An analysis of 170 glioma patients and systematic review to investigate the association between IDH-1 mutations and preoperative glioma-related epilepsy

Seizure is a common presenting symptom of glioma, and many biomarkers have been suggested to be associated with preoperative seizure; however, the relationships between IDH (isocitrate dehydrogenase) mutations and glioma-related epilepsy only recently been studied. The authors aimed to examine the correlations between IDH mutations in glioma patients with preoperative seizures and tumor location. A series of 170 glioma samples were analyzed for IDH1 R132H mutations (amino acid change from arginine to histidine at codon 132) with immunohistochemistry (IHC) staining and for IDH mutations with direct DNA sequencing when the IHC results were negative. If either the IHC or direct DNA sequencing result was positive, the IDH status was defined as mutated. The results of the IDH mutation examinations were used to analyze the relationship between mutations and glioma-related epilepsy. The study population consisted of 64 (37.6%) World Health Organization (WHO) grade II gliomas, 58 (34.1%) grade III, and 48 (28.3%) grade IV gliomas. A total of 84 samples with IDH1 mutations were observed in our study, and 54 of these presented with seizures as the initial symptoms, whereas 28 of the patients with wild-type IDH status presented with seizures (p = 0.043 for the WHO grade II gliomas, p = 0.002 for the grade III gliomas and p = 0.942 for the grade IV gliomas, chi-squared tests). Among the WHO grade II and III gliomas, IDH1 mutations were significantly associated with preoperative seizures, but no significant relationship between IDH mutations and preoperative seizures was found with glioblastoma multiforme.     

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.     

Reliability of noncontrast-enhancing tumor as a biomarker of IDH1 mutation status in glioblastoma

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas have been associated with a frontal lobe location and a greater proportion of noncontrast-enhancing tumour (nCET). The purpose of our study was to validate the utility of MRI imaging features in predicting IDH1 mutations in glioblastomas. Pre-operative MRIs of new glioblastoma patients, consisting of at least FLAIR and T1-weighted post-contrast sequences, were reviewed by a neuroradiologist based primarily on the VASARI feature set. IDH1 mutation testing was performed on all patients using immunohistochemistry. 153 patients met the inclusion criteria, of whom five had IDH1 mutations (3.3%). A frontal lobe location had equivalent frequency in both the IDH1-mutated and IDH1-wildtype cohorts (p = 1.000). Three (60%) of the IDH1-mutated tumours had >33% nCET, compared to 21% of IDH1-wildtype (p = 0.073). 12 tumours had a frontal lobe epicentre and >33% nCET, all being IDH1-wildtype. All five IDH1-mutated tumours had either a frontal lobe epicentre or >33% nCET, but none had both these features. Our results question the strength of the association between frontal lobe glioblastomas with substantial nCET and IDH1 mutations, as these features are also relatively frequent in IDH1-wildtype tumours, which are much more common. MRI is thus more useful for ruling out an IDH1 mutation rather than strongly suggesting its presence: if a particular glioblastoma does not have a frontal lobe epicentre and has less than 33% nCET, it can be predicted to be IDH1-wildtype with a high degree of confidence.     

KPNA2 predicts long term survival in patients with anaplastic oligoastrocytomas

The family of karyopherins comprises importins and exportins which are both involved in nucleocytoplasmic shuttling. Increased levels of karyopherin a2/importin 1 (KPNA2) and chromosome region maintenance protein 1/exportin 1 (CRM1) have been associated with poorer prognosis in patients with infiltrative astrocytomas. Isocitrate dehydrogenase 1 gene (IDH1) R132H mutation status was also recently identified as a prognostic factor for malignant gliomas. We evaluated KPNA2 and CRM1, as well as the IDH1 mutation status, as possible novel biomarkers for World Health Organization grade III anaplastic oligoastrocytomas (AOA). We analyzed nuclear expression of KPNA2 by immunohistochemistry in 72 primary anaplastic gliomas (29 AOA, 24 anaplastic astrocytomas, 19 anaplastic oligodendrogliomas). The IDH1 mutation status was also determined in patients with anaplastic astrocytomas and AOA, and AOA patients were additionally evaluated for CRM1 nuclear expression. Long term survivors (LTS; >8 years) with AOA showed lower KPNA2 expression levels compared to non-LTS (p = 0.005). KPNA2 expression (⩾5% versus <5%, 1–<5%, median) was found to correlate inversely with overall survival (OS) and progression-free survival (PFS) in our overall series as well as in the AOA group (anaplastic gliomas: OS p = 0.017; PFS p = 0.033; AOA: OS p = 0.017, PFS p = 0.040). Mutant IDH1-R132H was detected in 69% of the AOA cohort; a combination of KPNA2 low expression and mutant IDH1-R132H was only seen in LTS (p = 0.050). No differences between the histological subtypes were observed in terms of KPNA2 expression and IDH1-R132H mutation status. To our knowledge this is the first time it has been shown that KPNA2 expression may have potential as a prognostic biomarker for AOA as well.     

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease

ObjectiveTo investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD).MethodsRLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1 ± 8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen.ResultsThirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5 = 59.6%; p = 0.002), worse fatigue (FSS >27 = 51%; p = 0.005), and more depressive symptoms (BDI-II >10 = 14.4%; p = 0.005). Patients with RLS also presented more severe dyspnea (p = 0.009) and lower creatinine levels (p = 0.005). Overall, fatigue severity was correlated with older age (p = 0.001); level of dyspnea was positively correlated with PSQI and FSS (p < 0.005) and negatively correlated with ferritin (p = 0.03) and creatinine (p = 0.005), and PSQI scores correlated positively with FSS (p < 0.005) and negatively with ferritin (p = 0.005) and creatinine (p = 0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression.ConclusionRLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea.     

Association between heart rate recovery and severity of obstructive sleep apnea syndrome

BackgroundObstructive sleep apnea syndrome (OSAS) is associated with autonomic dysfunction and metabolic abnormalities including obesity, dyslipidemia, and insulin resistance. Heart rate recovery at 1 min after exercise termination (HRR-1) is a marker of vagal tone. We hypothesized that patients with more severe OSAS would have a lower HRR-1, either due to the co-existing metabolic abnormalities or OSAS.MethodsSixty-three patients with untreated OSAS (49.2 ± 9.8 years) without glucose- or lipid-lowering or negatively chronotropic drugs underwent cardiopulmonary exercise testing including HRR-1 measurement and assessment of several metabolic parameters. Patients with severe OSAS (apnea–hypopnea index [AHI] > 30 h⁻¹; n = 32) were compared to patients with mild to moderate OSAS (AHI 5–30 h⁻¹; n = 31).ResultsPatients with severe OSAS were more likely to be male (25 vs. 3%; p = 0.01) and to have hypertension (72 vs. 39%; p = 0.01); they also had higher fasting glucose (5.4 ± 0.5 vs. 5.1 ± 0.4 mmol/l; p = 0.016) and C-peptide [905 (651–1353) vs. 749 (597–919) pmol/l; p = 0.028] levels compared to patients with mild to moderate OSAS. The groups did not differ with respect to peak heart rate (p = 0.2) or peak oxygen consumption (p = 0.9), but HRR-1 was significantly lower in patients with severe OSAS compared to patients with mild and moderate OSAS [20 (15–25) vs. 24 (18–34) bpm; p = 0.022]. Higher AHI (p = 0.01) and lower peak heart rate (p = 0.02), but not body mass index or insulin resistance, were independently associated with lower HRR-1.ConclusionsThe severity of OSAS expressed as higher AHI is independently associated with lower HRR-1, a measure of autonomic dysfunction.     

Predictors of response to group cognitive-behavioral therapy in the treatment of obsessive-compulsive disorder

PurposeTo identify the presence of factors associated with treatment outcome in patients under group cognitive-behavioral therapy (GCBT) for obsessive-compulsive disorder (OCD).Subjects and methodsThis study evaluated 181 patients with OCD that attended a 12-session weekly GCBT program. Response criteria were: ≥35% reduction in Y-BOCS scores and global improvement score of the Clinical Global Impression (CGI) ≤ 2 at post-treatment evaluation. Sociodemographic data, OCD characteristics, and treatment data were studied.ResultsIn the bivariate analysis, the following variables showed statistical significance (p < 0.20) to enter the regression model: being woman (p = 0.074), greater insight (p = 0.017) and better quality of life (QOL) in all domains before treatment (p = 0.053), overall severity of disease according to the CGI (p = 0.007), number of associated comorbidities (p = 0.063), social phobia (p = 0.044), and dysthymia (p = 0.072). In the final regression model, these variables were associated with response to GCBT: female gender (p = 0.021); WHOQOL-BREF psychological domain (p = 0.011); insight (p = 0.042); and global improvement score of the CGI severity-scale before therapy (p = 0.045).ConclusionSpecial attention should be paid to patients with poor insight, increasing the cognitive aspects of the therapy in an attempt to modify the rigidity and fixity of their beliefs. In addition, male patients should be more observed, since they showed lower chance of response to GCBT when compared to women. Patients with more severe global symptoms (CGI) are poorer responders to GCBT, which indicates that not only obsessive-compulsive symptoms (OCS) should be evaluated, since other symptoms, such as depression and anxiety, may affect the treatment; therefore, an attempt to reduce these symptoms, prior to the treatment of OCD, should be considered as an option in some cases.     

The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid

PurposeTo investigate the influence of vitamin B supplementation on the plasma total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical state of patients with chronic epilepsy.MethodsBeck Depression Inventory (BDI) scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2).ResultsEighty-one patients participated in the study: 51 patients with chronic epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30 patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was significantly higher in G1 than G2 (p = 0.0001) with no significant differences in s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1 patients (p = 0.00002) after 1 year of supplementation and increased in G2 after 1 year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in G1 decreased significantly after 1 year of supplementation (p = 0.0001) and increased significantly in VPA-treated G2 patients after 1 year of AED therapy (p = 0.02). The number of hyperhomocysteinemic patients significantly decreased in G1 after vitamin B supplementation (p = 0.01) and increased in G2 (p = 0.002). We also observed improved BDI scores and reduced seizure frequency in patients with chronic epilepsy.ConclusionsThese data support the hypothesis that AEDs play a major role in hyperhomocysteinemia development in patients with epilepsy. Adding folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the risk of hyperhomocysteinemia.     

BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas

BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma’s clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma’s clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p = 0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p = 0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR = 1.027, p = 0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.     

IgM-monoclonal gammopathy neuropathy and tremor: a first epidemiologic case control study

IntroductionSmall case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled.Materials and methodsAn IgM-MGUS neuropathy case cohort (n = 207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n = 414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions.ResultsTremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p = 0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p = 0.025) and demyelinating nerve conductions (p = 0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p = 0.03) but not with NIS severity (p = 0.57). Tremor occurrence associated with older age in controls, (p = 0.004) but not in IgM-MGUS cases (p = 0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p = 0.04).ConclusionsThis first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor.     

Association between depression and heart rate variability in patients after cardiac surgery: a pilot study

ObjectiveDepression is a risk factor for cardiovascular diseases. Reduced heart rate variability (HRV), which reflects altered autonomic nervous system activity, has been suggested as one of the mechanisms linking depression to cardiovascular diseases. However, the relationship between depression and HRV has not yet been investigated in patients undergone cardiac surgery. Therefore, the main aim of this study was to examine whether postoperative depression could be related to reduced HRV.MethodsEleven patients with depression and 22 patients without depression, who had undergone cardiac surgery, were enrolled postoperatively. In all patients, HRV was derived from a four-minute blood volume pulse recording at rest. Analyses of covariance and partial correlations, while controlling for anxiety, were used to examine the associations between postoperative depression and each HRV parameter.ResultsCompared to non-depressed patients, patients with depression showed significantly lower standard deviation of N-to-N intervals (SDNN) (p = .02), root mean square successive difference of N-to-N intervals (rMSSD) (p = .001), and high‐frequency power (p = .002). Partial correlation analyses showed that depression was inversely related to SDNN (r = ? .49, p = .005), rMSSD (r = ? .58, p = .001), and high‐frequency power (r = ? .41, p = .02), whereas it was unrelated to other HRV parameters (p's > .09).ConclusionsThe current findings extend the depression-reduced HRV relationship to the patients after cardiac surgery. Also, our study suggests that postoperative depression is more likely to be associated with reduced vagal modulation on the heart than with excessive sympathetic activity.     

Long-term outcome and prognosis of patients with emergent periodic lateralized epileptiform discharges (ePLEDs)

PurposeEmergent EEG (eEEG) is an EEG performed on a non-elective basis upon request from a clinician for a seemingly emergency indication. Little is known about the long-term prognosis of patients with emergent periodic lateralized epileptiform discharges (ePLEDs).MethodsWe analyzed the EEG and clinical records of patients with ePLEDs from January 2002 to December 2008.ResultsOut of 1948 eEEGs, 79 (4%) patients had ePLEDs. Sixty-three patients had ePLEDs and 16 had eBiPLEDs (emergent bilateral periodic lateralized epileptiform discharges). The etiology of ePLEDs was CNS infection and inflammation (35.4%), stroke (32.9%), and metabolic encephalopathy (11.4%). Of the surviving 52 (65.8%) patients with ePLEDs, 34 (65.4%) had persistent seizures during a mean follow-up of 28 months (range 12–72 months). Seizure as the initial presentation was more commonly seen in children as compared to adults (64% versus 31%, p = 0.005). CNS infection and inflammation were also seen more frequently in the pediatric age group (50% versus 27%, p = 0.04). At follow-up, patients with eBiPLEDs had more seizures than patients with ePLEDs (87.5% versus 61.3%).ConclusionePLEDs is associated with significant morbidity and mortality. However, the etiology of ePLEDs and brain dysfunction will influence the long-term outcome. This information is invaluable for prognostication and underscores the importance of rigorous management of patients with ePLEDs.     

Genome-wide study identifies PTPRO and WDR72 and FOXQ1-SUMO1P1 interaction associated with neurocognitive function

BackgroundSeveral aspects of neurocognitive function have high heritability, but the molecular genetic mechanisms underlying neurocognition are not known. We performed a genome-wide association study (GWAS) to identify genes associated with neurocognition.Methods700 Subjects (schizophrenia spectrum disorder, n = 190, bipolar disorder n = 157 and healthy individuals n = 353) were tested with an extensive neuropsychological test battery, and genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0. After quality control, linear regression analysis of each of the 24 cognitive tests on the SNP dosage was performed, including age, gender, education and disease group as covariates. Additionally, 9 SNPs trending toward genome-wide significance were considered for epistatic interactions.ResultsFour SNPs and 2 independent association signals achieving genome-wide significance were identified. Three intronic SNPs in PTPRO were associated with learning and memory (CVLT-II LDFR) (rs17222089, p = 1.55 × 10^?8; rs11056571, p = 1.68 × 10^?8; and rs2300290, p = 1.09 × 10^?8). rs719714 downstream of WDR72 was associated with executive functioning (CW-3: Inhibition, D-KEFS) (p = 4.32 × 10^?8). A highly significant epistatic interaction was found between rs9378605 upstream of FOXQ1 and rs11699311 downstream of SUMO1P1 for the Grooved Pegboard test (p = 7.6 × 10^?14).ConclusionsWe identified four novel loci associated with neurocognitive function and one novel epistatic interaction. The findings should be replicated in independent samples, but indicate a role of PTPRO in learning and memory, WDR72 with executive functioning, and an interaction between FOXQ1 and SUMO1P1 for psychomotor speed.     

Outcomes of Thai patients with acute ischemic stroke after intravenous thrombolysis

The purpose of this study was to assess outcomes in Thai patients after treatment with intravenous recombinant tissue plasminogen activator (rtPA) and to determine the factors associated with good outcome and death.MethodsPatients with acute ischemic stroke who were treated with intravenous rtPA at Thammasat University Hospital between June 2007 and April 2010 were included. The measured outcome variables were good outcome (mRS 0,1) and death at 3 months. Stepwise multivariable analyses were performed by including the prespecified factors that were associated with the measured outcome variables in the univariate analysis.ResultsThe sample size was 197 patients. At 3 months, 93 patients (47%) had good outcomes while 23 patients (12%) died within the same period. Severe stroke (OR 0.19, 95% CI 0.08–0.44, p-value < 0.0001) and history of hypertension (OR 0.39, 95% CI 0.16–0.93, p-value = 0.033) were independently related to bad outcome at 3 months, while receiving intravenous nicardipine (OR 2.76, 95% CI 1.09–6.94, p-value = 0.032) was associated with good outcome. Severe stroke (OR 5.89, 95% CI 1.29–26.85, p-value = 0.022) and pretreatment high blood glucose levels (OR 8.06, 95% CI 1.21–53.62, p-value = 0.031) each were independently associated with patient death.ConclusionsStandard-dose intravenous rtPA in a cohort of Thai patients led to better clinical outcomes and comparable death rates when compared to other Asian cohorts receiving intravenous rtPA. Several factors were independently associated with patient outcomes at 3 months.     

Sleep-disordered breathing and chronic atrial fibrillation

BackgroundLittle has been known about the prevalence of sleep apnea in patients with atrial fibrillation (AF). Studies have suggested that the prevalence of AF is increasing in patients with sleep-disordered breathing. We hypothesize that the prevalence of OSA is higher in chronic persistent and permanent AF patients than a sub-sample of the general population without this arrhythmic disorder.ObjectiveEvaluate the frequency of Obstructive Sleep Apnea in a sample of chronic AF compared to a sub-sample of the general population.MethodsFifty-two chronic AF patients aged (60.5 ± 9.5, 33 males) and 32 control (aged 57.3 ± 9.6, 15 males). All subjects were evaluated by a staff cardiologist for the presence of medical conditions and were referred for polysomnography. The differences between groups were analyzed by ANOVA for continuous variables, and by the Chi-square test for dichotomous variables. Statistical significance was established by α = 0.05.ResultsThere were no differences in age, gender, BMI, sedentarism, presence of hypertension, type 2 diabetes mellitus, abdominal circumference, systolic and diastolic blood pressure, and sleepiness scoring between groups. Despite similar BMI, AF patients had a higher neck circumference compared to control group (39.9 cm versus 37.7 cm, p = 0.01) and the AF group showed higher percentage time of stage 1 NREM sleep (6.4% versus 3.9%, p = 0.03).Considering a cut-off value for AHI ? 10 per hour of sleep, the AF group had a higher frequency of OSA compared to the control group (81.6% versus 60%, p = 0.03). All the oxygen saturation parameters were significantly worse in the AF group, which had lower SaO₂ nadir (81.9% versus 85.3%, p = 0.01) and mean SaO₂ (93.4% versus 94.3%, p = 0.02), and a longer period of time below 90% (26.4 min versus 6.7 min, p = 0.05).ConclusionSleep-disordered breathing is more frequent in chronic persistent and permanent AF patients than in age-matched community dwelling subjects.     

Clinical significance of night-to-night sleep variability in insomnia

ObjectivesTo evaluate the clinical relevance of night-to-night variability of sleep schedules and insomnia symptoms.MethodsThe sample consisted of 455 patients (193 men, mean age = 48) seeking treatment for insomnia in a sleep medicine clinic. All participants received group cognitive behavioral therapy for insomnia (CBTI). Variability in sleep parameters was assessed using sleep diary data. Two composite scores were computed, a behavioral schedule composite score (BCS) and insomnia symptom composite score (ICS). The Insomnia Severity Index, the Beck Depression Inventory, and the Morningness–Eveningness Composite Scale were administered at baseline and post-treatment.ResultsResults revealed that greater BCS scores were significantly associated with younger age, eveningness chronotype, and greater depression severity (p < 0.001). Both depression severity and eveningness chronotype independently predicted variability in sleep schedules (p < 0.001). Finally, CBTI resulted in reduced sleep variability for all sleep diary variables except bedtime. Post-treatment symptom reductions in depression severity were greater among those with high versus low baseline BCS scores (p < 0.001).ConclusionsResults suggest that variability in sleep schedules predict reduction in insomnia and depressive severity following group CBTI. Schedule variability may be particularly important to assess and address among patients with high depression symptoms and those with the evening chronotype.     

Cannabis use and age of diagnosis of schizophrenia

Background and objectivesObservational studies have reported earlier onset of psychosis in schizophrenic patients with a history of cannabis use. Earlier age of onset of schizophrenia has been associated with a poorer outcome. We aimed to examine whether cannabis use determined an earlier onset of schizophrenia in a sample of first episode patients, in an area with one of Europe's highest rates of cannabis use.Methods116 subjects with first episode psychosis and subsequent diagnosis of schizophrenia (after a 12-month follow-up) were included Age at first antipsychotic treatment (A1T) was used as proxy for age of psychosis onset, and acted as dependent variable for the statistical analysis. Cannabis use was evaluated retrospectively, and divided into three groups according to peak frequency (never, sporadic/frequent, daily).Results46 (39.7%) subjects had never used cannabis, 23 (19.9%) had done so sporadically/frequently, and 47 (40.5%) daily. A1T differed between the three groups (mean, in years and [SD]: 27.0 [4.94]; 25.7 [4.44] and 24.5 [4.36]; p = 0.033) and diminished as cannabis use increased (linear tendency; p = 0.009). Post-hoc analysis showed that cannabis use (irrespective of frequency) was significantly associated with decrease in A1T (p = 0.033), as shown by the first contrast [1 ?1/2 ?1/2]. Post-hoc contrast showed that cannabis users had a significantly lower age of onset of psychosis (mean decrease, in years: 1.93; CI (confidence interval) 95%: 0.17–3.70; p = 0.033).ConclusionsCannabis use was significantly associated with a decrease in age of onset of schizophrenia. Age of onset of the disease correlated with frequency of cannabis use.     

Educational attainment and mean leukocyte telomere length in women in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study

BackgroundTelomere length has been postulated as a marker of biological aging. Recent evidence has suggested that educational attainment but not social class is associated with telemore length.MethodsWe investigated the associations between educational attainment, social class and relative mean telomere length in an ethnically homogeneous population of 4441 women, aged 41–80 years. Mean telomere length was measured using high-throughput quantitative Real Time PCR.ResultsEducational attainment (p = 0.015) but not social class (p = 0.61) was associated with mean telomere length in these data. This association was independent of social class and of systolic blood pressure, high-density lipoprotein cholesterol, cigarette smoking, body mass index, glycated hemoglobin, plasma vitamin C and physical activity (p = 0.014), and was not attenuated through additional adjustment for measures of social adversity, including those experienced during childhood (p = 0.006).ConclusionsOur results, at least for women, provide support for the findings previously reported in this journal that lower educational attainment, but not social class, is associated with shorter telomere length.     

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: Results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR)

BackgroundThe electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice.MethodsParameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n = 1345) or a new oral antipsychotic (AP) (n = 277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review.ResultsAt 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p < 0.0001) and reduction in Clinical Global Impression Severity scores (?1.14 for RLAI versus ?0.94 for APs, p = 0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p < 0.05) and days (18.74 versus 13.02, p < 0.01) of hospitalizations at 24 months than oral AP patients.ConclusionsThis 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.     

Performance of the Mood Disorder Questionnaire (MDQ) according to bipolar subtype and symptom severity

ObjectiveTo evaluate the performance of the French version of the Mood Disorder Questionnaire (MDQ) in patients attending a general psychiatric outpatient service as well as whether MDQ scores are independent of patient mood state at time of completion.Method183 patients completed the MDQ and were assessed with the MADRS and YMRS scales, before being interviewed with the SCID (time 1). MDQ, MADRS and YMRS assessment was repeated four to six weeks later (time 2).ResultsAccording to the SCID, 44 patients were suffering from bipolar spectrum disorder and 102 from unipolar disorder (37 patients dropped out). The MDQ provided high specificity (83.3%). Sensitivity was 63.6%, with better identification of bipolar I (85.0%) than bipolar II patients (45.8%). In the whole sample, test-retest reliability was satisfactory (kappa = 0.64). Modest correlations were observed between the number of endorsed MDQ items and YMRS scores at time 1 (Spearman r = 0.19; p = 0.021) and time 2 (r = 0.26; p = 0.002).ConclusionsDespite some fluctuations over time and a discrete influence of symptom severity, the screening algorithm can be used reliably, whether in the acute or remission phase of a depressive episode.