Cardiac-related findings at autopsy in people with severe mental illness treated with clozapine or risperidone

Clozapine is a superior agent for treatment-refractory patients with schizophrenia, but is underutilized in the US, likely due to the risk of side effects. This study examined all available autopsy data on cardiac disease and risk factors in people with schizophrenia in a sample of deceased persons with severe mental illness who had received clozapine (N = 62) or risperidone (N = 42). The mean body mass index (BMI) at the time of death was 31.4 ± 8.8 kg/m² and 27.1 ± 8.2 kg/m² in the clozapine and risperidone groups respectively (t = 1.98, df = 60, p = 0.052). Cardiac related measures examined included: abdominal wall thickness, heart weight, left ventricle thickness, right ventricle thickness, presence of notable cardiac involvement (atherosclerosis, fibrosis and hypertrophy) and number of cardiac arteries occluded. No significant differences in any of the cardiac findings were noted between patients in the clozapine and risperidone groups. Independent of treatment, cardiomyopathy deaths were associated with a higher abdominal wall thickness (p = 0.042) and a tendency towards higher BMI (p = 0.051) as compared to the other causes of death. The results of this study suggest that while clozapine is associated with weight gain and metabolic abnormalities, there does not appear to be an increased occurrence of cardiac abnormalities in deceased persons who were treated with clozapine as compared to risperidone.     

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.     

Minimally invasive transforaminal lumbar interbody fusion for spondylolisthesis in patients with significant obesity

Comparative studies evaluating efficacy and safety of minimally invasive spinal fusion between patients with significant obesity (body mass index [BMI] ? 35 kg/m²) and those of normal weight are scarce. We examined complication rates and outcomes for minimally invasive transforaminal lumbar interbody fusion (MITLIF) in patients with significant obesity and those of normal weight undergoing treatment for symptomatic spondylolisthesis. Patients with a BMI ? 35 kg/m² or <25 kg/m² undergoing elective MITLIF for symptomatic spondylolisthesis for the period 2006–09 were identified. Of the 16 patients identified, nine patients with a mean BMI of 37.4 kg/m² were included in the obese group, while seven patients with a mean BMI of 23.4 kg/m² comprised the normal weight group. Estimated blood loss (EBL), operative time, complication rate, length of hospital stay, and clinical outcomes were assessed. Outcome measures included patient-reported visual analog scale (VAS) score for pain and the Oswestry Disability Index (ODI) questionnaire completed by the patient. No significant differences were found in blood loss (p = 0.436), hospital stay (p = 0.606), or number of surgical complications (p = 0.920) between the two groups. Mean follow-up intervals were 15.0 months for patients with obesity, and 18.6 months for those of normal weight. Both groups had significant improvements in VAS (obese, p = 0.003; normal, p = 0.016) and ODI (obese, p = 0.020; normal, p = 0.034) scores. There were no statistically significant differences between normal weight and obese groups in postoperative VAS (p = 0.728) and ODI (p = 0.886) scores. Patients with significant obesity experienced clinical improvement similar to that of patients with normal weight, suggesting that obesity does not impact MITLIF outcomes. In addition, both groups experienced similar complication rates, operative times, EBL, and length of hospital stay.     

Prevalence of residual excessive sleepiness during effective oral appliance therapy for sleep-disordered breathing

BackgroundOral appliance therapy with a mandibular advancement device (OA_m) can yield to complete therapeutic response (apnea–hypopnea index [AHI] < 5 events/h), though some patients show little or no improvement in daytime sleepiness. The prevalence of residual excessive sleepiness (RES) despite effective treatment with OA_m therapy is unknown. We aimed to determine the prevalence of RES in patients treated with a titratable custom-made duobloc OA_m.MethodsA prevalence study was performed, collecting data from 185 patients with an established diagnosis of sleep-disordered breathing (SDB) under OA_m therapy with a titratable custom-made duobloc device (baseline data were male:female ratio, 129:56; age, 48 ± 9 years; body mass index [BMI], 27 ± 4 kg/m²; Epworth Sleepiness Scale [ESS] score, 10 ± 5; and AHI, 19 ± 12 events/h). A full-night polysomnography was performed at baseline and after 3 months of OA_m therapy. Daytime sleepiness was assessed using the ESS with RES defined as an ESS score of 11 or higher out of 24, despite complete therapeutic response.ResultsOut of 185 patients, 84 patients (45%) showed a complete therapeutic response with an AHI of <5 events per hour after 3 months of OA_m therapy. Despite this normalization of AHI, 27 out of these 84 patients (32%) showed RES and had a significantly higher baseline ESS (15 ± 4 vs 9 ± 4; P < .001) and were younger (43 ± 9 vs 47 ± 9; P = .028) compared to patients without RES.ConclusionRES under OA_m therapy showed a prevalence of up to 32% in SDB patients effectively treated with respect to AHI. Patients with RES were younger and had higher baseline daytime sleepiness.     

Nocturnal eating is part of the clinical spectrum of restless legs syndrome and an underestimated risk factor for increased body mass index

ObjectivesWe aimed to investigate the prevalence of night eating syndrome (NES) in a large cohort of patients with restless legs syndrome (RLS).MethodsOur cross-sectional study included 120 patients examined at the University of Bologna Centre for Sleep Disorders, Bologna, Italy, and met all four International RLS criteria for the diagnosis of RLS. Each patient underwent a semistructured telephone interview investigating demographic data and general health status, RLS features and severity, presence of excessive daytime sleepiness, and presence of NES.ResultsThe sample included 37 men and 83 women with a mean age of 63.8 ± 11.5 years. There were 31% of patients who reported episodes of nocturnal eating (NE); among them, 17% fulfilled the new diagnostic criteria for NES. Comparing RLS patients with and without NE, there were no differences in RLS features. However, RLS patients with NE were older (67.2 ± 11.6 vs 62.4 ± 11; P = .038), were in a higher body mass index (BMI) range (27.7 ± 3.8 vs 26.1 ± 4.1 kg/m²; P = .023), were taking more drugs for concomitant diseases (89% vs 72%; P = .031), were more likely to report insomnia (40% vs 23%; P = .041), and were using more hypnotic agents (37.8% vs 19.3%; P = .050) and dopaminergic drugs (65% vs 46%; P = .041). When comparing those RLS patients with NES diagnostic criteria and those without NES, no differences emerged in demographic, clinical, and RLS features; however, NES patients were in a higher BMI range (28.3 ± 4.1 vs 26.2 ± 3.9 kg/m², P = .037), were more frequently smokers (43% vs 17%; P = .027), and were more frequently using hypnotic agents (30% vs 24%; P = .025). Lastly, no differences were found when comparing patients with a NES diagnosis and those with NE not fitting the diagnostic criteria for NES, except for a higher use of benzodiazepine drugs (BDZ) in this latter subgroup (29% vs zero; P = .014).ConclusionsA nocturnal compulsion to eat seems to be an intrinsic part of the clinical spectrum of RLS manifestations and an odd risk factor for increases in BMI in RLS patients. However, it is still not clear if NE in RLS would fit in one of the two known categorized syndromes of NE (i.e., sleep-related eating disorder [SRED] or NES) or if it represents a different strictly RLS-related eating behavior.     

Risk factor analysis for meralgia paresthetica: A hospital-based study in Taiwan

Recognizing the cause is essential for the management of meralgia paresthetica (MP), also known as lateral femoral cutaneous neuropathy. The aim of this study was to investigate the etiologies of MP and their influence on each other. This retrospective study enrolled referral patients with electromyographic studies who fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to December 2013. Data including age, gender, body weight, body height, occupation, and relevant medical history were collected. The etiological analysis was based on age and gender. A total of 50 patients (30 males and 20 females) were enrolled. The average age (±standard deviation) at diagnosis was 49.8 ± 12.8 years. Risk factors were identified in 29 cases (58.0%). More patients younger than 50 years of age were male (73.1%, p = 0.049). Peaks of age occurred between 41–50 years in men and 51–60 years in women. More males had a body mass index ≥ 24 kg/m² (69.2% vs. 31.6%, p = 0.012) and ≥27 kg/m² (34.6% vs. 0.0%, p = 0.006). Overweight and obese patients were more vulnerable to occupational factors (50.0% vs. 19.0%, p = 0.030). Only one case had diabetes mellitus (2%). Male middle-aged patients with a higher body mass index and certain occupations had an increased risk of MP. In contrast to the peak age distribution of the male patients, the frequency of developing MP was relatively even among the women at all ages. The cause was often obscure.     

Adiposity is increased among high-functioning,non-ambulatory patients with spinal muscular atrophy

The relationship between body composition and function in spinal muscular atrophy (SMA) is poorly understood. 53 subjects with SMA were stratified by type and Hammersmith functional motor scale, expanded score into three cohorts: low-functioning non-ambulatory (type 2 with Hammersmith score <12, n = 19), high-functioning non-ambulatory (type 2 with Hammersmith score ⩾ 12 or non-ambulatory type 3, n = 17), and Ambulatory (n = 17). Lean and fat mass was estimated using dual-energy X-ray absorptiometry. Anthropometric data was incorporated to measure fat-free (lean mass in kg/stature in m²) and fat (fat mass in kg/stature in m²) mass indices, the latter compared to published age and sex norms. Feeding dysfunction among type 2 subjects was assessed by questionnaire. Fat mass index was increased in the high-functioning non-ambulatory cohort (10.4 ± 4.5) compared with both the ambulatory (7.2 ± 2.1, P = 0.013) and low-functioning non-ambulatory (7.6 ± 3.1, P = 0.040) cohorts. 12 of 17 subjects (71%) in the high-functioning non-ambulatory cohort had fat mass index >85th percentile for age and gender (connoting “at risk of overweight”) versus 9 of 19 subjects (47%) in the low-functioning non-ambulatory cohort and 8 of 17 ambulatory subjects (47%). Despite differences in clinical function, a similar proportion of low functioning (7/18, 39%) and high functioning (2/7, 29%) type 2 subjects reported swallowing or feeding dysfunction. Non-ambulatory patients with relatively high clinical function may be at particular risk of excess adiposity, perhaps reflecting access to excess calories despite relative immobility, emphasizing the importance of individualized nutritional management in SMA.     

The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

BackgroundPersistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder.MethodsEuthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5–24.9 kg/m²; overweight/obese, BMI ≥ 25.0 kg/m²). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures.ResultsBMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task).ConclusionNotwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations.     

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

BackgroundThe angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity.MethodsMale OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping.ResultsWe studied 266 males with OSA (age = 48 ± 13y, body mass index = 29 ± 5kg/m², AHI = 34 ± 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and II genotype (OR = 0.27).ConclusionsOur results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA.     

Sleep and cardiometabolic function in obese adolescent girls with polycystic ovary syndrome

ObjectiveTo compare the polysomnography findings and cardiometabolic function among adolescent girls with polycystic ovary syndrome (PCOS) and matched female and male controls.MethodRetrospective chart review of electronic medical records of 28 girls with PCOS (age: 16.8 ± 1.9 years, body mass index (BMI) Z-score 2.4 ± 0.4), 28 control females (age: 17.1 ± 1.8, BMI Z-score 2.4 ± 0.3) and 28 control males (age: 16.6 ± 1.6, BMI Z-score 2.5 ± 0.5) in a tertiary care centre.ResultsThe prevalence of obstructive sleep apnoea (OSA) was higher in girls with PCOS compared to control females (16/28 (57%) vs. 4/28(14.3%), p < 0.01); however, it was comparable to that of the control males (16/28(57%) vs. 21/28(75%), p = 0.4). Girls with PCOS had a significantly higher prevalence of insulin resistance compared to control females and control males (20/28 (71.4%) vs. 9/22 (41.0%) (p = 0.04) vs. 8/23 (34.8%) (p = 0.01). Among girls with PCOS, those with OSA had significantly higher proportions of metabolic syndrome (MetS) (9/16 (56.3%) vs. 1/12 (8.3%) p = 0.03), higher insulin resistance (14/16 (87.5%) vs. 6/12 (50%), p = 0.04), elevated daytime systolic blood pressure (128.4 ± 12.8 vs. 115.6 ± 11.4, p < 0.01), lower high-density lipoprotein (HDL) (38.6 ± 8.7 vs. 49 ± 10.9, p = 0.01) and elevated triglycerides (TG) (149.7 ± 87.7 vs. 93.3 ± 25.8, p = 0.03) compared to those without OSA.ConclusionsWe report a higher prevalence of OSA and metabolic dysfunction in a selected group of obese girls with PCOS referred with sleep-related complaints compared to BMI-matched control girls without PCOS. We also report higher prevalence of cardiometabolic dysfunction in girls with PCOS and OSA compared to girls with PCOS without OSA.     

Sleep duration and obesity in a population-based study

BackgroundPrevious studies have demonstrated an association between sleep duration and obesity, but few population-based studies have examined the association. We examined the relationship between recent and usual lifetime sleep duration with the odds of obesity in 5549 women that participated in a population-based telephone survey.MethodsThe structured telephone interview included questions on usual sleep duration in adult life and the recent past, as well as height and weight and other demographic and lifestyle characteristics. We examined odds of overweight (BMI: 25–29.9 kg/m²), obesity (BMI: 30–39.9 kg/m²) and extreme obesity (BMI: ?40 kg/m²) according to reported sleep duration.ResultsCompared to women who slept 7–7.9 h per night, women who slept an average of <6 h per night in the recent past had significantly greater odds of obesity (Odds Ratio [OR]: 1.89; 95% Confidence Interval [CI]: 1.45–2.47) and extreme obesity (OR: 3.12; CI: 1.70–5.75), adjusting for potential confounding factors. Weaker associations were noted for short lifetime sleep duration. Current short sleep (<7 h) was associated with greater odds of obesity (?30 kg/m²) in those reporting less than 7 h (OR: 1.59; 95% CI: 0.93–2.78) and in those reporting 8 or more hours (OR: 1.75; 95% CI: 1.33–2.32) of sleep throughout adult life.ConclusionsCurrent short sleepers were more likely to be obese regardless of their usual sleep duration earlier in life. These findings do not support the hypothesis that sleep duration is a causal factor in obesity.     

Eurofit test battery in patients with schizophrenia or schizoaffective disorder: Reliability and clinical correlates

ObjectiveTo investigate the reproducibility of the Eurofit physical fitness test battery in patients with schizophrenia or schizoaffective disorder. Secondary aims were to assess clinical and demographic characteristics that correlate with the performance on the Eurofit and evaluation of the feasibility of the test.MethodsFifty patients with schizophrenia or schizoaffective disorder (mean age of 32.9 ± 9.5 years) with a mean body mass index (BMI) of 26.1 ± 6.0 kg/m² performed two Eurofit tests administered within 3 days.ResultsAll Eurofit items showed good reproducibility with intraclass correlation coefficients ranging from 0.72 for flamingo balance to 0.98 for standing broad jump test. All participants could perform five of the seven test items without problems. The whole body balance and abdominal muscle endurance test could be executed by 74 and 90%, respectively. Significant correlations were found with age, BMI, waist circumference, dose of antipsychotic medication and extrapyramidal, negative and cognitive symptoms.ConclusionsThe Eurofit test showed good reproducibility and can be recommended for evaluating physical fitness parameters in patients with schizophrenia or schizoaffective disorder. Physical fitness measures were related to both physical and mental health parameters.     

Association between sleep duration,weight gain,and obesity for long period

BackgroundAlthough previous studies showed the long-term effects of sleep duration on risk of weight gain, Western tends to gain weight irrespective of sleep duration over a long period. Conversely, it is showed that body mass index (BMI) decreases during a long period in Japanese and thus, the long-term effect of sleep duration on weight gain and obesity is still unclear in Asia.MethodsWe followed up 13,629 participants aged 40–79 years and prospectively collected data from 1995 to 2006. We divided the participants into five groups according to their self-reported sleep duration: ⩽5 h (short sleep), 6 h, 7 h (reference), 8 h, and ⩾9 h (long sleep). The main outcome was ⩾5 kg weight gain or BMI ⩾ 25 kg/m² (obesity). We used logistic regression analyses to derive odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for several confounding factors.ResultsWe observed no association between sleep duration and risk of ⩾5 kg weight gain and obesity. After stratification by BMI, long sleepers had a significantly increased risk of ⩾5 kg weight gain (OR: 1.36, 95%CI: 1.09–1.70) in obese participants.ConclusionsAmong community-dwelling Japanese, only obese long sleepers have a significantly increased long-term risk of ⩾5 kg weight gain.     

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.     

Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure

This study evaluated efficacy and safety of growth hormone treatment in Duchenne muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed 39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth hormone for 1 year during a four-year period. Boys were on long-term daily deflazacort or prednisone (mean duration 5 ± 2.2 years; dosing regimen prednisone 0.75 mg/kg/day equivalent). Primary outcomes were growth velocity and height-for-age z-scores (height SD) at 1 year. Height velocity increased from 1.3 ± 0.2 to 5.2 ± 0.4 cm/year on growth hormone (p < 0.0001). Pre-growth hormone decline in height SD (−0.5 ± 0.2 SD/year) stabilized at height SD −2.9 ± 0.2 on growth hormone (p < 0.0001). The rate of weight gain was unchanged, at 2.8 ± 0.6 kg/year pre-growth hormone and 2.6 ± 0.7 kg/year at 1 year. Motor function decline was similar pre-growth hormone and at 1 year. Cardiopulmonary function was unchanged. Three experienced side effects. In this first comprehensive report of growth hormone in Duchenne muscular dystrophy, growth hormone improved growth at 1 year, without detrimental effects observed on neuromuscular and cardiopulmonary function.     

Inhibitory effect of dimethylthiourea on rat urinary bladder inflammation produced by 6-hydroxydopamine application

The present study was to investigate 6-hydroxydopamine (6-OHDA)-induced inflammatory response and underlying mechanisms in the urinary bladder in anesthetized male rats of Long–Evans strain. The magnitude of inflammation was evaluated by morphometric analysis of the relative number of leaky blood vessels expressed by the area density of India ink-labeled blood vessels in whole mount specimens. Light and scanning electron microscopies were employed to study the changes in histologic structure and endothelial ultrastructure of bladder wall. Local injection of 6-OHDA to lumen of urinary bladder induced a dose-dependent increase in plasma leakage. Following application of vehicle, 5 mg/kg 6-OHDA, and 10 mg/kg 6-OHDA, area densities of India ink-labeled leaky vessels were 5.65 ± 3.72% (N = 6), 22.63 ± 5.12% (N = 6), and 35.02 ± 11.25% (N = 6), respectively. Inflammatory response was completely abolished by pretreatment alone with dimethylthiourea (DMTU), a hydroxyl radical scavenger, and was also attenuated by pretreatment with L-732,138, a NK1 receptor antagonist. 6-OHDA caused edema formation and venular endothelial gap formation in bladder tissue. It is concluded that 6-OHDA induced inflammation in the rat urinary bladder, the response of which was dose-dependently increased and free radicals and tachykinins were involved in the inflammatory process.     

Chronic valproate or levetiracetam treatment does not influence cytokine levels in humans

PurposeThere is growing evidence that complex interactions between seizures and the immune system shape the course of epilepsy. However, systematic analyses of the effects of antiepileptic drugs (AED) on the immune system in humans are rare. We performed a prospective study on the influence of the widely used AED valproate and levetiracetam on interictal immunological parameters.Methods36 patients were prospectively included. 15 were started on valproate (5 female (33%), age 54 ± 27 years, 12 (80%) on monotherapy), 21 on levetiracetam (10 female (48%), age 45 ± 19 years, 17 (81%) on monotherapy). Before treatment and after 3 months, we performed a differential blood count and analyzed the distribution of CD3⁺CD4⁺-, CD3⁺CD8⁺- and CD4⁺CD25⁺-leukocyte subsets using flow cytometry. In addition, we determined the concentrations of IL-1β, IL-6, TNF-α and MCP-1 in the peripheral blood using ELISAs.ResultsValproate intake resulted in a significant decrease of the total white blood count (6.96 ± 1.23/nl vs. 6.13 ± 1.57/nl, p = 0.026) and of absolute count and percentage of neutrophils (4.60 ± 1.05/nl vs. 3.69 ± 1.30/nl, p = 0.01; 65.4 ± 7.9% vs. 59.5 ± 11.5%, p = 0.01, respectively). The percentage of CD3⁺CD4⁺-lymphocytes dropped significantly (50.4 ± 10.9% vs. 45.3 ± 12.3%, p = 0.002). Levetiracetam treatment resulted in a decrease of the percentage of CD4⁺CD25⁺-lymphocytes (26.1 ± 8.0% vs. 21.5 ± 9.2%, p = 0.01) but did not significantly alter absolute counts. Neither valproate nor levetiracetam were associated with significant changes in cytokines.ConclusionValproate intake results in profound changes of white blood cell count and subset distribution. Cytokine levels were not influenced by valproate or levetiracetam.     

Risperidone or aripiprazole in children and adolescents with autism and/or intellectual disability: A Bayesian meta-analysis of efficacy and secondary effects

Second-generation antipsychotics (SGAs) induce frequent adverse effects in children and adolescents with each compound appearing to have a specific adverse effect profile. Aripiprazole and risperidone are FDA-approved medications for behavioral disturbances associated with autism and/or intellectual disabilities (ID) in children and adolescents. Using Bayesian meta-analysis of all relevant studies (N = 8; 18 arms; 782 patients), we aimed to calculate odds ratios (OR) or mean average effects to assess efficacy, weight gain, metabolic changes, sedation, and extra-pyramidal syndrome (EPS) of the two compounds. Reporting was incomplete to assess metabolic changes. Compared to placebo, significant treatment-related increases were observed for: CGI response with aripiprazole (OR = 6.09, 95% credible interval [2.3–12.63]) and risperidone (12.8 [5.57–27.33]); weight gain with aripiprazole (OR = 6.28 [1.64–17.12]) and risperidone (7.76 [1.88–25.2]); EPS with risperidone (OR = 3.72 [1.73–7.22]); and somnolence/sedation with aripiprazole (OR = 25.76 [1.29–112.3]) and risperidone (9.63 [3.52–22.79]). There were no significant differences between active compounds. We conclude that short term efficacy of risperidone and aripiprazole are similar for behavioral disturbances associated with autism and/or ID, and that secondary effects are frequent. More research should be conducted on metabolic changes as current literature is lacking compared to other indications in youths.     

The impact of obstructive sleep apnea and daytime sleepiness on work limitation

BackgroundMany patients with obstructive sleep apnea (OSA) participate in the work force. However, the impact of OSA and sleepiness on work performance is unclear.MethodsTo address this issue, we administered the Epworth Sleepiness Scale (ESS), the Work Limitations Questionnaire (WLQ), and an occupational survey to patients undergoing full-night polysomnography for the investigation of sleep-disordered breathing. Of 498 patients enrolled in the study, 428 (86.0%) completed the questionnaires. Their mean age ± standard deviation (SD) was 49 ± 12years, mean body mass index (BMI) was 31 ± 7 kg/m² mean apnea hypopnea index (AHI) was 21 ± 22 events/h, and mean ESS score was 10 ± 5. Subjects worked a mean of 39 ± 18 h per week. The first 100 patients to complete the survey were followed up at two years.ResultsIn the group as a whole, there was no significant relationship between severity of OSA and the four dimensions of work limitation. However, in blue-collar workers, significant differences were detected between patients with mild OSA (AHI 5–15/h) and those with severe OSA (AHI > 30/h) with respect to time management (limited 23.1% of the time vs. 43.8%, p = 0.05) and mental/personnel interactions (17.9% vs. 33.0%, p = 0.05). In contrast, there were strong associations between subjective sleepiness (as assessed by the ESS) and three of the four scales of work limitation. That is, patients with an ESS of ⩽5 had much less work limitation compared to those with an ESS ⩾18 in terms of time management (19.7% vs. 38.6 %, p < 0.001), mental-interpersonal relationships (15.5% vs. 36.0%, p < 0.001) and work output (16.8% vs. 36.0%; p < 0.001). Of the group followed up, 49 returned surveys and 33 who were using continuous positive airway pressure (CPAP) showed significant improvements between the initial and second follow-up in time management (26% vs. 9%, p = 0.0005), mental-interpersonal relationships (16% vs. 11.0%, p = 0.014) and work output (18% vs. 10%; p < 0.009).ConclusionWe have demonstrated a clear relationship between excessive sleepiness and decreased work productivity in a population referred for suspected sleep-disordered breathing. Screening for sleepiness and sleep-disordered breathing in the workplace has the potential to identify a reversible cause of low work productivity.     

Pulmonary capillary wedge pressure and pulmonary arterial pressure in heart failure patients with sleep-disordered breathing

BackgroundThere is a high prevalence of central sleep apnea (CSA) in patients with chronic heart failure (CHF). The present study investigates the hypotheses that CSA in CHF patients reflects heart failure severity as measured by cardiac index (CI), pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP).MethodsIn 105 patients with stable CHF (NYHA ? II, LV-EF ? 40%) cardiorespiratory polygraphy and simultaneous right and left heart catheterization was performed.ResultsCSA was present in 58% and obstructive sleep apnea (OSA) in 23% of patients. In CSA patients, PAP and PCWP were significantly higher when compared to patients without SDB. In CSA patients, but not in OSA patients, PCWP showed a significant correlation with apnea–hypopnea index (AHI; r = 0.41, p = 0.005), apnea index (AI; r = 0.44, p = 0.003) and central AI (cAI; r = 0.358, p = 0.015). Cardiac index was more impaired in CSA (1.93 ± 0.5 l/min/m²) than in OSA patients (2.55 ± 1.0 l/min/m²) or those without SDB (2.22 ± 0.4 l/min/m²). A negative correlation of CI and cAI (r = ?0.344, p = 0.008), AI (r = ?0.31, p = 0.02) and AHI (r = ?0.21, p < 0.05) was documented exclusively in CSA patients.ConclusionThe present study supports the hypotheses that the occurrence and severity of CSA in CHF patients reflects heart failure severity.