Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats

IntroductionMultiple lines of investigation have explored the role of glutamatergic and purinergic systems in epilepsy, related cognitive impairment, and oxidative stress. Glutamate transporters, particularly GLT-1 expression, were found to be decreased, and purinergic receptor, P_2X7 expression, was found to be increased in brain tissue associated with epilepsy. The present study was carried out to investigate the effect of ceftriaxone (GLT-1 upregulator) and Brilliant Blue G (P_2X7 antagonist) against PTZ-induced kindling in rats. The study was further extended to elucidate the cross-link between glutamatergic and purinergic pathways in epilepsy.Material and methodsSystemic administration of subconvulsant dose of PTZ (30 mg/kg) every other day for 27 days (14 injections) significantly increased the mean kindling, and developed generalized tonic–clonic seizures, and reduced motor co-ordination, cognitive skills, oxidative defense (increases lipid peroxidation, nitrite levels and decreases GSH level) and acetylcholinesterase enzyme activities in the cortex and subcortical region. Treatments with CEF (100 and 200 mg/kg) and BBG (15 and 30 mg/kg) alone and in combination (CEF 100 mg/kg and BBG 15 mg/kg) significantly decreased the mean kindling score and restored behavioral and oxidative defense activities compared with treatment with PTZ.ConclusionsThe combination of both the drugs was shown to have better effect in preventing kindled seizures and a significantly synergistic effect compared with their effect alone in PTZ-kindled rats. The present study elucidated the mechanistic role of GLT-1 modulator and selective P_2X7 antagonist and their combination against PTZ-induced kindling. The study for the first time demonstrated the cross-link between glutamatergic and purinergic pathways in epilepsy treatment.     

Psychoeducation and cognitive-behavioral therapy for patients with refractory bipolar disorder: A 5-year controlled clinical trial

ObjectiveThe aim of this research, which represents an additional and longer follow-up to a previous trial, was to evaluate a 5-year follow-up study of a combined treatment (pharmacological + psychoeducational and cognitive-behavioral therapy) as compared with a standard pharmacological treatment in patients with refractory bipolar disorder.MethodForty patients were randomly assigned to either an Experimental group–under combined treatment — or a Control group — under pharmacological treatment. Data were analyzed by analysis of variance (ANOVA), with repeated measures at different evaluation time points.ResultsBetween-group differences were significant at all evaluation time points after treatment. Experimental group had less hospitalization events than Control group in the 12-month evaluation (P = 0.015). The Experimental group showed lower depression and anxiety in the 6-month (P = 0.006; P = 0.019), 12-month (P = 0.001; P < 0.001) and 5-year (P < 0.001, P < 0.001) evaluation time points. Significant differences emerged in mania and misadjustment already in the post-treatment evaluation (P = 0.009; P < 0.001) and were sustained throughout the study (6-month: P = 0.006, P < 0.001; 12-month: P < 0.001, P < 0.001; 5-year: P = 0.004, P < 0.001). After 5-year follow-up, 88.9% of patients in the Control group and 20% of patients in the Experimental group showed persistent affective symptoms and/or difficulties in social-occupational functioning.ConclusionsA combined therapy is long-term effective for patients with refractory bipolar disorder. Suggestions for future research are commented.     

Angiotensin II infusion in man is proinflammatory but has no short-term effects on thrombin generation in vivo

BackgroundAngiotensin (Ang) II may be involved in the development of cardiovascular disease. We examined the potential proinflammatory and prothrombotic effects of Ang II in 16 healthy subjects and in 16 subjects with familial combined hyperlipidemia (FCHL), a condition associated with an increased risk of cardiovascular complications.MethodsWe studied the effects of a three hour intravenous infusion of Ang II (10 ng/kg/min) on plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), circulating leukocyte count, tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) complexes, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin (TAT) complexes. Blood was collected before, during and 1 h after Ang II infusion.ResultsIL-6 was higher in subjects with FCHL at rest (P < 0.05) and increased (P < 0.001) similarly in both groups by Ang II infusion. Also leukocyte count was higher in subjects with FCHL at rest (P < 0.001) and increased (P < 0.001) similarly in both groups by Ang II infusion. T-PA/PAI-1 complexes were higher in subjects with FCHL at rest (P < 0.001) and decreased (P < 0.001) similarly in both groups during Ang II infusion. TNF-α, F1 + 2 and TAT complexes were similar in the two groups at rest and did not change during or after the Ang II infusion.ConclusionsA three hour Ang II infusion increases inflammation and may enhance fibrinolysis but does not affect short term thrombin generation. Subjects with FCHL have signs of increased inflammation and impaired fibrinolysis.     

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats

BackgroundEpilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of antiepileptic drugs (AEDs) in the past 20 years, the seizures of around 30% of patients with epilepsy remain refractory to available treatment. Also, available AEDs and the disease itself have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine has potential antiepileptic and memory-enhancing properties because of its involvement in the transmethylation reaction.ObjectivesThe present study was designed to evaluate the antiepileptic effect of S-adenosyl methionine and its role in memory impairment in the pentylenetetrazole (PTZ)-induced kindling model in rats.Materials and methodsThe antiepileptic effect of 2 doses of SAM (50 and 100 mg/kg) was tested by evaluating seizure severity score and seizure latency in the pentylenetetrazole-induced kindling model in rats. At the end of the study, spatial memory was evaluated in an elevated plus maze (EPM) test, and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate.ResultsA higher dose of SAM (100 mg/kg) exhibited an increase in seizure latency and a decrease in seizure severity score, suggesting its antiepileptic activity in the PTZ-induced kindling model. Also, the administration of SAM (50 and 100 mg/kg) showed a decrease in transfer latency in the EPM test compared to the disease control group (p < 0.0001). Biochemical analysis of rat brain tissue revealed significantly decreased malondialdehyde (p < 0.0001) and increased glutathione (GSH) (p < 0.0001) in the SAM 100-mg/kg group compared with that in the disease control group.ConclusionThe results demonstrated that S-adenosyl methionine exerts antiepileptic, memory-enhancing, and antioxidant properties in a pentylenetetrazole-induced kindling model of epilepsy.     

Mitigating effect of chrysin loaded solid lipid nanoparticles against Amyloid β25–35 induced oxidative stress in rat hippocampal region: An efficient formulation approach for Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia. Amyloid-β_25–35 (Aβ_25–35), a well-established neurotoxicant, is reported to be involved in the etiology of AD. Chrysin (CN) with its wide range of biological activities in terms of reversing the neuronal damage once induced is limited due to its compromised bioavailability. Solid lipid nanoparticles (SLNs) on the other hand due to its improved protein stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules could be widely applied as a drug delivery vehicle. Hence, in the present investigation, we prepared CN loaded SLNs (CN-SLNs) and investigated its therapeutic role in alleviating Aβ_25–35 administered neuronal damage. All the antioxidant enzymes and non-antioxidant enzyme in hippocampus were reduced significantly (P < 0.01) in the Aβ_25–35 injected group, whereas lipid peroxidation and acetylcholine esterase were increased significantly (P < 0.01). These changes were restored significantly (P < 0.01) by CN-SLNs (5 mg/kg and 10 mg/kg) and (P < 0.05) by free CN (50 mg/kg and 100 mg/kg). Aβ_25–35 also resulted in poor memory retention in behavioral tasks and histopathological sections of the hippocampal region showed the extent of neuronal loss which was thereby restored back on treatment with CN-SLNs and free CN. Our findings demonstrate that the therapeutic efficacy of CN could be attained at lower dose and also its oral bioavailability could be increased by encapsulating CN in SLNs. Thus the results suggest that CN-SLNs could be used as a potential therapeutic and a brain targeting strategy to combat the global burden of Alzheimer's disease.     

ADHD and addictive behavior in crack-cocaine users

BackgroundCrack consumption is a major public health issue in Martinique with a poor prognosis. A preliminary study has found a high prevalence of history of childhood ADHD (C-ADHD) in crack users.ObjectiveTo determine the prevalence of C-ADHD and adult ADHD (A-ADHD) in crack users and their potential associations with substance use behavior.MethodsAll consecutive patients consulting in the public academic hospital covering 376,000 inhabitants were included in the present study and received a comprehensive battery measuring addictive behavior, psychiatric and somatic comorbidities. C-ADHD groups and A-ADHD groups were defined with the Wender-Utah Rating Scale-25 and the Brown ADD Rating Scale, respectively. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS-11).FindingsIn total, 111 participants were evaluated. Among them, 50 (45%) were classified in the C-ADHD group and 20 (18%) in the A-ADHD group. Compared to the patients without ADHD, those with ADHD were found to have higher impulsivity (C-ADHD: BIS total score 67.90 (10.1) vs. 63.28 (10.5), P = 0.021, BIS attentional score 17.5 (3.6) vs. 15.3 (3.4), P = 0.002, A-ADHD: BIS total score 75.1 (11.3) vs. 63.4 (9.2), P < 0.001, BIS motor impulsivity 26.9 (5.3) vs. 22.6 (4.3), P < 0.001, BIS attentional score 19.3 (3.3) vs. 15.6 (3.5), P < 0.001, BIS planification 28.9 (5.7) vs. 25.10 (4.7), P = 0.003). Fifty percent of A-ADHD patients were found with high impulsivity vs. 15% of patients without A-ADHD (P < 0.001). However, ADHD was not associated with more severe addictive behavior or history of legal consequences.InterpretationADHD prevalence is high in cocaine-crack users and associated with increased impulsivity. However, neither ADHD nor impulsivity explains addictive behaviors or legal consequences.     

Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring

ObjectiveThe aim of this study was to examine the association between maternal serum vitamin D status in first trimester and risk of ASD at age 3–7 years in the offspring.MethodsUsing a case-control design, 68 children diagnosed with ASD and 68 sex and age matched typically-developing children were included. Archived maternal blood samples from the first trimester of pregnancy (11–13 weeks gestational age) were identified for those participants. Maternal serum levels of 25 hydroxyvitamin D3 [25(OH) D], unmetabolized folic acid (FA), vitamin B12, homocysteine (HCY) and High Sensitivity C Reactive protein (CRP) were measured from those samples. We examined the associations between those factors in pregnancy and diagnosis of ASD with logistic regression using SPSS.ResultsMothers in autistic group had significantly lower maternal serum levels of 25(OH) D than in typically-developing group [19.2(IQR: 15.8–22.9)ng/ml vs. 24.3(19.3–27.3)ng/ml, P < 0.001], with 55.9% and 29.4% being vitamin D deficient, respectively (P < 0.001). Levels of 25(OH) D increased with decreasing severity of ASD as defined by the CARS score (r = − 0.302, P < 0.001). Maternal first trimester serum levels of 25(OH) D in the lower 3 quartiles (quartile 1, 2, 3) (compared to the highest quartile) was associated with increased odds of ASD diagnosis in offspring [OR (95% CI) Q1: 1.36(0.84–2.58, P = 0.25); Q2: 2.68(1.44–4.29, P = 0.006); Q3:3.99(2.58–7.12, P < 0.001)].ConclusionsLower first trimester maternal serum levels of 25(OH) D were associated with increased risk of developing autism in offspring. If these findings are confirmed, this may present an opportunity for prenatal intervention to reduce the risk for ASD.     

The validity of self-rated psychotic symptoms in depressed inpatients

BackgroundSelf-ratings of psychotic experiences might be biased by depressive symptoms.MethodData from a large naturalistic multicentre trial on depressed inpatients (n = 488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale.ResultsAt discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P < 0.001) and with the BDI total score (0.64, P < 0.001). Moderate correlations were found for the MADRS (0.34, P < 0.001), HAMD (0.37, P < 0.001) and AMDP depression score (0.33, P < 0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P < 0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P < 0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P = 0.02).ConclusionsIn depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.     

Cerebral ischaemia with unknown onset: Outcome after recanalization procedure

BackgroundStroke of unknown time of onset (UTOS) accounts for one-third of contra-indications for revascularization procedures. With modern neuroimaging techniques it is possible to differentiate the core infarcts and the presence of penumbra.ObjectiveTo evaluate outcomes in patients with UTOS, treated with intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy (MT), or both.MethodWe conducted this observational study in patients treated by i.v. rt-PA, MT, or both, selected by a diffusion-weighted image/fluid-attenuated inversion recovery mismatch. We evaluated outcomes with the modified Rankin scale (mRS) at 3 months.ResultsOf 992 consecutive patients (522 women, 52.6%; median age 76 years; median baseline national institutes of health stroke scale [NIHSS] 10), 153 (15.4%) had UTOS, including 101 with wake-up strokes. Compared to other patients, they were more likely to have pre-existing mRS scores > 2 (P = 0.022), multiple infarcts (P < 0.001), middle cerebral artery occlusions (P = 0.023), and to undergo MT (P = 0.003), and less likely to receive i.v. rt-PA (P < 0.001). They had higher NIHSS scores (P < 0.001) and longer discovery to treatment initiation times (P < 0.001). They were more likely to develop pulmonary (P = 0.001) and urinary (P = 0.006) infections, and pulmonary embolism (P = 0.019), and tended to have a higher mortality rate (P = 0.052) within 7 days. After adjustment, there was no association of UTOS with any of these outcome measures anymore.ConclusionPatients with UTOS have more severe strokes and more comorbidities, but after adjustment, their outcomes did not differ from those of other patients.     

Attached to the web — harmful use of the Internet and its correlates

Background and aimsThe aim of this study was to test the validity of the Finnish version of the Internet Addiction Test and the correlates of harmful use of the Internet.MethodsOne thousand eight hundred and twenty-five students (45.5% men and 54.5% women, mean age 24.7 years, S.D. = 5.7) filled in a web-based questionnaire including IAT, reasons for use of the Internet, distress, social support, and substance use.ResultsMen had a statistically significantly higher mean score on the IAT than women. Subjects with self-reported use of cannabis had higher mean score on the IAT compared to non-users (39.5 [11.3] vs 35.8 [10.8]). The total IAT score was associated with “adult entertainment” (OR = 1.07, 95%CI: 1.06–1.08, P < 0.001), “playing games” (OR = 1.05, 95%CI: 1.04–1.06, P < 0.001), “chatting” (OR = 1.07, 95%CI: 1.06–1.08, P < 0.001) and “discussion” (OR = 1.08, 95%CI: 1.07–1.09, P < 0.001) as reasons for Internet use. The IAT score had a significant negative correlation with social support (r = ?0.24, P < 0.001) and a significant positive correlation with the CAGE score (r = 0.18, P < 0.001). Using factor analysis, we found a single factor solution with a Cronbach's α of 0.92.ConclusionsThe IAT seems to provide a valid measurement of harmful use of the Internet, as the score was significantly associated with variables tapping psychopathology.     

Can we predict intraoperative blood loss in meningioma patients? Application of dynamic susceptibility contrast-enhanced magnetic resonance imaging

PurposeTo evaluate the potential of quantitative dynamic susceptibility contrast (DSC) perfusion MR imaging parameters as imaging biomarkers for predicting intraoperative blood loss in meningioma.MethodsFifty-one non-embolized meningioma patients who had undergone preoperative DSC perfusion MR imaging were retrospectively included. The corrected relative cerebral blood volume (rCBV) and leakage coefficient (K₂) of the entire enhanced tumor were obtained using leakage correction. Tumor volume, location, grade, and other clinical variables, were also analyzed. To investigate the vascularity and vascular permeability of meningiomas, and their correlation with predicting estimated blood loss (EBL) using preoperative DSC perfusion MR imaging, the authors proposed an index reflecting the inherent tendency of meningiomas to bleed after controlling volume (i.e., EBL/cm³). Simple regression was performed to identify predictors of EBL/cm³; subsequently, the relevant variables included in the stepwise multiple linear regression.ResultsOn univariate analysis, EBL/cm³ was correlated with rCBV (r = 0.677; P < 0.001), K₂ (r = 0.294; P = 0.036), and tumor volume (r = –0.312, P = 0.026). EBL/cm³ was not correlated with age (P = 0.873), sex (P = 0.404), tumor location (P = 0.327), or histological grade (P = 0.230). On multiple linear regression, rCBV (β = 0.663 [0.463–0.864], B = 1.293 [0.903–1.684; P < 0.001) and K₂ (β = 0.260 [0.060–0.460], B = 2.277 [0.523–4.031], P = 0.012), were the only independent predictors of EBL/cm³.ConclusionThe rCBV and K₂ derived from DSC perfusion MR imaging in meningiomas may serve as feasible tools for clinicians to predict intraoperative blood loss and facilitate surgical planning.     

Anticyclic modulated ventilation versus continuous positive airway pressure in patients with coexisting obstructive sleep apnea and Cheyne–Stokes respiration: a randomized crossover trial

BackgroundAlthough coexisting obstructive sleep apnea (OSA) and Cheyne–Stokes respiration (CSR) occur frequently in patients with heart diseases, optimal treatment remains unclear. Positive airway pressure (PAP) effectively treats OSA and adaptive servo-ventilation (ASV) has been shown to improve CSR. We compared a new treatment algorithm combining automatic continuous positive airway pressure (APAP) and ASV (anticyclic modulated ventilation, ACMV) versus continuous positive airway pressure (CPAP).MethodsThirty-nine patients (35 male, four female; aged 65.5 ± 9.7 years; body mass index, 31.0 ± 5.9 kg/m²) with underlying heart disease and coexisting OSA and CSR were enrolled. After diagnostic polysomnography (PSG) and CPAP titration, patients were randomized either to CPAP or to ACMV for four weeks of treatment in a crossover design.ResultsTotal apnea–hypopnea index (AHI) was 49.0 ± 18.8/h at baseline, 12.3 ± 14.6/h with CPAP (P < 0.001 vs baseline), and 3.7 ± 5.6/h with ACMV (P < 0.001 vs baseline and vs CPAP). Obstructive AHI was 20.7 ± 14.4/h at baseline, 5.1 ± 9.3/h with CPAP (P < 0.001 vs baseline), and 0.4 ± 0.4/h with ACMV (P < 0.001 vs baseline and vs CPAP). Central AHI was 28.3 ± 13.4/h at baseline, 7.2 ± 9.7/h with CPAP (P < 0.001 vs baseline) and 3.3 ± 5.4/h with ACMV (P < 0.001 vs baseline and vs CPAP). Ejection fraction was increased significantly (from 38.6 ± 15.6 to 44.4 ± 12.2%) only with ACMV. Subjective sleepiness significantly improved only with CPAP whereas objective sleep quality and treatment adherence were not different between both treatment modalities.ConclusionACMV is an effective treatment option in patients with coexisting OSA and CSR. It is superior to CPAP in reducing total AHI as well as obstructive and central AHI.     

Is multiple sclerosis a risk factor for atherosclerosis?

BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We aimed to discuss possible predisposing factors to atherosclerosis such as carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (Hs-CRP) levels in MS.MethodsThirty-five ambulatory patients with relapsing-remitting MS (RRMS) (22 females and 13 males) and 34 healthy controls (21 females and 13 males) with similar demographic variables were included. Blood cell counts, cholesterol levels, vitamin D and B12, Hs-CRP levels, body mass index (BMI), history of smoking, and CIMT of both groups, Expanded Disability Status Scale (EDSS) scores, and disease duration of patients were recorded. Patients with a history of other vascular diseases such as hypertension, diabetes mellitus, peripheral artery disease, and acute relapses were excluded.ResultsSixty-nine participants were included. The mean age of the study population was 35.8 ± 7.1 years. Right CIMT was significantly greater in the patient population (P < 0.001). Spearman's correlation coefficient between age and right CIMT was r = 0.41, P = 0.01. When we compared the Hs-CRP with a cut-off value of ≤ 3, the right, left, and mean CIMT levels were not statistically significant (P = 0.17; P = 0.22; P = 0.15). The mean serum vitamin D levels were higher in the patient group and this was statistically significant (P < 0.001). The statistically significant factors identified with univariate analysis with P < 0.2 were further entered into multivariate modelling.ConclusionCIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Further investigation in a large MS population is still needed.     

Influence of vessel morphology and variations on technical and clinical success in mechanical thrombectomy: -In vivo and in vitro analyses-

PurposeTo determine the impact of vessel variation and anatomical features on technical and clinical success.Materials and methodsIn vitro blood clots (n = 100) were introduced into a silicon carotid-T flow model of 2, 3 or 4 mm. The ICA/M1 angle varied at 45°, 90°, 135° and 180°. Peripheral embolism was measured. In vivo 50 pat. (73.5 yrs., ± 15) with MCA occlusion were examined for siphon variation, ICA morphology, vessel diameter and angles. The patients were divided according to the clinical success (mRS): group A: mRS ≤ 2 after 90 day and group B: mRS ≥ 3. Furthermore the technical success (TICI) and number of retrieval (n) were analysed.ResultsIn vitro with larger vessel diameter the migrated thrombus load decreased (P = .001). The steeper the M1/ICA angles, the higher thrombus weighs (180°: 2.94 mg; 135°: 6.32 mg; 90°: 8.65 mg, 45°: 10.69 mg; P < .001). In vivo patients with mRS ≤ 2 had significantly lower NIHSS (16.5 vs 20, P = .009) and higher ASPECTS (9 vs 6, P < .05). TICI ≥ 2b was more often achieved (86.6 vs 40% P = .002). The procedure time was lower (45 vs. 80 min, P < .05) with smaller number of retrieval (1.5 vs 4, P < 05). Proximal ICA stenosis offers a trend to unfavourable outcome (P = .073). Siphon variation “D” is associated with less retrieval manoeuvre.ConclusionWhile in vitro there is a close correlation between embolism and vascular anatomy, in vivo carotid artery stenosis and siphon variation influence clinical and technical success.     

Rate of readmission and mortality risks of schizophrenia patients who were discharged against medical advice

PurposeTo compare the readmission and the mortality rates of schizophrenia patients who were discharged against medical advice (AMA) and patients who were discharged by physician recommendation.MethodsThe records (1984–2005) of all consecutive admissions (n = 12,937) of schizophrenia patients (n = 8,052) were reviewed. Out of this group, 673 (8.3%) refused to remain in the hospital and signed a hospital form for discharge AMA. Their records were analyzed for rates of re-hospitalization and mortality at study closure. The records of AMA patients were compared to those of patients with regular discharge (n = 1345).ResultsAMA patients were younger at admission (P < 0.001), comprised more males (P < 0.01), more were single (P < 0.0001), and had a shorter duration of illness than the controls (P < 0.05). A total of 49.9% of AMA events occurred within the first 2 weeks of hospitalization. The readmission rate was significantly higher for AMA patients than for the controls (P < 0.001). The mortality rate as a result of suicide (P < 0.0001) and accidents (P < 0.05) was higher for AMA patients compared to controls.ConclusionThe schizophrenia patients discharged AMA have a higher readmission rate and a higher mortality rate due to suicide and accidents compared to non-AMA discharged patients. Patients with AMA discharge warrant special community surveillance to improve outcome.     

Disparities in injury death location for people with epilepsy/seizures

ObjectiveWide variation has been reported in the proportion of injury deaths occurring during the prehospital phase. Potential disparities in where injured people with epilepsy and seizure disorders die have not been examined. We compared location of death between injured patients with epilepsy and seizure disorders and similar patients without epilepsy/seizures and tested the hypothesis that injured people with epilepsy/seizures are more likely to die outside of a hospital or health care setting.MethodsU.S. vital statistics (mortality) data from the multiple cause of death files of the National Center for Health Statistics were analyzed. Patients less than 65 years of age at death who had injury as the underlying cause of death were included. Multinomial logistic regression was used to assess location of death, controlling for patient and injury characteristics.ResultsControlling for potential confounders, people with epilepsy/seizures were more likely to die at home from unintentional injuries (relative risk ratio [RRR] = 1.51, P < 0.001) and less likely to die in public places (RRR = 0.27, P < 0.001). People with epilepsy/seizures were less likely to die at home or in public places from suicide, but significantly more likely to die at home from homicide (RRR = 2.29, P < 0.001). By mechanism of injury, people with epilepsy/seizures were more likely to die at home from drowning (RRR = 2.35, P < 0.001).DiscussionDisparities in where injured people with epilepsy/seizures die deserve further attention. Identifying the underlying causes of these disparities will allow for the development of targeted prevention interventions.     

A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.     

C-reactive protein as a marker of cardiovascular disease in patients with a schizophrenia spectrum disorder treated in routine medical practice

ObjectiveInterest in cardiovascular diseases (CVD) in schizophrenia has grown recently due to documented incremental mortality. C-reactive protein (CRP) has been assessed as a marker in individuals with CVD and/or at high risk of developing it. However, its role in schizophrenia patients is unknown. The goal of this research was thus to explore the use of CRP as a marker of CVD risk in patients with schizophrenia.MethodsA cross-sectional analysis of the Badalona Serveis Assistencials (BSA) administrative claims database was conducted including all subjects aged > 18 years with a diagnosis of schizophrenia spectrum disorder. CRP measurement, sociodemographics, medical history, 10-year CVD risk (Framingham function) and clinical chemistry data were extracted for analysis.ResultsSeven hundred and five patients (53.0% men, 48.2 [15.8] years, 78.7% on atypicals) met criteria for analysis. Mean 10-year CVD risk was high; 11.9 ± 5.7% and mean CRP levels were 2.6 ± 2.5 mg/L with 30.4% showing above-normative levels (> 3 mg/L). After adjusting for age, gender, smoking and presence of neoplasm or inflammatory diseases, CRP was linearly associated with 10-year CVD risk stratified by risk (low, moderate, high/very high): respectively, 2.3 (95% CI: 2.1–2.5), 3.1 (2.6–3.5) and 3.7 (3.2–4.1) mg/L; F = 13.5, P < 0.001. Patients with known CVD also showed higher CRP levels: 3.7 (2.9–4.5) vs. 2.5 (2.4–2.7) mg/L, P = 0.008; and higher probability of above-normal values; odds ratio = 4.71 (2.01–11.04), P < 0.001.ConclusionsHigh CRP levels above normative were associated with both known CVD and high/very high 10-year risk of a CVD event in patients with schizophrenia, suggesting CRP could be a marker of CVD in this psychiatric disorder.     

Body mass index variations in patients with Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion: A case control study versus standard of care and subthalamic nucleus deep brain stimulation

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion.Aims of the studyTo compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up.MethodsPatients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC).ResultsEighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (−5.8 kg ±6.8) and BMI (−2.1 kg/m² ± 2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (−1.4 kg ±3.1) and a weight increase in the STN-DBS group (5.4 kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P < 0.001), LCIG and SOC (P = 0.002) and STN-DBS and SOC (P < 0.001).ConclusionsThe study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.     

Self-referral to group cognitive behavioural therapy: Is it effective for treating chronic insomnia?

ObjectivesTo evaluate the effectiveness of a short (3 session) programme of group cognitive behavioural therapy (CBT) on insomnia, sleepiness and symptoms of anxiety and depression.MethodsProspective observational study of group CBT with follow-up at 3 months. Participants were self-referred patients with chronic insomnia. Outcome measures were the insomnia severity scale (ISI), the Epworth sleepiness scale (ESS), depression (Pichot scale), and the number of anxiety symptoms.ResultsParticipation in CBT was offered to 489 patients of whom 474 completed the programme and 154 were followed up at 3 months. Significant improvements in insomnia were seen: ISI score (17.74–14.27, P < 0.0001) after CBT and at follow-up (13.78, P < 0.0001). At the end of CBT, 76% (59/78) with initial severe insomnia and 52% (132/255) with moderate insomnia were improved, maintained at 3 months in 71% (15/21) with severe insomnia and 56% (50/90) with moderate insomnia. Depression and anxiety symptoms were significantly improved: mean depression symptoms (4.15–3.35, P < 0.0001) and anxiety symptoms (4.52–3.95, P < 0.0001), maintained at 3 months with mean depression symptoms (3.17, P < 0.0001) and mean anxiety symptoms (3.62, P < 0.0001). Sleepiness increased between baseline and the end of the group (6.67–7.24, P = 0.015) followed by a reduction at 3 months (7.19–6.34 at 3 months, P = 0.001). Initial ISI score but neither sex nor age were predictive of outcome.ConclusionsA short programme of CBT can improve sleep, depression and anxiety symptoms in self-referred patients suffering from chronic insomnia with good adherence and maximum benefit in patients with severe insomnia.