Extended-release divalproex in bipolar and other psychiatric disorders: A comprehensive review

Bipolar disorder can be a devastating disease state for individuals with the disease and also for family members. Proper recognition and treatment is vital to the successful management of this disease state. Through increased community and practitioner awareness, along with efforts to increase awareness for proper assessment, the rate of diagnosed bipolar disorder is increasing. Recent years have brought about the introduction of several new medications with approved indications for the treatment of bipolar disorder. In addition to new agents, traditional mood stabilizing medications have also been released in different formulations to better enhance tolerability without jeopardizing efficacy. One particular product is extended-release divalproex sodium. In the following article, we review the clinical presentation of bipolar disorder, its epidemiology, and the pharmacokinetics and mechanism of action for divalproex. In addition, we specifically review the role of extended-release divalproex in bipolar disorder through a critical analysis of the currently available published primary literature.     

Predictors of oral health quality of life in older adults

There is limited information regarding oral health status and other predictors of oral health‐related quality of life. An association between oral health status and perceived oral health‐related quality of life (OHQOL) might help clinicians motivate patients to prevent oral diseases and improve the outcome of some dental public health programs. This study evaluated the relationship between older persons' OHQOL and their functional dentition, caries, periodontal status, chronic diseases, and some demographic characteristics. A group of 733 low‐income elders (mean age 72.7 ISD=4.71, 55.6% women, 55.1% members of ethnic minority groups in the U.S. and Canada) enrolled in the TEETH clinical trial were interviewed and examined as part of their fifth annual visit for the trial. OHQOL was measured by the Geriatric Oral Health Assessment Index (GOHAI); oral health and occlusal status by clinical exams and the Eichner Index; and demographics via interviews. Elders who completed the four‐year assessment had an average of 21.5 teeth (SD=6.9). with 8.5 occluding pairs (SD=4.6), and 32% with occlusal contacts in all four occluding zones. Stepwise multiple regressions were conducted to predict total GOHAI and its subscores (Physical, Social, and Worry). Functional dentition was a less significant predictor than ethnicity and being foreign‐bom. These variables, together with gender, years since immigrating, number of carious roots, and periodontal status, could predict 32% of the variance in total GOHAI, 24% in Physical, 27% in Social, and 21 % in the Worry subscales. These findings suggest that functional dentition and caries influence older adults' OHQOL, but that ethnicity and immigrant status play a larger role.     

Changes in sleep polygraphic variables and clinical state in depressed patients during treatment with citalopram

Drug-induced improvement of depression may be mediated by changes in sleep physiology. The aim of this study was to relate changes in sleep polygraphic variables to clinical state during treatment with citalopram, a highly specific serotonin uptake inhibitor. Sixteen patients took part. The study was single-blind and uncontrolled. A 1-week wash-out period was followed by 1 week of placebo administration, a medication period of 5 weeks, and a 1-week placebo period. For the entire group a significant decrease of rapid eye movement sleep (REMS) and a significant lengthening of REMS latency were observed initially as well as at the end of treatment. No changes in sleep continuity were found, but non-REMS stage 2 (percentage) was significantly increased. On the basis of clinical change, as expressed by the scores of the Hamilton Rating Scale for Depression, at the end of the citalopram treatment the patient group was split in two halves: eight less and eight more improved patients. The groups did not differ with respect to any sleep polygraphic varible.     

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Sleep in seasonal affective disorder patients in forced desynchrony: an explorative study

The majority of winter-type seasonal affective disorder (SAD) patients complain of hypersomnia and daytime drowsiness. As human sleep is regulated by the interaction of circadian, ultradian and homeostatic processes, sleep disturbances may be caused by either one of these factors. The present study focuses on homeostatic and ultradian aspects of sleep regulation in SAD. Sleep was recorded polysomnographically in seven SAD patients and matched controls subjected to a 120-h forced desynchrony protocol. In time isolation, subjects were exposed to six 20-h days, each comprising a 6.5-h period for sleep. Patients participated while being depressed, while remitted after light therapy and in summer. Controls were studied in winter and in summer. In each condition, the data of each subject were averaged across all recordings. Thus, the influence of the effects of the circadian pacemaker on sleep was excluded mathematically. The comparison of patients with controls and with themselves in the various conditions revealed no abnormalities in homeostatic parameters: sleep stage variables, relative power spectra and time courses of power in various frequency bands across the first three non-rapid eye movement-rapid eye movement (NREM-REM) cycles showed no differences. The data suggest that homeostatic processes are not involved in the disturbance of sleep in SAD.     

The reliability and validity of the Seasonal Pattern Assessment Questionnaire: a comparison between patient groups

Background: The Seasonal Pattern Assessment Questionnaire (SPAQ) is a frequently used screening instrument in the research on Seasonal Affective Disorder (SAD). Nevertheless, studies on its reliability and validity are relatively scarce. In the present study the reliability and the contrast validity of the SPAQ are investigated. Methods: SAD patients, selected by means of a clinical interview, non-seasonal depressed out-patients, non-depressed out-patients, and a control group, are contrasted to estimate the discriminating power of the SPAQ. Also, the reliability and factor structure of the seasonality and the climate subscales are investigated. To study food intake the Seasonal Food Preference Questionnaire (SFPQ) was developed. Results: The SAD criterion of the SPAQ shows good specificity (94%), but a low sensitivity (44%). Discriminant analysis shows sufficient ability to classify subjects (81% correctly classified). The Global Seasonality Scale has a good internal consistency. It consists of two factors, a psychological factor and a food factor. The SFPQ is sensitive for carbohydrate intake by SAD patients. Limitations: Most SAD patients had received treatment and completed the SPAQ while they were not depressed, which may have influenced the sensitivity. Conclusions: The SPAQ is not sensitive enough to be considered a diagnostic instrument for SAD. Nevertheless, it is accurate enough to be used as a screenings instrument. The only false positives were found in the depressive group. The accuracy of prevalence Figs. can be improved by completion of the SPAQ in the summer months, combined with the completion of a depression scale.     

Hypothermic Machine Preservation in Liver Transplantation Revisited: Concepts and Criteria in the New Millennium

To overcome the present shortage of liver donors by expansion of the existing donor pool and possibly lengthening of the storage time, hypothermic machine perfusion of the liver as a dynamic preservation method is revisited. The three most important aspects are defined to be the type of preservation solution, the characteristics of perfusion dynamics, and the oxygen supply. Reviewing hypothermic liver machine perfusion experiments, the University of Wisconsin machine preservation solution is the solution most used. It is also found that nothing conclusive can be said about the optimal perfusion characteristics, since either perfusion pressure or perfusion flow is reported. The best estimation is perfusion of the liver in a physiological manner, i.e. pulsatile arterial perfusion and continuous portal venous perfusion. The applied pressures could be chosen to be somewhat lower than physiological pressures to prevent possible endothelial cell damage. Oxygen supply is necessary to achieve optimal preservation of the liver. The minimal amount of partial oxygen pressure required is inversely related to the normalized flow. Incorporating these features in a system based on existing standard surgical and organ sharing procedures and which is able to work stand-alone for 24 h, weighing less than 23 kg, could successfully implement this technique into every day clinical practise.     

All night spectral analysis of EEG sleep in young adult and middle-aged male subjects

The sleep EEGs of 9 young adult males (age 20–28 years) and 8 middle-aged males (42–56 years) were analyzed by visual scoring and spectral analysis. In the middle-aged subjects power density in the delta, theta and sigma frequencies were attenuated as compared to the young subjects. In both age groups power density in the delta and theta frequencies declined from NREM period 1 to 3. In the sigma frequencies, however, no systematic changes in power density were observed over the sleep episode. In both age groups the decay of EEG power (0.75–7.0 Hz) over successive NREM-REM cycles and the time course of EEG power during NREM sleep was analyzed. The decay rate of both EEG power density over successive NREM-REM cycles and EEG power density during NREM sleep was smaller in the middle-aged subjects than in the young subjects. It is concluded that the age-related differences in human sleep EEG power spectra are not identical to the changes in EEG power spectra observed in the course of the sleep episode. Therefore age-related differences in EEG power spectra cannot be completely explained by assuming a reduced need for sleep in older subjects. The smaller decay rate of EEG power during NREM sleep in the middle-aged subjects is interpreted as a reduced sleep efficiency. The results are discussed in the frame work of the two-process model of sleep regulation.     

SOST expression is restricted to the great arteries during embryonic and neonatal cardiovascular development.

Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity is essential for normal cardiovascular development, and altered activity of these growth factors causes maldevelopment of the cardiac outflow tract and great arteries. In the present study, we show that SOST, a Dan family member reported to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of the great arteries containing smooth muscle cells. The ascending aorta, aortic arch, brachiocephalic artery, common carotids, and pulmonary trunk were all associated with SOST expressing smooth muscle cells, while the heart itself, including the valves, and more distal arteries, that is, pulmonary arteries, subclavian arteries, and descending aorta, were negative. SOST was expressed from embryonic day 15.5 up to the neonatal period. SOST expression, however, did not correspond with inhibition of Smad-dependent BMP activity or beta-catenin-dependent Wnt activity in the great arteries. Activity of both signaling pathways was already down-regulated before induction of SOST expression.     

Detection of serum antibodies to bovine norovirus in veterinarians and the general population in the Netherlands

The close genetic relationship of human and animal strains of norovirus has raised the possibility of transmission of noroviruses from animals to humans and may explain the emergence of certain norovirus strains. To assess if exposure to bovine noroviruses (NoV) might result in infection in humans, an enzyme immunoassay (EIA) was designed and validated in order to detect antibodies against bovine norovirus. This and two other EIAs were used to test sera from 210 veterinarians and 630 matched population controls for IgG and IgA antibodies to recombinant capsid protein of bovine NoV (rBoV), Norwalk virus (rNV), and Lordsdale virus (rLDV). Of 840 participants, IgG reactivity to rBoV was found in 185 (22%), to rNV in 638 (76%) and to rLDV in 760 (90%). IgG reactivity to rBoV was more common in veterinarians (58/210: 28%) than in controls (127/630: 20% [P = 0.03]). IgA reactivity to rBoV was similar in both veterinarians and controls. Cross-reactivity of IgA and IgG antibodies to rBoV and rNV was seen, but 26% of all specimens positive rBoV antibodies showed high IgG reactivity to rBoV but low reactivity to rNV, suggesting a specific response to bovine antigen. No evidence of overall cross-reactivity of antibodies to rBoV and rLDV was seen. Among veterinarians, youth spent on farm (Odds Ratio [OR] = 1.8) and membership of the bovine practitioners' society (OR = 2.7) were significantly associated with IgG seroreactivity to rBoV. These data indicate that bovine strains of NoV may infect humans though less frequently than human strains.