing suicide than the general population. The relationship between suicidality and epilepsy is complex and multifactorial in which operant pathogenic mechanisms include epilepsy-related variables, personal and familial psychiatric history, and iatrogenic effects. Furthermore, a bidirectional relationship between suicidality and epilepsy has suggested the existence of common neurobiological pathogenic mechanisms operant in both conditions and including disturbances of several neurotransmitters, in particular, serotonin (5HT), norepinephrine (NE), glutamate (GTE), and γ-aminobutyric acid (GABA), and disturbances of the hypothalamic-pituitary-adrenal axis (HPAA), which, in turn, can result in abnormal secretion of some of these neurotransmitters. The purpose of this article is to review these common neurobiological pathogenic mechanisms.

Anxiety disorders, subsyndromic depressive episodes, and major depressive episodes: do they differ on their impact on the quality of life of patients with epilepsy?

AIMS OF THE STUDY: To compare the impact of anxiety disorders, major depressive episodes (MDEs), and subsyndromic depressive episodes (SSDEs) on the quality of life of patients with epilepsy (PWEs), and to identify the variables predictive of poor quality of life. METHODS: A psychiatric diagnosis according to DSM-IV-TR criteria was established in 188 consecutive PWEs with the MINI International Neuropsychiatric Interview. Patients also completed the Beck Depression Inventory-II (BDI-II), the Centers for Epidemiologic Studies-Depression (CES-D), and the Quality of Life in Epilepsy-89 (QOLIE-89). A diagnosis of SSDE was made in any patient with total scores of the BDI-II >12 or CES-D >16 in the absence of any DSM-IV diagnosis of mood disorder according to the MINI. RESULTS: Patients with SSDEs (n = 26) had a worse quality of life than asymptomatic patients (n = 103). This finding was also observed among patients with MDEs only (n = 10), anxiety disorders only (n = 21), or mixed MDEs/anxiety disorders (n = 28). Furthermore, having mixed SSDEs/anxiety disorders yielded a worse quality of life than having only SSDEs. Independent predictors of poor quality of life included having a psychiatric disorder and persistent epileptic seizures in the last 6 months. CONCLUSIONS: Although isolated mood and anxiety disorders, including SSDE, have a comparable negative impact on the quality of life of PWEs; the comorbid occurrence of mood and anxiety disorders yields a worse impact. In addition, seizure freedom in the previous 6 months predicts a better quality of life.

Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.

BACKGROUND: Data from the fields of genetics, neuroimaging, and animal studies, along with case reports and small clinical trials, point to a role for glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). We report on the first open-label study to test the hypothesis that memantine, a noncompetitive glutamate antagonist, will result in a clinically meaningful reduction in OCD symptoms in adults with treatment-resistant OCD. METHODS: We recruited 15 adult subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18 or higher, who had failed to respond to treatment with a serotonin reuptake inhibitor (SRI), given at an adequate and stable dose for at least 12 weeks. The duration of memantine treatment was 12 weeks, and the dose was gradually increased to a target of 20 mg/d. Response was defined as a 25% or greater reduction in the Y-BOCS score at study end and a Clinical Global Impression-Improvement scale rating of "much" or "very much" improved. RESULTS: Data from 14 subjects were analyzable. Mean baseline Y-BOCS score was 27.4 (SD, 5.0). Subjects had failed an average of 2.8 (SD, 1.8) SRI trials; 6 subjects had failed augmentation with atypical antipsychotics. At study end, 6 subjects (42.9%) were responders, and response was achieved by EOW4. Responders had significantly lower baseline Y-BOCS scores (2-tailed t tests, P < 0.05, t = 2.2) and had failed fewer SRIs (P

Hemostatic Comparison of a Polysaccharide Powder and a Gelatin Powder.

Purpose/Aim: Powdered hemostats have been widely adopted for their ease-of-use; however, their efficacy has been limited resulting in applications restricted to low-level bleeds. This study investigates the use of bovine-derived gelatin particles (BGP) as a standalone hemostatic powder and compare BGP to commercially available microporous polysaccharide hemospheres (MPH). Materials and Methods: The powders were investigated for their hemostatic efficacy in a heparinized pre-clinical bleeding model limited to grade 1 and 2 bleeds on a validated intraoperative bleeding scale, which represents the accepted, clinical use of hemostatic powders. Results: At 10 minutes, the hemostatic success of lesions treated with BGP were 78% while MPH were 22%. The odds ratio for hemostatic success of BGP relative to MPH was 15.18 (95% CI: 7.37, 31.27). The 95% lower limit of the odds ratio was greater than 1. This indicates that BGP are superior to MPH (p < 0.001). The median time to hemostasis for BGP was 1.6 minutes and MPH was 14.5 minutes. The ratio for time to hemostasis of MPH relative to BGP was 9.23 (95% CI: 6.99, 12.19). This indicates that BGP achieve significantly faster time to hemostasis (p < 0.001). Conclusions: Characterization of tissue explant ultrastructure, particle size, and swelling revealed differences in the materials. BGP, in addition to absorbing fluid and concentrating clotting factors and platelets, integrate into the clot and stabilize the fibrin matrix. BGP have advantages over MPH in terms of speed and efficacy. BGP are a favorable biomaterial for further research that greatly improve the limited efficacy of powdered hemostats.

The effect of mesenchymal populations and vascular endothelial growth factor delivered from biodegradable polymer scaffolds on bone formation.

The capacity to deliver, temporally, bioactive growth factors in combination with appropriate progenitor and stem cells to sites of tissue regeneration promoting angiogenesis and osteogenesis offers therapeutic opportunities in regenerative medicine. We have examined the bone regenerative potential of encapsulated vascular endothelial growth factor (VEGF(165)) biodegradable poly(DL-lactic acid) (PLA) scaffolds created using supercritical CO(2) fluid technology to encapsulate and release solvent-sensitive and thermolabile growth factors in combination with human bone marrow stromal cells (HBMSC) implanted in a mouse femur segmental defect (5 mm) for 4 weeks. HBMSC seeded on VEGF encapsulated PLA scaffolds showed significant bone regeneration in the femur segmental defect compared to the scaffold alone and scaffold seeded with HBMSC as analysed by indices of increased bone volume (BV mm(3)), trabecular number (Tb.N/mm) and reduced trabecular separation (Tb.Sp.mm) in the defect region using micro-computed tomography. Histological examination confirmed significant new bone matrix in the HBMSC seeded VEGF encapsulated scaffold group as evidenced by Sirius red/alcian blue and Goldner's trichrome staining and type I collagen immunocytochemistry expression in comparison to the other groups. These studies demonstrate the ability to deliver, temporally, a combination of VEGF released from scaffolds with seeded HBMSC to sites of bone defects, results in enhanced regeneration of a bone defect.

Controlling protein release from scaffolds using polymer blends and composites.

We report the development of three protein loaded polymer blend and composite materials that modify the release kinetics of the protein from poly(dl-lactic acid) (P(dl)LA) scaffolds. P(dl)LA has been combined with either poly(ethylene glycol) (PEG), poly(caprolactone) (PCL) microparticles or calcium alginate fibres using supercritical CO(2) (scCO(2)) processing to form single and dual protein release scaffolds. P(dl)LA was blended with the hydrophilic polymer PEG using scCO(2) to increase the water uptake of the resultant scaffold and modify the release kinetics of an encapsulated protein. This was demonstrated by the more rapid release of the protein when compared to the release rate from P(dl)LA only scaffolds. For the P(dl)LA/alginate scaffolds, the protein loaded alginate fibres were processed into porous protein loaded P(dl)LA scaffolds using scCO(2) to produce dual release kinetics from the scaffolds. Protein release from the hydrophilic alginate fibres was more rapid in the initial stages, complementing the slower release from the slower degrading P(dl)LA scaffolds. In contrast, when protein loaded PCL particles were loaded into P(dl)LA scaffolds, the rate of protein release was retarded from the slow degrading PCL phase.

Consensus statement: the evaluation and treatment of people with epilepsy and affective disorders.

Affective disorders in people with epilepsy (PWE) have become increasingly recognized as a primary factor in the morbidity and mortality of epilepsy. To improve the recognition and treatment of affective disorders in PWE, an expert panel comprising members from the Epilepsy Foundation's Mood Disorders Initiative have composed a Consensus Statement. This document focuses on depressive disorders in particular and reviews the appearance and treatment of the disorder in children, adolescents, and adults. Idiosyncratic aspects of the appearance of depression in this population, along with physiological and cognitive issues and barriers to treatment, are reviewed. Finally, a suggested approach to the diagnosis of affective disorders in PWE is presented in detail. This includes the use of psychometric tools for diagnosis and a stepwise algorithmic approach to treatment. Recommendations are based on the general depression literature as well as epilepsy-specific studies. It is hoped that this document will improve the overall detection and subsequent treatment of affective illnesses in PWE.

Lamotrigine in patients with epilepsy and comorbid depressive symptoms.

PURPOSE: This open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy. METHODS: Eligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states. Evaluations were conducted at baseline, at the end of 19 weeks of adjunctive treatment, and 36 weeks following conversion to monotherapy. RESULTS: One hundred and fifty-eight patients with epilepsy participated; 96 patients completed adjunctive treatment, and 66 patients completed monotherapy. Intent-to-treat analyses for all instruments showed improvement in depression scores after adjunctive LTG treatment. Improvement was maintained for those converted to monotherapy. CONCLUSIONS: These data suggest that LTG may have antidepressant activity for patients with epilepsy and comorbid low to moderate depressive symptoms, and warrant a randomized controlled trial for validation.

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

OBJECTIVE: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. METHODS: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. RESULTS: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. CONCLUSIONS: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. CLINICALTRIALSGOV IDENTIFIER: NCT02178995. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints.

Rapid detection of major depression in epilepsy: a multicentre study.

BACKGROUND: Depression is a common comorbid disorder in epilepsy but is not routinely assessed in neurology clinics. We aimed to create a rapid yet accurate screening instrument for major depression in people with epilepsy. METHODS: We developed a set of 46 items to identify symptoms of depression that do not overlap with common comorbid cognitive deficits or adverse effects of antiepileptic drugs. This preliminary instrument and several reliable and valid instruments for diagnosis of depression on the basis of criteria from the Diagnostic and Statistical Manual IV, depression symptom severity, health status, and toxic effects of medication were applied to 205 adult outpatients with epilepsy. We used discriminant function analysis to identify the most efficient set of items for classification of major depression, which we termed the neurological disorders depression inventory for epilepsy (NDDI-E). Baseline data for 229 demographically similar patients enrolled in two other clinical studies were used for verification of the original observations. FINDINGS: The discriminant function model for the NDDI-E included six items. Internal consistency reliability of the NDDI-E was 0.85 and test-retest reliability was 0.78. An NDDI-E score of more than 15 had a specificity of 90%, sensitivity of 81%, and positive predictive value of 0.62 for a diagnosis of major depression. Logistic regression showed that the model of association of major depression and the NDDI-E was not affected by adverse effects of antiepileptic medication, whereas models for depression and generic screening instruments were. The severity of depression symptoms and toxic effects of drugs independently correlated with subjective health status, explaining 72% of variance. Results from a separate verification sample also showed optimum sensitivity, specificity, and predictive power at a cut score of more than 15. INTERPRETATION: Major depression in people with epilepsy can be identified by a brief set of symptoms that can be differentiated from common adverse effects of antiepileptic drugs. The NDDI-E could enable rapid detection and improve management of depression in epilepsy in accordance with internationally recognised guidelines.

Incorporation of proteins within alginate fibre-based scaffolds using a post-fabrication entrapment method.

In this study, a physical entrapment process was explored for the incorporation of proteins within preformed fibrous alginates and the release profile was tuned by varying the processing parameters. The entrapment process was carried out in a series of aqueous solutions at room temperature and involved pre-swelling of the fibrous alginate within a Na(+)-rich solution, followed by exposure to the protein of choice and entrapping it by re-establishing cross-links of alginate with BaCl2. Entrapment and release of fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA), a model protein, was studied. It was found that a sustained release of the incorporated protein in cell culture medium for about 6 days was achieved. The main factors determining the release profile included the NaCl/CaCl2 ratio in the pre-swelling solution, protein concentration, and the exposure time. To retard protein release, alginate fibres with entrapped FITC-BSA were processed together with poly(D, L-lactide) (PDLLA) into porous alginate fibre/PDLLA composites using supercritical CO2. In this manner, release of the protein for up to 3 months was achieved.

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.