Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases

IntroductioStereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases.Patients and methodsWe performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression.ResultsWe identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p < 0.0001), and thus larger V100% (p < 0.0001), V50% (p < 0.0001), V12 Gy (p < 0.0001), and V10 Gy (p = 0.0002), compared to the rest of the cohort. Single-fraction treatment (p = 0.0025) and diabetes (p = 0.019) were also significantly associated with symptomatic RN.ConclusionSRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12 Gy, or V10 Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.     

Psychosocial and sociodemographic associates of felt stigma in epilepsy

BackgroundLack of a sufficient range in socioeconomic status (SES) in most prior studies of felt stigma and epilepsy has hampered the ability to better understand this association.MethodsWe assessed the burden and associates of felt stigma in 238 individuals with prevalent epilepsy aged 18 and older, comparing low SES with high SES.ResultsReported levels of stigma were higher in low SES than in high SES (p < 0.0001), and all psychosocial variables were associated with stigma, including depression severity (p < 0.0001), knowledge of epilepsy (p = 0.006), quality of life (p < 0.0001), social support (p < 0.0001), and self-efficacy (p = 0.0009). Stigma was statistically significantly associated with quality of life in the low SES group and with depression severity and social support in the high SES group.ConclusionsLow SES alone did not account for felt stigma; rather, we found that quality of life, depressive symptoms, and social support have the greatest impact on reported felt stigma in individuals with prevalent epilepsy.     

Handedness,eyedness, and hand–eye crossed dominance in patients with different addictions

ObjectiveSome neurologic and psychiatric disorders such as schizophrenia, depression, autism and migraine are referred to as cerebral lateralization abnormalities. In this study the possible relationships among handedness, eye dominance, and crossed hand–eye dominance in patients with different addictions mentioned above are investigated.MethodsThirty three patients with cigarette, 35 patients with alcohol, 133 patients with heroin, 117 patients with hashish, 13 patients with drug addictions and 102 age matched controls were included in the study. Six of 13 patients with drug addictions were addicted to diazepam, 5 to pethidine and 2 to clonazepam. The patient group included 307 men and 24 women who ranged in age from 15 to 70 years. Handedness was ascertained by using the Edinburgh Handedness Inventory. Eye dominance was measured only by the near-far alignment test. Diagnoses were made on the basis of information provided from clinical interviews and Structured Clinical Interview for DSM-IV.ResultsPatients with heroin and hashish had a significantly increased frequency of left-handedness in comparison with the other patients and controls (chi square = 29.36, p < 0.001). Patients with cigarette, alcohol, heroin and hashish addictions had a significantly increased frequency of left-eyedness in comparison with controls (chi square = 25.24, p < 0.01). Also, patients with cigarette, alcohol, heroin and hashish addictions had a significantly increased frequency of the crossed hand–eye dominance in comparison with controls (chi square = 19.11, p < 0.01).ConclusionsDifferent addictions such as cigarette, alcohol, heroin and hashish may be associated with abnormal handedness distribution and accepted as cerebral lateralization abnormalities.     

Efficacy and safety of doxepin 6 mg in a model of transient insomnia

IntroductionThe efficacy and safety of doxepin (DXP) 6 mg tablets were evaluated in healthy adults in a model of transient insomnia.MethodsThis was a randomized, double-blind, parallel-group, placebo-controlled study in healthy adults using a model of transient insomnia. A first-night effect combined with a 3-h phase advance was implemented to induce transient insomnia in healthy adults. Subjects received a single night time dose of placebo (PBO; N = 282) or DXP 6 mg (N = 283) in a sleep laboratory. Efficacy was evaluated objectively (polysomnography; PSG) and subjectively (morning questionnaire). Consistent with the model utilized, the primary endpoint was latency to persistent sleep (LPS); secondary PSG endpoints included wake after sleep onset (WASO; key secondary endpoint), total sleep time (TST), wake time after sleep (WTAS) and sleep efficiency (SE; overall, by quarter of the night and hourly); secondary subjective endpoints included latency to sleep onset (LSO), subjective WASO (sWASO), subjective TST (sTST) and sleep quality.ResultsDXP 6 mg demonstrated statistically significant improvements in LPS (13 min decrease versus PBO; p < 0.0001), WASO (39 min less than PBO; p < 0.0001), TST (51 min more than PBO; p < 0.0001), WTAS (p < 0.0001), overall SE (p < 0.0001), SE in each quarter of the night (p < 0.0001) and SE in each of the 8 h (p ? 0.0003), all versus PBO. Additionally, DXP 6 mg significantly improved subjective variables including LSO (p < 0.0001), sWASO (p = 0.0063), sTST (p < 0.0001), and sleep quality (p = 0.0004), versus PBO. There was no consistent evidence of next-day residual sedation and also minor sleep stages alterations. The incidence of adverse events was comparable to placebo.ConclusionsIn this model of transient insomnia, DXP 6 mg demonstrated significant improvements in sleep onset, sleep maintenance, sleep duration and sleep quality, and also appeared to reduce early morning awakenings. These data suggest that DXP 6 mg may be effective and well tolerated in adults experiencing transient insomnia.     

Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry

PurposeThe aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category.MethodsRetrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories.ResultsMore women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (p < 0.0001). The risk ratio for seizure increase on hormonal (18.7%) versus nonhormonal contraception (4.2%) was 4.47 (p < 0.0001). The risk ratio for seizure decrease on hormonal (9.5%) versus nonhormonal contraception (5.5%) was 1.71, p < 0.0001. On hormonal contraception, the risk ratio for seizure increase was greater than for decrease (1.98, p < 0.0001). In comparison to combined pills, both hormonal patch and progestin-only pills had greater risk ratios for seizure increase. Depomedroxyprogesterone was the only hormonal method with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (p < 0.001). On hormonal contraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio = 2.53, p = 0.0002).ConclusionThe findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category.     

When is electrical cortical stimulation more likely to produce afterdischarges?

ObjectiveTo study when afterdischarges (ADs) are more likely to occur during cortical stimulation.MethodsWe examined 6250 electrical stimulation trials in 13 patients with subdural electrodes, studying whether AD occurrence during a trial was influenced by electrode pair stimulated or AD occurrence during the previous trial. In total 545 electrodes were stimulated, 119 frontal (pre-perirolandic), 289 perirolandic, 36 parietal (post-perirolandic), 95 temporal, and 6 occipital.ResultsWhen the same electrode pair was stimulated as the prior trial, 19% produced ADs compared to 5% of trials when a different electrodes pair was stimulated (p < 0.0001). When trials showed ADs, and the next trial stimulated the same electrode pair, ADs occurred in 46% of cases, compared to 13% of trials following trials without ADs (p < 0.0001). AD probability decreased with increased inter-trial interval length only when the prior trial was at the same electrode pair and had produced an AD (p = 0.001). AD probability increased with stimulation duration, whether the trial followed a trial with (p < 0.001) or without (p < 0.0001) an AD.ConclusionsADs were more likely to occur when an electrode pair showed ADs and was stimulated again, especially when stimulating after short inter-trial intervals or for longer duration.SignificanceWhen ADs occur, waiting about a minute before resuming stimulation might lessen the likelihood of AD recurrence.     

In-hospital outcomes of aneurysmal subarachnoid hemorrhage associated with cocaine use in the USA

Cocaine use is associated with higher mortality in small retrospective studies of brain-injured patients. We aimed to explore in-hospital outcomes in a large population based study of aneurysmal subarachnoid hemorrhage (aSAH) with cocaine use. aSAH patients were identified from the 2007–2010 USA Nationwide Inpatient Sample using International Classification of Disease, Ninth Revision codes. Demographics, comorbidities and surgical procedures were compared between cocaine users and non-users. The primary outcomes were in-hospital mortality and home discharge/self-care. Secondary outcomes were vasospasm treated with angioplasty, hydrocephalus, gastrostomy and tracheostomy. There were 103,876 patients with aSAH. The cocaine group were younger (45.8 ± 9.8 versus 58.4 ± 15.8, p < 0.001), predominantly male (53.3% versus 38.5%, p < 0.001) and had a higher proportion of black patients (36.9% versus 11.5%, p < 0.001). The incidence of seizures was higher among cocaine users (16.2% versus 11.1%, p < 0.001). Endovascular coiling of intracranial aneurysms (24% versus 18.5%, p < 0.001) was more frequent in cocaine users. The univariate analysis showed higher rates of in-hospital mortality and vasospasm treated with angioplasty, but lower home discharge in the cocaine group. In the multivariate analysis, the cocaine cohort had higher in-hospital mortality (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.27–1.61, p < 0.001) and lower home discharge rates (OR 0.79, 95% CI 0.69–0.87, p < 0.001) after adjusting for confounders. Rates of vasospasm treated with angioplasty however were similar between the two groups. Cocaine use was found to be independently associated with poor outcomes, particularly higher mortality and lower home discharge rates. Cocaine use however, was not associated with vasospasm that required treatment with angioplasty. Prospective confirmation is warranted.     

Insight in schizophrenia–course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder

BackgroundTo analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight.MethodsInsight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale (“lack of insight and judgement”). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients.ResultsAlmost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p < 0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p = 0.0004), less suicidality (p = 0.0218), suffering from multiple illness-episodes (p < 0.0001) and worse adherence (p = 0.0012) at admission were identified to be significant predictors of poor insight at discharge.ConclusionThe revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.     

Cortical processing during smartphone text messaging

ObjectiveThe objective of this study was to report the EEG features of text messaging using smartphones.MethodsOne hundred twenty-nine patients were prospectively evaluated during video-EEG monitoring (VEM) over 16 months. A reproducible texting rhythm (TR) present during active text messaging with a smartphone was compared with passive and forced audio telephone use, thumb/finger movements, cognitive testing/calculation, scanning eye movements, and speech/language tasks in patients with and without epilepsy. Statistical significance was set at p < 0.05.ResultsTwenty-seven patients with a TR were identified from a cohort of 129 (93 female, mean age: 36; range: 18–71) unselected VEM patients. Fifty-three out of 129 patients had epileptic seizures (ES), 74/129 had nonepileptic seizures (NES), and 2/129 were dual-diagnosed. A reproducible TR was present in 27/129 (20.9%) specific to text messaging (p < 0.0001) and present in 28% of patients with ES and 16% of patients with NES (p = NS). The TR was absent during independent tasks and audio cellular telephone use (p < 0.0001). Age, gender, epilepsy type, MRI results, and EEG lateralization in patients with focal seizures were unrelated (p = NS).ConclusionsOur results suggest that the TR on scalp EEG represents a novel technology-specific neurophysiological alteration of brain networks. We propose that cortical processing in the contemporary brain is uniquely activated by the use of PEDs.SignificanceThese findings have practical implications that could impact industry and research in nonverbal communication.     

Factors associated with lack of response to valproic acid monotherapy in juvenile myoclonic epilepsy

PurposeTo determine factors associated with lack of response to valproic acid (VPA) in juvenile myoclonic epilepsy (JME).MethodRetrospective analysis of clinical and EEG data of 201 patients with JME who had at least 3 years follow up was performed. Psychiatric evaluation was performed using ICD-10 by structured clinical interview. Patients were divided into two groups: VPA responders (seizure free for 2 or more years) and those with lack of response to VPA. Effect size for non-response and correlations for variables significantly different between the groups was performed, the findings were confirmed by ROC curves.ResultsThe mean duration of follow up was 7.75 (range 3–12) years; 55.2% were males. Focal semiologic features were noted is 16%. EEG was abnormal in 67%; focal EEG abnormalities were noted in 32.8%. Coexisting psychiatric disorders (PDs) were found in 33.3%. Lack of response to VPA was noted in 19%. Diagnosis of PDs and focal EEG abnormalities significantly increased the risk of VPA non-responsiveness by 5.54 (95% CI of 2.60–11.80; p < 0.0001) and 3.01 times respectively (95% CI of 1.40–6.47; p < 0.008). Diagnosis of PDs showed significant correlation (r = 0.332; p < 0.0001) and association (AUC 0.700; p < 0.0001) with lack of response to VPA. Though focal EEG abnormalities increased the chances, it did not correlate with lack of response to VPA.ConclusionLack of response to VPA was noted 19% of patients with JME. Coexisting PDs showed significant correlation and association with lack of response to VPA.     

Effects of ebselen versus nimodipine on cerebral vasospasm subsequent to experimental subarachnoid hemorrhage in rats

We investigated the effect of ebselen relative to nimodipine in an animal model of subarachnoid hemorrhage. Thirty Wistar albino rats were divided into 5 groups: G1, no intervention; G2, sham surgery without subarachnoid hemorrhage (SAH); G3, SAH only; G4, SAH plus nimodipine treatment; G5, SAH plus ebselen treatment. For G2 animals, physiological saline (0.9% NaCl) was injected into the cisterna magna. For G3, G4 and G5 animals, SAH was induced by injecting autologous non-heparinized blood into the cisterna magna. One hour after injection, G4 animals received nimodipine at 6-hour intervals and G5 animals received ebselen twice a day for 48 hours. After treatment, brain tissue and blood samples were taken for biochemical and histopathological examination. Mean malonyldialdehyde concentration was significantly higher in G3 than in G1 (p < 0.0001), G2 (p = 0.01), G4 (p = 0.002) and G5 (p = 0.014), and significantly higher in G5 than in G1 (p = 0.013). Mean superoxide dismutase activity was significantly lower in G4 than in both G1 (p = 0.025) and G2 (p = 0.02). Mean wall thickness was significantly greater in G3 than in G1 (p < 0.0001), G2 (p = 0.01), G4 (p < 0.0001) and G5 (p < 0.0001). Mean wall thickness was also significantly greater in both G1 and G2 than in G4 (p < 0.0014 and p < 0.0001) and G5 (p < 0.0001 and p < 0.0001). Mean luminal diameter of the basilar artery was significantly smaller in G3 than in G2 (p = 0.02), G4 (p < 0.018) and G5 (p < 0.001). Our results confirm that ebselen may have neuroprotective effects by acting to prevent vasospasm.     

The Burden of Narcolepsy Disease (BOND) study: health-care utilization and cost findings

ObjectivesThe aim of this study was to characterize health-care utilization, costs, and productivity in a large population of patients diagnosed with narcolepsy in the United States.MethodsThis retrospective, observational study using data from the Truven Health Analytics MarketScan® Research Databases assessed 5 years of claims data (2006–2010) to compare health-care utilization patterns, productivity, and associated costs among narcolepsy patients (identified by International Classification of Diseases, Ninth Revision (ICD9) narcolepsy diagnosis codes) versus matched controls. A total of 9312 narcolepsy patients (>18 years of age, continuously insured between 2006 and 2010) and 46,559 matched controls were identified.ResultsCompared with controls, narcolepsy subjects had approximately twofold higher annual rates of inpatient admissions (0.15 vs. 0.08), emergency department (ED) visits w/o admission (0.34 vs. 0.17), hospital outpatient (OP) visits (2.8 vs. 1.4), other OP services (7.0 vs. 3.2), and physician visits (11.1 vs. 5.6; all p < 0.0001). The rate of total annual drug transactions was doubled in narcolepsy versus controls (26.4 vs. 13.3; p < 0.0001), including a 337% and 72% higher usage rate of narcolepsy drugs and non-narcolepsy drugs, respectively (both p < 0.0001). Mean yearly costs were significantly higher in narcolepsy compared with controls for medical services ($8346 vs. $4147; p < 0.0001) and drugs ($3356 vs. $1114; p < 0.0001).ConclusionsNarcolepsy was found to be associated with substantial personal and economic burdens, as indicated by significantly higher rates of health-care utilization and medical costs in this large US group of narcolepsy patients.     

Predicting long-term outcome in poor grade aneurysmal subarachnoid haemorrhage patients utilising the Glasgow Coma Scale

The Glasgow Coma Scale (GCS) is the most universally accepted system for grading level of consciousness. Predicting outcome is particularly difficult in poor grade aneurysmal subarachnoid haemorrhage (aSAH) patients. We hypothesised that the GCS and individual examination components would correlate with long-term outcome and have varying prognostic value depending on assessment time points. GCS scores of 160 aSAH patients presenting in stupor or coma were prospectively recorded on admission and each subsequent day until hospital day 14. Early treatment was planned for each patient unless the patient’s family refused aggressive intervention or the patient died before surgery. Outcomes were assessed by the modified Rankin scale (mRS) at 14 days, 3 months, and one year.All patients who did not receive surgical treatment died within one year. Of the 104 patients who received surgical treatment, 13.5% of them had a favourable outcome at 14 days, 38.5% at 3 months, and 51% at one year (p < 0.0001). Admission GCS scores significantly correlated with outcome (Spearman rank test, rs = 0.472, p < 0.0001). On admission, motor examination correlated best with one-year outcome (rs = 0.533, p < 0.0001). Each point increase in motor examination predicted a 1.8-fold increased odds of favourable long-term outcome (95% confidence interval [CI], 1.4–2.3). At discharge, eye examination (rs = 0.760, p < 0.0001) correlated best with one-year outcome, and a one point increase in eye examination predicted a 3.1-fold increased odds of favourable outcome (95% CI, 1.8–5.4). During hospitalisation, the best eye exam (rs = 0.738, p < 0.0001) and worst motor exam (rs = 0.612, p < 0.0001) were the most highly correlated with the one-year outcome.Long-term follow-up is necessary when evaluating recovery after aSAH, as outcomes improve significantly during the first year. The GCS and its individual components correlate well with long-term outcome. Admission motor examination and spontaneous eye opening during hospitalisation are most predictive of favourable recovery.     

Afferent control of walking: Are there distinct deficits associated to loss of fibres of different diameter?

ObjectivesTo compare the gait pattern in patients affected by different types of neuropathy.MethodsWe recruited healthy subjects (HS, n = 38), patients with Charcot–Marie–Tooth disease type 1A (CMT1A) (n = 10) and patients with diabetic neuropathy (DNP) (n = 12). Neuropathy impairment score and neuropathy score were assessed. Body sway during quiet stance, and spatio-temporal gait parameters were recorded.ResultsMost patients had reduced or absent tendon-tap reflexes. Strength of foot dorsiflexor muscles (p < 0.05) and conduction velocity (CV) of leg nerves (p < 0.0001) were more impaired in CMT1A than DNP, whereas joint-position sense was more affected (p < 0.05) in DNP. Body sway while standing was larger in DNP compared to CMT1A and HS (p < 0.01 and p < 0.0001 respectively). During gait, the distribution of foot sole contact pressure was abnormal in CMT1A (p < 0.05) but not in DNP. Velocity and step length were decreased, and foot yaw angle at foot flat increased, in DNP with respect to CMT1A and HS (both variables, p < 0.001). Gait velocity and step length were decreased (p < 0.005) also in CMT1A, but to a smaller extent than in DNP, so that the difference between patient groups was significant (p < 0.0005). Duration of the double support was protracted in DNP compared to CMT1A and HS (p < 0.0005). For DNP only, velocity of gait and duration of single support were correlated (p < 0.05) both to sway path and lower limb muscle strength.ConclusionsChanges in both body sway and stance phase of gait were larger in DNP than CMT1A, indicating more impaired static and dynamic control of balance when neuropathy affects the small in addition to the large afferent fibres. Diminished somatosensory input from the smaller fibres rather than muscle weakness or foot deformity plays a critical role in the modulation of the support phase of gait.SignificanceThe analysis of balance and gait in patients with neuropathy can offer a tool for understanding the nature and functional impact of the neuropathy and should be included in their functional evaluation.     

Suicidal risk among patients enrolled in methadone maintenance treatment: HCV status and implications for suicide prevention (ANRS Methaville)

BackgroundSuicide is a critical issue among opioid users. The aim of this study was to assess the relationship between HCV status and suicidal risk in patients receiving methadone treatment.MethodsWe used data from Methaville, a multicenter, pragmatic randomized trial designed to evaluate the feasibility of methadone induction in primary care compared with induction in specialized centers. Suicidal risk was assessed at enrollment and after one year of methadone treatment using the suicidality module in the MINI International Neuropsychiatric Interview. Socio-demographic characteristics, drug and alcohol consumption, behavioral and personality factors, history of drug use and health indicators were also assessed.ResultsA total of 195 individuals were enrolled from January 2009 to December 2010. Suicidal risk assessment was available at month 0 (M0) and M12 for 159 (72%) and 118 (73%) individuals, respectively. Forty-four (28%) were at risk of suicide at M0 and 17 (14%) at M12 (p = 0.004). One patient attempted suicide by overdose during the one-year follow-up. The following three factors were associated with suicidal risk: hepatitis C virus (HCV) positive status (OR [95%CI] = 17.25 [1.14–161.07]; p = 0.04), receiving food assistance (OR [95%CI] = 0.05 [0.00–1.05]; p = 0.05) and a higher number of health problems (OR [95%CI] = 1.24 [1.08–1.44]; p = 0.003).ConclusionsSpecial attention should be given to HCV-positive patients through suicidal risk prevention strategies and routine suicide assessment as part of a comprehensive approach to prevention and care for opioid users. Our results represent a new and powerful argument for the expansion of access to HCV treatment to drug users with chronic infection.     

Airflow limitations in pregnant women suspected of sleep-disordered breathing

Background and aimPregnancy physiology may predispose women to the development of airflow limitations during sleep. The goal of this study was to evaluate whether pregnant women suspected of sleep-disordered breathing (SDB) are more likely to have airflow limitations compared to non-pregnant controls.MethodsWe recruited pregnant women referred for polysomnography for a diagnosis of SDB. Non-pregnant female controls matched for age, body mass index (BMI), and apnoea–hypopnoea index (AHI) were identified from a database. We examined airflow tracings for changes in amplitude and shape. We classified airflow limitation by (a) amplitude criteria defined as decreased airflow of ⩾10 s without desaturation or arousal (FL 10), or decreased airflow of any duration combined with either 1–2% desaturation or arousal, (FL 1–2%); and (b) shape criteria defined as the presence of flattening or oscillations of the inspiratory flow curve.ResultsWe identified 25 case-control pairs. Mean BMI was 44.0 ± 6.9 in cases and 44.1 ± 7.3 in controls. Using shape criteria, pregnant women had significantly more flow-limited breaths throughout total sleep time (32.4 ± 35.8 vs. 9.4 ± 17.9, p < 0.0001) and in each stage of sleep (p < 0.0001) than non-pregnant controls. In a subgroup analysis, pregnant women without a diagnosis of obstructive sleep apnoea (OSA) who had an AHI <5 had similar findings (p < 0.0001). There was no difference in airflow limitation by amplitude criteria between pregnant women and controls (p = 0.22).ConclusionsPregnant women suspected of OSA have more frequent shape-defined airflow limitations than non-pregnant controls, even when they do not meet polysomnographic OSA criteria.     

Treatment of elderly primary insomnia patients with EVT 201 improves sleep initiation,sleep maintenance,and daytime sleepiness

ObjectiveTwo doses of EVT 201, a partial positive allosteric modulator of the GABA_A system, were evaluated in elderly primary insomnia patients with daytime sleepiness.Patients and methodsParticipants were 149 elderly patients with DSM-IV primary insomnia including evidence of daytime sleepiness (53 males, 96 females; mean age 71.3 yrs, range 65–86 yrs). A randomized, multicentre, double-blind, placebo-controlled, parallel-group design was used to assess the hypnotic efficacy of EVT 201 1.5 and 2.5 mg during seven consecutive nights. Polysomnography (PSG) was performed on nights 1, 6 and 7 of treatment. Daytime assessments on Day 8 included the multiple sleep latency test (MSLT), Rey Auditory Verbal Learning Test (RAVLT), Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS). The primary endpoint was total sleep time (TST) and the key secondary endpoint was mean MSLT latency.ResultsCompared to placebo, EVT 201 1.5 and 2.5 mg increased TST (30.9, 56.4 min, respectively; p = 0.0001, p < 0.0001); reduced wake after sleep onset (WASO; ?15.2, ?36.1 min, respectively; p = 0.014, p < 0.0001); reduced latency to persistent sleep (LPS; ?15.9, ?19.9 min, respectively; p = 0.009, p = 0.001). The 2.5 mg dose also reduced WASO in hours 5–8 (?16.3 min, p = 0.001). Both doses also improved subjective sleep quality and usual subjective efficacy measures. A significantly longer mean MSLT latency was observed on Day 8 with both doses, compared to placebo (2 min increase; p = 0.03, both doses). The PVT, RAVLT, and POMS did not differ among treatment groups. No serious or unexpected treatment emergent adverse events were noted.ConclusionEVT 201 improved PSG measures of sleep onset and sleep maintenance and significantly reduced daytime physiological sleep tendency. These findings suggest that treatment of primary insomnia in older patients has the potential to improve daytime sleepiness as well as sleep.     

Predictors and patterns of insomnia symptoms in OSA before and after PAP therapy

ObjectiveIdentify factors that predict improvement versus persistence of insomnia symptoms following treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy.MethodsArchival data from 68 PAP-treated sleep apnea patients aged 25–83 were analyzed using nonparametric tests and stepwise regression to assess the relationships between insomnia symptoms, multiple OSA variables, and PAP use over time.ResultsPretreatment insomnia symptom severity (ISS; b = −0.72, p < 0.001), PAP average use (b = −0.01, p = 0.01) and respiratory disturbance index (RDI; b = −0.02, p = 0.03) predict change in insomnia following PAP therapy. Forty-five percent (24/53) of the subjects with moderate to severe insomnia at pretreatment reported no/mild symptoms after PAP therapy and were considered improved. Improved subjects had lower pretreatment ISS (p < 0.001), higher RDI (p = 0.01), and higher average PAP use (p < 0.035) than subjects with persistent insomnia. Number of medications and comorbidities were similar between improved and persistent groups. New onset of insomnia symptoms occurred in 13% (2/15) of the patients with no/mild pretreatment insomnia.ConclusionsAlthough ISS declines following PAP treatment, 55% of OSA patients have persistent moderate to severe symptoms despite treatment. More severe OSA is linked to higher likelihood of insomnia improvement and the effect of PAP therapy on insomnia may be mediated by OSA severity. Persistent insomnia is unrelated to medication use or comorbidities and may represent an independent, self-sustaining disorder requiring targeted intervention.     

Belgian Schizophrenia Outcome Survey – Results of a 2-year naturalistic study in patients stabilised on monotherapy with olanzapine,risperidone or haloperidol

ObjectivesThis Schizophrenia Outcome Survey compared medical costs, psychopathology and adverse events in outpatients for 2 years following hospitalisation for an acute schizophrenic episode.MethodsAdults stabilised with haloperidol, olanzapine or risperidone entered this observational study ≤1 month after discharge and were assessed at baseline, 3, 6, 12, 18 and 24 months using Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), Global Assessment of Functioning and adverse events reporting.ResultsAmong 323 patients (haloperidol 32, olanzapine 149, risperidone 142), baseline characteristics were similar in the olanzapine and risperidone groups, except for more first episodes in the risperidone group (p = 0.01). Haloperidol patients were more often single and institutionalised, less educated, had more residual schizophrenia, were longer hospitalised in the previous year, took more corrective and psychotropic drugs and had more extrapyramidal symptoms (EPS) and gynaecomastia (all significantly). Sixty-eight percent of patients completed a 2-year follow-up. In all groups, CGI and GAF improved during the first 3 months (both p < 0.0001) while BPRS deteriorated in the first year (all within group changes p < 0.05, between group changes NS) before it stabilised. There were no significant differences in hospitalisations and no change in social profile. At the last visit, 66% of haloperidol (p < 0.01), 35% of olanzapine (NS) and 39% (NS) of risperidone patients had ≥1 EPS; 69% (p < 0.013), 40 and 44%, respectively, had ≥1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p < 0.05) and 2.6 kg (p < 0.05), respectively.ConclusionsIn this naturalistic study, treatment allocation might have introduced a bias in the interpretation of efficiency results, but olanzapine and risperidone caused less EPS than haloperidol during 2 years of outpatient follow-up.     

Does CPAP treatment in mild obstructive sleep apnea affect blood pressure?

ObjectivesObstructive sleep apnea (OSA) is associated with significant cardiovascular (CV) morbidity. Continuous positive airway pressure (CPAP) is the standard treatment for moderate to severe OSA, resulting in a reduction in CV morbidity. No studies have compared CV outcomes between CPAP and no CPAP in mild OSA (5 ? AHI < 15).MethodsRetrospective cohort study of subjects (age ? 18) with mild OSA diagnosed between 2004 and 2006. Subjects with a history of hypertension, angina, stroke and smoking were excluded. Subjects were stratified into two groups: CPAP (n = 93) or no CPAP (n = 162). The mean blood pressures (MBP) were compared 2 years after the diagnosis of OSA was established.ResultsUnmatched for covariates (age, sex, BMI, neck circumference, AHI, arousal index and family h/o CV disorders), subjects with mild OSA on CPAP had a 1.97 point reduction, and no CPAP resulted in a 9.61 point elevation (p < 0.0001) in MBP. With propensity score matching for covariates, the mean difference in MBP was ?1.97 (95% CI: ?14.03, ?9.92; p < 0.0001) with a sensitivity analysis of 2.646.ConclusionThis study shows an elevation of the MBP in mild OSA patients who were not treated with CPAP. CPAP treatment in mild OSA patients decreased the MBP over a 2-year period.