Episodes In Individuals Research Articles

Is blunted cardiovascular reactivity in depression mood-state dependent? A comparison of major depressive disorder remitted depression and healthy controls

Prior work has repeatedly demonstrated that people who have current major depression exhibit blunted cardiovascular reactivity to acute stressors (e.g., Salomon et al., 2009). A key question regards the psychobiological basis for these deficits, including whether such deficits are depressed mood-state dependent or whether these effects are trait-like and are observed outside of depression episodes in vulnerable individuals. To examine this issue, we assessed cardiovascular reactivity to a speech stressor task and a forehead cold pressor in 50 individuals with current major depressive disorder (MDD), 25 with remitted major depression (RMD), and 45 healthy controls. Heart rate (HR), blood pressure and impedance cardiography were assessed and analyses controlled for BMI and sex. Significant group effects were found for SBP, HR, and PEP for the speech preparation period and HR, CO, and PEP during the speech. For each of these parameters, only the MDD group exhibited attenuated reactivity as well as impaired SBP recovery. Reactivity and recovery in the RMD group more closely resembled the healthy controls. Speeches given by the MDD group were rated as less persuasive than the RMD or healthy controls' speeches. No significant differences were found for the cold pressor. Blunted cardiovascular reactivity and impaired recovery in current major depression may be mood-state dependent phenomena and may be more reflective of motivational deficits than deficits in the physiological integrity of the cardiovascular system.

Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals.

Methodology of China's national study on the evaluation, early recognition, and treatment of psychological problems in the elderly: the China Longitudinal Aging Study (CLAS).

SummaryCognitive and depressive disorders are common in elderly Chinese and are becoming an increasingly important public health problem, partly because of the rapid aging of the population. To help address this issue China's national government has funded a major study to establish national standards for the early identification, evaluation and treatment of common psychological disorders in the elderly. The present paper describes the overall methodology of this study. Fifteen centers in eight provinces will recruit representative samples of subjects aged 60 and over, collect a detailed history, conduct a physical and neurological examination, administer a comprehensive battery of psychological tests, and carry out a diagnostic exam using the Structured Clinical Interview for DSM-IV (SCID). These subjects will participate in follow-up evaluations one year and three years after the initial evaluation. Subsamples of subjects with mild cognitive impairment (MCI) and subclinical depression will be enrolled in randomized controlled trials of a cognitive training program (for MCI) or group cognitive behavioral therapy (for subclinical depression). The results of the study will be used to estimate the prevalence of cognitive and affective disorders in the elderly, to develop a standard screening procedure for these conditions that can be promulgated nationally, and to promote the use of specific interventions that can prevent the development of dementia in persons with MCI and the development of depressive episodes in elderly individuals with subclinical depression.

Translation and adaptation of the Bipolar Prodrome Symptom Scale-Retrospective: Patient Version to Brazilian portuguese.

Bipolar disorder (BD) is a chronic and often severe mental disease, associated with a significant burden in affected individuals. The characterization of a premorbid (prodromal) period and possible development of preventive interventions are recent advances in this field. Attempts to characterize high-risk stages in BD, identifying symptoms prior to the emergence of a first manic/hypomanic episode, have been limited by a lack of standardized criteria and instruments for assessment. The Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), developed by Correll and collaborators, retrospectively evaluates symptoms that occur prior to a first full mood episode in individuals with BD. To describe the translation and adaptation process of the BPSS-R to Brazilian Portuguese. Translation was conducted as follows: 1) translation of the scale from English to Brazilian Portuguese by authors who have Portuguese as their first language; 2) merging of the two versions by a committee of specialists; 3) back-translation to English by a translator who is an English native speaker; 4) correction of the new version in English by the author of the original scale; 5) finalization of the new version in Brazilian Portuguese. All the steps of the translation process were successfully accomplished, resulting in a final version of the instrument. The Brazilian Portuguese version of the BPSS-R is a potentially useful instrument to investigate prodromal period of BD in Brazil.

Association of aspirin use with major bleeding in patients with and without diabetes

Context: The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. Objective: To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. Design, setting, and participants: A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. Main outcome measures: Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. Results: There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39–5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48–3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48–1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97–1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28–1.44).

Wheezing and asthma are independent risk factors for increased sickle cell disease morbidity

To assess the associations between a doctor diagnosis of asthma and wheezing (independent of a diagnosis of asthma) with sickle cell disease (SCD) morbidity, we conducted a retrospective review of Emergency Department (ED) visits to the Mount Sinai Medical Center for SCD between 1 January 2007 and 1 January 2011. Outcomes were ED visits for pain and acute chest syndrome. The cohort included 262 individuals, median age 23·8 years, (range: 6 months to 67·5 years). At least one episode of wheezing recorded on a physical examination was present in 18·7% (49 of 262). Asthma and wheezing did not overlap completely, 53·1% of patients with wheezing did not carry a diagnosis of asthma. Wheezing was associated with a 118% increase in ED visits for pain (95% confidence interval [CI]: 56-205%) and a 158% increase in ED visits for acute chest syndrome (95% CI: 11-498%). A diagnosis of asthma was associated with a 44% increase in ED utilization for pain (95% CI: 2-104%) and no increase in ED utilization for acute chest syndrome (rate ratio 1·00, 95%CI 0·41-2·47). In conclusion, asthma and wheezing are independent risk factors for increased painful episodes in individuals with SCD. Only wheezing was associated with more acute chest syndrome.

The impact of social stress on self-esteem and paranoid ideation

BackgroundVulnerability-stress models propose that social stress triggers psychotic episodes in high risk individuals. Previous studies found not only stress but also a decrease in self-esteem to precede the formation of delusions. As evidence for causal conclusions has not been provided yet, the present study assessed the direct impact of social stress on paranoid beliefs using an experimental design and considered a decrease in self-esteem as a mediator and the proneness to psychosis and paranoia as moderators of the effect. MethodsA nonclinical population sample (n = 76) was randomly assigned to an experimental (EG) or a control group condition (CG). In the EG, participants were excluded during a virtual ball game (Cyberball) by the other two players and received a negative feedback after performing a test. The CG was included in the game and received a neutral feedback. Before and after the experimental conditions, emotions, self-esteem and paranoid beliefs were assessed using state-adapted questionnaires. ResultsAfter the social stress induction, the EG reported a higher increase in subclinical paranoid beliefs compared to the CG. The impact of social stress on paranoid ideation was mediated by a decrease in self-esteem and moderated by proneness to paranoia. Individuals who felt distressed by paranoid thoughts at baseline were more likely to react with an increase in paranoid ideation under social stress. LimitationsThe results need to be confirmed in a patient sample to draw conclusions about the processes involved in the formation of delusions in clinically relevant stages. ConclusionsThe impact of social stress on symptom formation and self-esteem is discussed in terms of recent models of symptom formation and interventions in psychosis.

Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes

The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

An Innovative Approach for Predicting Severe Hypoglycemia

Cox DJ, Gonder-Frederick L, Ritterband L, Clarke W, Kovatachev BP: Prediction of severe hypoglycemia. Diabetes Care 30:1370–1373, 2007 Objective. Research demonstrates the importance of achieving near-normal glycemia in the prevention of diabetes-related complications.1 However, in an effort to attain euglycemia, one runs the risk for hypoglycemia.2 Severe hypoglycemia (SH), a low blood glucose resulting in stupor, seizure, or unconsciousness, prohibits self-treatment. To prevent SH, one must be able to anticipate when an event may occur to initiate treatment steps or identify warning signs and take action to stop further progression. The objective of this study was to test methods for predicting SH by using blood glucose meter readings. Design and methods. One hundred adults with type 1 diabetes and 79 insulin-using adults with type 2 diabetes participated in this study. Their self-monitoring of blood glucose (SMBG) readings were stored on memory meters, and the patients were asked biweekly about the occurrence of SH. Results. Relative risk (RR) for SH, quantified by the ratio of an individual's low blood glucose index (LBGI) based on the previous 150 SMBG readings to the LBGI based on recent SMBG readings, increased significantly in the 24-hour period before SH episodes in individuals with either type 1 or type 2 diabetes. An algorithm detected 58% of impending SH episodes when three SMBG readings …

Recombinant Porcine Factor VIII Corrects Thrombin Generation and Improves Clot Structure In Vitro in Plasma Containing Anti-Factor VIII Inhibitory Antibodies

Abstract 2282 Introduction:Treatment of bleeding episodes in patients with hemophilia A who have developed inhibitory antibodies can be challenging. Using human factor VIII (FVIII) and, historically, porcine FVIII in patients with a low inhibitor titer are therapeutic options, and provide ease of monitoring. A B-domain deleted recombinant porcine FVIII (rpFVIII; OBI-1), which may possess low cross-reactivity to anti-human FVIII antibodies, is being investigated for the treatment of bleeding episodes in individuals with congenital hemophilia A and inhibitors, and in those with acquired hemophilia. The in vitro capacity of this molecule to correct hemostasis has been further characterized. Methods:This is an international, multicenter in vitro study. Individuals with hemophilia A and inhibitor antibodies were recruited during routine out-patient visits between January 2011 and March 2011. Written and signed informed consent was obtained prior to venepuncture. Blood was obtained from volunteers with congenital hemophilia A and inhibitors attending routine visits at participating hemophilia treatment centers. A single blood sample was obtained from consenting individuals under protocols approved by Institutional Review Boards/Ethical Committees. In vitro spiking experiments with OBI-1 were conducted using FVIII-deficient plasma with and without anti-FVIII inhibitory activity. Three control inhibitor plasmas were provided, composed of FVIII deficient plasma to which the anti-C1 monoclonal antibody (MAb) to human FVIII (Sanquin, Amsterdam, the Netherlands) was added at two concentrations to reach anti-human FVIII inhibitory activity of 4.9 Bethesda Units (BU)/mL and 32.8 BU/mL with anti-porcine anti-FVIII inhibitory activity of 2.7 BU/mL and 19.1 BU/mL, respectively; and FVIII deficient plasma to which “polyclonal” mixture of the anti-C1 MAb, along with an anti-A2 and 2 anti-C2 MAbs was added. Plasma from eight patients with hemophilia A and inhibitors was tested. Hemostatic correction by OBI-1 was assessed by thrombin generation measurement (Calibrated Analytical Thrombography assay, Synapse BV, Maastricht, The Netherlands) and clot structure using electron microscopy. Epitope mapping of the inhibitor patient plasma was undertaken at a central laboratory (Atlanta, Georgia, USA) using an Enzyme-Linked Immunosorbent Assay (ELISA) with human/porcine FVIII hybrids as the antigen. Results:The results showed a dose-dependent and anti-porcine titer dependent correction of thrombin generation parameters (peak and ETP) with OBI-1 at concentrations equivalent to 100 IU/dL, 200 IU/dL, and 400 IU/dL, which paralleled a correction of the clot structure (number and diameter of fibrin fibres). These results were only dependent on the anti-porcine titer. In samples with high titers of anti-porcine inhibitor (>10 BU), little or no restoration of the diminished thrombin generation was observed when various OBI-1 concentrations were added to the plasma. In the plasmas with high anti-human titers (≥10 BU/mL) the dominant epitope was C2 in 3 plasmas, A2 in 1 plasma, and indeterminate in 3 plasmas. The plasmas with no restoration of the thrombin generation with even the highest dose of OBI-1 all had antibody detected to more than one domain of FVIII or were not able to be mapped due to high porcine cross-reactivity. Conclusion:In vitro data obtained with spiking experiments using OBI-1 indicate that it has the potential to correct surrogate markers of hemostasis depending on the anti-porcine FVIII titer which may translate into in vivo effectiveness. Further investigation into the epitope specificity of responsive and non-responsive inhibitor plasmas correlation with effectiveness is warranted. Disclosures:Negrier:Inspiration Biopharmaceuticals: Honoraria, Research Funding. Meeks:Inspiration Biopharmaceuticals: Research Funding. Oldenburg:SOBI: Membership on an entity's Board of Directors or advisory committees; Catalyst: Membership on an entity's Board of Directors or advisory committees; Inspiration: Consultancy, Honoraria, Research Funding; LFB: Consultancy; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Honoraria; Octapharma: Consultancy, Honoraria, Research Funding. Bordet:Inspiration Biopharmaceuticals: Research Funding. Poetzsch:Inspiration Biopharmaceuticals: Research Funding. Al Dieri:Synapse BV: Employment. Dargaud:Inspiration Biopharmaceuticals: Research Funding. Hemker:Synapse BV: Employment. Eckmann:Sanquin Diagnostic Services: Employment. Gomperts:Inspiration Biopharmaceuticals: Employment. Lee:Inspiration Biopharmaceuticals: Employment.

Cardiopulmonary bypass in malignant hyperthermia susceptible patients: A systematic review of published cases

Malignant hyperthermia susceptibility is an important risk factor during general anesthesia. Affected patients have an asymptomatic but potentially lethal hypermetabolic reaction after contact with volatile anesthetics or succinylcholine. Classic symptoms include hemodynamic instability, combined with acidosis, rigor, and hyperthermia. During cardiopulmonary bypass, these signs may be obscured, delaying correct diagnosis and lifesaving treatment. Malignant hyperthermia-susceptible individuals are more sensitive to heat and stress, so rewarming and catecholamine administration may trigger an episode, necessitating prophylactic measures. This systematic review identified typical malignant hyperthermia symptoms during cardiopulmonary bypass and investigated other factors in cardiac surgery that might trigger an episode in susceptible individuals. Approaches used to treat and prevent malignant hyperthermia during cardiopulmonary bypass were systematically analyzed. We conducted a systematic search for reports about malignant hyperthermia and cardiopulmonary bypass. Search terms included malignant hyperthermia and cardiopulmonary bypass, extracorporeal circulation, or cardiac surgery. We found 24 case reports and case series including details of 26 patients. In 14 cases, malignant hyperthermia crises during or shortly after cardiopulmonary bypass were described. Fourteen reports discussed prevention of an episode. Early symptoms of a malignant hyperthermia episode include excessive carbon dioxide production and metabolic acidosis. Massively increased creatine kinase levels are a strong indicator of a malignant hyperthermia reaction. Rewarming is associated with development of clinical signs of malignant hyperthermia. In potentially susceptible patients, apart from avoiding classic trigger substances, aggressive rewarming should not be applied. Hemodynamic instability in conjunction with the described symptoms should result in a diagnostic algorithm.

S22-01 - Immune activation in psychiatric and pre-psychiatric disease

Accumulating evidence indicates an activated immune system as a vulnerability factor for the development of schizophrenia (SCZ) and bipolar disorder (BD). In support we detected:1.Monocytosis and monocyte activation (e.g. a specific gene expression signature of inflammation related genes in a coherent pattern) in naturalistically treated SCZ and BD patients, and2.T cell activation in the same patients, be it that it were Treg cells that were more numerous in BD, while in SCZ Treg and Th17 cells numbers were raised.We also tested 70–80 children at ages of 16 and 21 yrs, having1-2 parent(s) with BD. This offspring has a higher chance of developing a mood disorder and over 25% had developed a mood disorder at 21 yrs. Not only the offspring with a lifetime diagnosis of mood disorder had activated monocytes and more Treg cells (similar as BD patients), but also around 40–50% of euthymic offspring had this immune activation profile. Importantly children who were psychiatrically healthy at 16yrs, and had developed a mood disorder at 21 yrs of age, all had activated monocytes at 16yrs.Our data show that both the monocyte and T cell arm of the immune system are activated in SCZ and BD, this activation preceding the onset of first episodes in individuals at risk. Our approach opens new avenues for early detection of psychiatric disease based on the immune state of individuals at risk, enabling possible selection of those individuals who might benefit from an immune modulation treatment to prevent disease.

Exposure and safety of higher doses of recombinant factor VIIa ≥250 μg kg−1 in individuals with congenital haemophilia complicated by alloantibody inhibitors: the Haemophilia and Thrombosis Research Society Registry experience (2004-2008)

Recombinant factor VIIa (rFVIIa) is a well-established treatment for managing bleeding episodes in individuals with congenital haemophilia complicated by alloantibody inhibitors (CHwI). The safety and efficacy of standard dosing (90-120 μg kg(-1) every 2-3 h) are well-established; however, the desire to optimize therapy with one or more higher doses instead of multiple lower doses has created a need for evidence of the safety and efficacy of such regimens. Analysis of data from the Haemophilia and Thrombosis Research Society (HTRS) Registry was performed on episodes where doses of ≥250 μg kg(-1) were reported. From 2041 rFVIIa-treated bleeds, 172 bleeding episodes were identified in 25 individuals with CHwI who were treated with ≥1 higher doses (≥250 μg kg(-1) , ≥270 μg kg(-1) or ≥300 μg kg(-1) ) of rFVIIa between January 2004 and November 2008. Bleeds occurred in individuals ranging in age from 0.4 to 41.7 years who were predominantly non-Hispanic and white (40%) with haemophilia A (88%). Bleed types most frequently treated with higher doses of rFVIIa were spontaneous (62-65%) or traumatic (27-32%). Bleed locations most frequently treated with higher doses of rFVIIa were joint (60-68%) or muscle (20-25%). A total of 1521 rFVIIa doses were administered (median, three doses per bleed); 26% were 250 μg kg(-1) or higher (initial dose, 82%). Bleeding stopped in 93% (160/172) of bleeds treated with rFVIIa 250 μg kg(-1) or higher. No serious adverse drug-related events or thrombotic complications were reported. This data analysis from the HTRS Registry provides evidence of the safe and effective use of higher doses of rFVIIa (≥250 μg kg(-1) ) in US practice.

Relationship between motivation for weight loss and dieting and binge eating in a representative population survey

To investigate the relationship between reasons for weight loss and previous dieting attempts and current binge-eating episodes in overweight and obese individuals. For the n = 355 interviewees of a representative sample of Swiss inhabitants (n = 1,000) reporting a body mass index (BMI) of ≥25, the Weight Loss Motivation Questionnaire--distinguishing between the three scales: health, appearance in relation to oneself, and appearance in relation to others--was assessed. Pearson's and Spearman's rank correlation coefficients and the partial correlation coefficient controlling for age, sex, socioeconomic status, and BMI were calculated. Number of previous diets was significantly correlated with all three subscales, whereas presence of binge-eating episodes was only significantly correlated with appearance in relation to oneself. Dieting and binge-eating behavior are differently associated with reasons for weight loss; better matching of treatments to patients' individual needs might improve the high dropout rates observed in weight loss treatments and enhance weight loss success.

Acute treatment with cannabinoid receptor agonist WIN55212.2 improves prepulse inhibition in psychosocially stressed mice

Cannabis, similar to psychosocial stress, is well known to exacerbate psychotic experiences and can precipitate psychotic episodes in vulnerable individuals. Cannabinoid receptors 1 (CB1) are widely expressed in the brain and are particularly important to mediate the effects of cannabis. Chronic cannabis use in patients and chronic cannabinoids treatment in animals is known to cause reduced prepulse inhibition (PPI). Similarly, chronic psychosocial stress in mice impairs PPI. In the present study, we investigated the synergistic effects of substances modulating the CB1-receptors and chronic psychosocial stress on PPI.For this purpose, adult C57Bl/6J mice were exposed to chronic psychosocial stress using the resident-intruder paradigm. The cannabinoid receptor agonist WIN55212.2 served as a surrogate marker for the effects of cannabis in the brain. After exposure to stress mice were acutely injected with WIN55212.2 (3mg/kg) with or without pre-treatment with Rimonabant (3mg/kg), a specific CB1-receptor antagonist, and subjected to behavioral testing.Stressed mice displayed a higher vulnerability to WIN55212.2 in the PPI test than control animals. The effects of WIN55212.2 on PPI were antagonized by Rimonabant suggesting an involvement of CB1-receptors in sensorimotor gating. Interestingly, WIN55212.2 increased PPI in psychosocially stressed mice although previous studies in rats showed the opposite effects. It may thus be possible, that depending on the doses of cannabinoids/CB1-receptor agonists applied and environmental conditions (psychosocial stress), opposite effects can be evoked in different experimental animals.Taken together, our data imply that CB1-receptors might play a crucial role in the synergistic effects of psychosocial stress and cannabinoids in brain.

Sampling strategies to measure the prevalence of common recurrent infections in longitudinal studies

BackgroundMeasuring recurrent infections such as diarrhoea or respiratory infections in epidemiological studies is a methodological challenge. Problems in measuring the incidence of recurrent infections include the episode definition, recall error, and the logistics of close follow up. Longitudinal prevalence (LP), the proportion-of-time-ill estimated by repeated prevalence measurements, is an alternative measure to incidence of recurrent infections. In contrast to incidence which usually requires continuous sampling, LP can be measured at intervals. This study explored how many more participants are needed for infrequent sampling to achieve the same study power as frequent sampling.MethodsWe developed a set of four empirical simulation models representing low and high risk settings with short or long episode durations. The model was used to evaluate different sampling strategies with different assumptions on recall period and recall error.ResultsThe model identified three major factors that influence sampling strategies: (1) the clustering of episodes in individuals; (2) the duration of episodes; (3) the positive correlation between an individual's disease incidence and episode duration. Intermittent sampling (e.g. 12 times per year) often requires only a slightly larger sample size compared to continuous sampling, especially in cluster-randomized trials. The collection of period prevalence data can lead to highly biased effect estimates if the exposure variable is associated with episode duration. To maximize study power, recall periods of 3 to 7 days may be preferable over shorter periods, even if this leads to inaccuracy in the prevalence estimates.ConclusionChoosing the optimal approach to measure recurrent infections in epidemiological studies depends on the setting, the study objectives, study design and budget constraints. Sampling at intervals can contribute to making epidemiological studies and trials more efficient, valid and cost-effective.

Comparison of heart rate variability and cardiac arrhythmias in polluted and clean air episodes in healthy individuals

Pathophysiological mechanisms and pathways linking cardiovascular mortality and morbidity with air pollution were recently hypothesized. The present study evaluated association between air pollution and changes in heart rate variability as a marker of cardiac autonomic function in healthy individuals, and also determined the frequency of cardiac arrhythmias and QT interval changes on polluted compared to unpolluted days. Continuous Holter electrocardiography (ECG) monitoring was conducted on 21 young healthy individuals in the two episodes of clean air and elevated air pollution in Tehran. All subjects underwent a medical history review, a physical examination and echocardiography in order to rule out structural heart diseases. Measured pollutants and parameters included NO(2), CO(2), O(3), SO(2), and PM10, which all showed significantly higher concentrations on polluted days. Holter parameters were measured for 24-h time segments and compared. Maximum heart rate was significantly lower in polluted air conditions in comparison with clean air conditions (115.1±32.2 vs. 128.9±17.7), and the square root of the mean of squared differences between adjacent NN intervals (r-MSSD) was higher in polluted air compared to clean air (99.0±58.2 vs. 58.5±26.4). Also, the occurrence of nonsustained supraventricular tachycardia was reported in 42.9% of participants in air pollution episodes, whereas this arrhythmia was not seen in clear air conditions (p=0.001). Changes in air pollution indices may lead to the occurrence of nonsustained supraventricular tachycardia, a slight reduction in maximum heart rate, and an increase in r-MSSD in healthy individuals. Air quality monitoring in cities associated with a high exposure to air pollutants is recommended in order to prevent such events.

Depressive symptoms and momentary affect: the role of social interaction variables

Interpersonal functioning may be one important factor in the development and course of depression symptomatology. This study used ecological momentary assessment to test the associations among depressive symptoms, social experiences and momentary affect in women. Middle-aged women (N=108, M age: 41.6 years, 81% White) completed diary questions on handheld computers for 2 days. Diary items assessed social (conflictive versus supportive) and affective (negative versus positive) experiences at random times during the day. Women also completed a self-report measure of recent depressive symptoms. Multilevel modeling analyses showed that higher levels of symptoms of depression were related to higher negative affect and lower positive affect both directly and indirectly, through experiences of social conflict. Depressive symptoms were not significantly related to socially supportive interactions. In an alternative model testing the reverse association, neither positive nor negative affect significantly predicted social experiences. Generalizability is limited by the homogenous small sample and strict inclusionary criteria (working full-time or part-time, cohabitating or married, healthy). Due to the cross sectional nature of the data as well as the manner in which social and affective experiences were assessed, definitive conclusions regarding the temporal associations among depression symptoms, social functioning, and affect are not possible. Results are consistent with prior reports suggesting the salience of socially conflictive experiences, and the role of affect, in the etiology and maintenance of depression symptoms. Interventions that attempt to decrease socially conflictive experiences via cognitive-behavioral skills training, whereas concomitantly targeting positive and negative affect, could help prevent the development of full-blown depressive episodes in vulnerable individuals.

Use of Single Dose of rFVIIa in Congenital Hemophilia: Analysis of Data Capture from the Hemophilia and Thrombosis Research Society Registry (2004–2008)

The recommended dose of recombinant factor VIIa (rFVIIa, NovoSeven®) is 90 mcg/kg every 2–3 hours. The Home Treatment Study demonstrated an average of 2.2 doses of 90 mcg/kg were required to treat mild to moderate bleeds. Since it is recognized that a single dose administered shortly after a bleed, if equally effective, would be more convenient and possibly could reduce bleeding morbidity, this study examined the experience registered with the use of single rFVIIa doses in the United States.The HTRS database contains patient data relating to hemophilia treatment and related disorders, and in particular the treatment of acute bleeding episodes in individuals with hemophilia complicated by anti-factor VIII (FVIII) or IX (FIX) alloantibody inhibitors. Between January 2004 and March 2008, the database contained information on over 5,000 bleeding episodes. The data for patients receiving only a single bolus intravenous dose of rFVIIa and no additional treatment were evaluated. The parameters assessed included patient demographics, bleed location, bleed type (specifically joint and muscle bleeds), and dose.Of 2,532 patients who received rFVIIa, 70 with congenital hemophilia A (n=63) or B (n=7) and inhibitors experienced 508 bleeding episodes that were treated solely with a single dose of rFVIIa. The mean (median, range) age at the time of bleed was 12.7 years (8.2, 0.6–60.4). Mean titers for anti-FVIII and anti-FIX were 62.2 BU (15.0, 0–1408) and 6.8 BU (1.3, 0–31.7), respectively. The bleed sites recorded were joints (271 bleeds [53%], including 55 in target joints [20.2% of joint bleeds]), muscle (78, 15%), mucosal (45, 9%), intracranial (25, 5%), and subcutaneous (21, 4%). Joint bleeds occurred primarily in the ankles (124 bleeds), elbows (61 bleeds) and knees (53 bleeds).For 508 bleeds treated with a single dose of rFVIIa, the mean (median, range) dose was 119.5 mcg/kg (100, 25–500) with 20 of those doses ≥270 mcg/kg. Patients with joint bleeds were treated with 123.1 mcg/kg (100, 25–500), target joint bleeds with 155.3 (140, 50–393), and those with the muscle bleeds received 120.1 mcg/kg (100, 50–500). The most common single dose regimen overall and for the joint and muscle bleeds was 90 mcg/kg rFVIIa.The majority of bleeds (424, 82.7%) were treated at home, but bleeds were also treated at Hemophilia Treatment Centers (61, 12.0%) and in the emergency room (15, 3.0%). Overall, physician reported “bleeding stopped” in 97% of the 494 bleeds, 97% of hemarthroses, 96% of target joint hemarthroses and 96% of muscle bleeds. For the remaining 14 episodes, although documentation did not indicate “bleeding stopped”, no other medications were recorded.There were no serious adverse drug reactions.Registry data can only demonstrate the treatment reported in selected bleeds captured, and the analysis here specifically examined bleeds treated with only a single dose either because of bleed resolution or by physician/patient choice. The data analyzed here demonstrate single doses of rFVIIa of up to 500 mcg/kg (mean 119 mcg/kg) for mild to moderate bleeds effectively resolved bleeds in 97%, including hemarthrosis, target joints hemarthrosis, and muscle bleeds. These data support the possibility that rFVIIa can be administered in a single bolus dose with equivalent or superior efficacy as multiple lower doses for bleeding episodes treated as part of a home therapy regimen. While 3 randomized trials have examined the equivalence of a single dose of 270 mcg/kg with 3 doses of 90 mcg/kg, these data suggest that single doses of rFVIIa therapy in the real world often were empirically titrated on a patient specific basis, according to the severity and site of the bleeding episode. These registry data provide justification for prospective, randomized, single dose titration trials of rFVIIa or future analogues.

96: Spectrum and prevalence of prothrombotic single nucleotide polymorphism profiles in the Greek cypriot population

This study was performed to establish the allele, genotype and genotype combination/SNP (single nucleotide polymorphism) profile frequencies in the general population of Cyprus for 6 genes implicated in thrombotic disorders. The genes with their respective functional polymorphisms were the following: factor V (G1691A), prothrombin/factor II (G20210A), methylenetetrahydrofolate reductase (C677T), platelet glycoprotein receptor IIIa (P1A1/A2), b-fibrinogen (G/A-455) and plasminogen activator inhibitor-type 1 (4G/5G).DNA samples from 121 unrelated individuals were used for this epidemiological study. The polymerase chain reaction followed by restriction digestion were used to genotype the 6 different polymorphic loci. Allele and genotype frequencies were established and shown to be in Hardy-Weinberg equilibrium.Mutant allele frequencies for the 6 genes were as follows: factor V-4%, prothrombin-2%, methylenetetrahydrofolate reductase -39%, platelet glycoprotein receptor IIIa-16%, beta-fibrinogen-17% and plasminogen activator inhibitor - type 1-46%. Combined defects occurred which may increase the risk for vascular events, 33% of individuals (39/118) had 3 or more of the above mutations.As in other European populations, prospective case-control studies to estimate the risk for deep vein thrombosis (DVT) and ischemic episodes with respect to genetic and environmental risk factors should be performed. Thrombophilia screening should be applied for primary and secondary prevention of thrombotic episodes in susceptible individuals on the island of Cyprus. Individuals targeted for such screening include those with the following: a positive family history for thrombosis; a previous DVT or other ischemic episode; prior exposure to circumstantial risk factors and in the presence of echolucent plaques.