Hemodynamic changes in systolic and diastolic function during isoproterenol challenge predicts symptomatic response to myectomy in hypertrophic cardiomyopathy with labile obstruction.

PubMed

Prasad, Megha; Geske, Jeffrey B; Sorajja, Paul; Ommen, Steve R; Schaff, Hartzell V; Gersh, Bernard J; Nishimura, Rick A

2016-11-15

We aimed to assess the utility of changes in systolic and diastolic function by isoproterenol challenge in predicting symptom resolution post-myectomy in selected patients with hypertrophic cardiomyopathy (HCM) and labile obstruction. In a subset of symptomatic HCM patients without resting/provocable obstruction on noninvasive assessment, isoproterenol challenge during hemodynamic catheterization may elicit labile left ventricular outflow tract (LVOT) obstruction, and demonstrate the effect of obstruction on diastolic function. These changes may determine whether patients achieve complete symptom resolution post-myectomy. Between February 2003 and April 2009, 18 symptomatic HCM patients without LVOT obstruction on noninvasive testing underwent isoproterenol provocation and septal myectomy due to presence of provocable gradient and were followed for 4 (IQR 3-7) years. Thirteen (72.2%) had complete symptom resolution, while 5 (27.8%) had improved, but persistent symptoms. Those with provoked gradient >100 mm Hg or increase in left atrial pressure (LAP) with isoproterenol had symptom resolution. Symptomatic HCM patients without LVOT gradient on noninvasive testing may demonstrate labile obstruction with isoproterenol. With isoproterenol, patients with high LVOT gradient or increase in LAP concomitant with an increase in gradient achieved complete symptom resolution post-myectomy. Thus, improved diastolic filling as well as outflow gradient production in patients with HCM may predict symptom response to myectomy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Serotonin Augmentation Reduces Response to Attack in Aggressive Individuals

PubMed Central

Berman, Mitchell E.; McCloskey, Michael S.; Fanning, Jennifer R.; Schumacher, Julie A.; Coccaro, Emil F.

2009-01-01

We tested the theory that central serotonin (5- hydroxytryptamine, or 5-HT) activity regulates aggression by modulating response to provocation. Eighty men and women (40 with and 40 without a history of aggression) were randomly assigned to receive either 40 mg of paroxetine (to acutely augment serotonergic activity) or a placebo, administered using double-blind procedures. Aggression was assessed during a competitive reaction time game with a fictitious opponent. Shocks were selected by the participant and opponent before each trial, with the loser on each trial receiving the shock set by the other player. Provocation was manipulated by having the opponent select increasingly intense shocks for the participant and eventually an ostensibly severe shock toward the end of the trials. Aggression was measured by the number of severe shocks set by the participant for the opponent. As predicted, aggressive responding after provocation was attenuated by augmentation of serotonin in individuals with a pronounced history of aggression. PMID:19422623

Muscle Weakness in the Empty and Full Can Tests Cannot Differentiate Rotator Cuff Tear from Cervical Spondylotic Amyotrophy: Pain Provocation is a Useful Finding.

PubMed

Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Sakamoto, Yoshihiro; Tanaka, Yasuhito

2017-01-01

Rotator cuff tears and cervical spondylotic amyotrophy (CSA) are often confused as the main symptom in those with difficulty in shoulder elevation. Empty and full can tests are frequently used for the clinical diagnosis of rotator cuff tears. The aim of the present study was to investigate whether the empty and full can test results can help differentiate rotator cuff tears from CSA. Twenty-seven consecutive patients with rotator cuff tears and 25 with CSA were enrolled. We prospectively performed empty and full can tests in patients with rotator cuff tears and CSA. The following signs were considered positive: (a) muscle weakness during the empty can test, (b) muscle weakness during the full can test, (c) pain provocation during the empty can test, and (d) pain provocation during the full can test. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of rotator cuff tears for each positive finding. The sensitivity and specificity of each index were as follows (sensitivity, specificity, PPV, NPV): (a) 77.8%, 0%, 45.7%, 0%; (b) 66.7%, 4.0%, 42.9%, 10.0%; (c) 88.9%, 96.0%, 96.0%, 88.9%; and (d) 74.1%, 96.0%, 95.2%, 77.4%. There were significant differences for each index. Muscle weakness during the empty and full can tests was not useful in differentiating rotator cuff tears from CSA because of low specificity and PPV. However, pain provocation was useful in differentiating these two conditions because of high specificity and PPV.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

PubMed

Kwon, Hyemi; Kim, Won Gu; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin Sook; Shong, Young Kee; Kim, Won Bae

2016-06-01

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

PubMed Central

Kwon, Hyemi; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin-Sook; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. Methods This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Results Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. Conclusion TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease. PMID:27118279

P3 and provoked aggressive behavior.

PubMed

Fanning, Jennifer R; Berman, Mitchell E; Long, James M

2014-01-01

Cognitive and biological processes play a role in human aggression. However, relatively little is known about the neural correlates of cognitive processes in aggressive individuals, particularly as they unfold during an aggressive encounter. We investigated whether the P3 event-related potential (ERP) discriminates aggressive versus nonaggressive individuals during a provocative, aggressive encounter. Forty-eight participants (23 men and 25 women) were classified as aggressive or nonaggressive based on self-reported life history of aggression. Aggressive behavior was assessed using a modification of a well-validated laboratory task during which the participant and a fictitious opponent ostensibly delivered and received noise blasts of low, medium, and high intensity. Provocation was manipulated by altering the level of noise set by the opponent. Aggression was defined as the number of high-intensity noise blasts the participant set for the opponent. As predicted, P3 amplitude in response to provocation differed as a function of aggressive history. Nonaggressive individuals showed enhanced P3 when provoked by the opponent relative to low provocation, but this effect was absent in aggressive individuals. The results suggest that aggressive individuals engage fewer neural processing resources in response to provoking social cues, which may reflect aberrant cognitive and emotional processes.

Seasonal variation in onset and relapse of IBD and a model to predict the frequency of onset, relapse, and severity of IBD based on artificial neural network.

PubMed

Peng, Jiang Chen; Ran, Zhi Hua; Shen, Jun

2015-09-01

Previous research has yielded conflicting data as to whether the natural history of inflammatory bowel disease follows a seasonal pattern. The purpose of this study was (1) to determine whether the frequency of onset and relapse of inflammatory bowel disease follows a seasonal pattern and (2) to establish a model to predict the frequency of onset, relapse, and severity of inflammatory bowel disease (IBD) with meteorological data based on artificial neural network (ANN). Patients with diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) between 2003 and 2011 were investigated according to the occurrence of onset and flares of symptoms. The expected onset or relapse was calculated on a monthly basis over the study period. For artificial neural network (ANN), patients from 2003 to 2010 were assigned as training cohort and patients in 2011 were assigned as validation cohort. Mean square error (MSE) and mean absolute percentage error (MAPE) were used to evaluate the predictive accuracy. We found no seasonal pattern of onset (P = 0.248) and relapse (P = 0.394) among UC patients. But, the onset (P = 0.015) and relapse (P = 0.004) of CD were associated with seasonal pattern, with a peak in July and August. ANN had average accuracy to predict the frequency of onset (MSE = 0.076, MAPE = 37.58%) and severity of IBD (MSE = 0.065, MAPE = 42.15%) but high accuracy in predicting the frequency of relapse of IBD (MSE = 0.009, MAPE = 17.1%). The frequency of onset and relapse in IBD showed seasonality only in CD, with a peak in July and August, but not in UC. ANN may have its value in predicting the frequency of relapse among patients with IBD.

Increased serum brain-derived neurotrophic factor (BDNF) is predictive of cocaine relapse outcomes: A prospective study

PubMed Central

D’Sa, Carrol; Fox, Helen C.; Hong, Adam K.; Dileone, Ralph J.; Sinha, Rajita

2011-01-01

Background Cocaine dependence is associated with high relapse rates but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central Brain Derived Neurotrophic Factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and if it is predictive of subsequent relapse risk. Methods Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3 week abstinent cocaine-dependent inpatients (17M/18F) and 34 demographically matched hospitalized healthy control participants (17M/17F). Cocaine dependent individuals were prospectively followed on days 14, 30 and 90 post-treatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures. Results High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared to healthy control participants (p<.001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: HR: 1.09, p<.05), greater number of days (p<.05) and higher total amounts of cocaine used (p = .05). Conclusions High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence. PMID:21741029

Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

PubMed Central

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

2012-01-01

Objective Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a Bootstrapping procedure to test the indirect effects. Results Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally-based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. Conclusion The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse, and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, while affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. PMID:22390410

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

PubMed

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

Impulsivity and suicidality: the mediating role of painful and provocative experiences.

PubMed

Bender, Theodore W; Gordon, Kathryn H; Bresin, Konrad; Joiner, Thomas E

2011-03-01

Multiple studies have reported a link between high levels of impulsivity and suicidal behavior. Joiner's (2005) explanation for this link is that impulsive individuals have a greater tendency to experience painful and provocative events that habituate them to fear and pain, which leads to an acquired capability for engaging in suicidal behavior. Study 1 tested Joiner's (2005) hypothesis in a sample of 182 undergraduate students who completed self-report questionnaires on impulsivity, frequency of painful and provocative events, and acquired capability for suicide. In addition to self-report, pain tolerance (an aspect of acquired capability for suicide) was measured with a pressure algometer. Study 2 sought to replicate our findings from Study 1 in a sample of 516 clinical outpatients using a multi-faceted measure of impulsivity. Consistent with prediction, product of coefficients tests for mediation (MacKinnon et al., 2002) revealed that impulsivity has an indirect relationship with acquired capability for suicidal behavior, and that this relationship is mediated by painful and provocative events. Data from our studies are cross-sectional in nature, which does not allow for conclusions about the temporal ordering of our variables. In addition, self-report was used to measure most variables. Future research may benefit from a longitudinal design and the inclusion of other modes of assessment (e.g., behavioral measures of impulsivity). Our findings suggest that the link between impulsivity and suicidal behavior occurs because impulsive people tend to have a greater capability for suicidal behavior, which they have acquired through experiencing painful and provocative events. Copyright © 2010 Elsevier B.V. All rights reserved.

Exercise identity and attribution properties predict negative self-conscious emotions for exercise relapse.

PubMed

Flora, Parminder K; Strachan, Shaelyn M; Brawley, Lawrence R; Spink, Kevin S

2012-10-01

Research on exercise identity (EXID) indicates that it is related to negative affect when exercisers are inconsistent or relapse. Although identity theory suggests that causal attributions about this inconsistency elicit negative self-conscious emotions of shame and guilt, no EXID studies have examined this for exercise relapse. Weiner's attribution-based theory of interpersonal motivation (2010) offers a means of testing the attribution-emotion link. Using both frameworks, we examined whether EXID and attributional properties predicted negative emotions for exercise relapse. Participants (n = 224) read an exercise relapse vignette, and then completed EXID, attributions, and emotion measures. Hierarchical multiple regression models using EXID and the attributional property of controllability significantly predicted each of shame and guilt, R² adjusted = .09, ps ≤ .001. Results support identity theory suggestions and Weiner's specific attribution-emotion hypothesis. This first demonstration of an interlinking of EXID, controllability, and negative self-conscious emotions offers more predictive utility using complementary theories than either theory alone.

Comparison of Valsalva Maneuver, Amyl Nitrite, and Exercise Echocardiography to Demonstrate Latent Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy.

PubMed

Ayoub, Chadi; Geske, Jeffrey B; Larsen, Carolyn M; Scott, Christopher G; Klarich, Kyle W; Pellikka, Patricia A

2017-12-15

Guidelines recommend exercise stress echocardiogram (ESE) for patients with hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or provoked with Valsalva or amyl nitrite, to direct medical and surgical management. However, no study has directly compared all 3 methods. We sought to evaluate efficacy and degree of provocation of left ventricular outflow gradients by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between 2002 and 2015, resting echocardiograms and ESEs within 1 year were retrospectively reviewed. Gradients elicited by each provocation method were compared. Rest and ESE were available in 97 patients (mean age 54 ± 18 years, 57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34) with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE. ESE and amyl nitrite were able to provoke obstruction (≥30 mm Hg) and severe obstruction (≥50 mm Hg) more frequently than Valsalva. In patients with resting gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline echocardiographic parameter predicted provocable obstruction. In conclusion, ESE is clinically useful; however, different provocation maneuvers may be effective in different patients with HC, and all maneuvers may be required to provoke dynamic obstruction in symptomatic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Relapse prediction in Graves´ disease: Towards mathematical modeling of clinical, immune and genetic markers.

PubMed

Langenstein, Christoph; Schork, Diana; Badenhoop, Klaus; Herrmann, Eva

2016-12-01

Graves' disease (GD) is an important and prevalent thyroid autoimmune disorder. Standard therapy for GD consists of antithyroid drugs (ATD) with treatment periods of around 12 months but relapse is frequent. Since predictors for relapse are difficult to identify the individual decision making for optimal treatment is often arbitrary. After reviewing the literature on this topic we summarize important factors involved in GD and with respect to their potential for relapse prediction from markers before and after treatment. This information was used to design a mathematical model integrating thyroid hormone parameters, thyroid size, antibody titers and a complex algorithm encompassing genetic predisposition, environmental exposures and current immune activity in order to arrive at a prognostic index for relapse risk after treatment. In the search for a tool to analyze and predict relapse in GD mathematical modeling is a promising approach. In analogy to mathematical modeling approaches in other diseases such as viral infections, we developed a differential equation model on the basis of published clinical trials in patients with GD. Although our model needs further evaluation to be applicable in a clinical context, it provides a perspective for an important contribution to a final statistical prediction model.

Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis--results from the maintenance phase of the EXPO study.

PubMed

Labenz, J; Armstrong, D; Zetterstrand, S; Eklund, S; Leodolter, A

2009-06-01

Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration < or =5 years. Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.

The Importance of Prolonged Provocation in Drug Allergy - Results From a Danish Allergy Clinic.

PubMed

Fransson, Sara; Mosbech, Holger; Kappel, Mogens; Hjortlund, Janni; Poulsen, Lars K; Kvisselgaard, Ask D; Garvey, Lene H

Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. To evaluate drug allergy investigations on the basis of drug provocation, including prolonged provocation. Data from adult patients investigated for drug allergy in a Danish Allergy Clinic during the period 2010 to 2014 were entered into a database. Data included clinical details and results of provocations with suspected culprit drug (for penicillins performed only in specific IgE-negative patients). If provocation was negative on first dose, treatment was continued for 3 to 10 days. A total of 1,913 provocations were done in 1,659 patients, median age 46 years, of whom 1,237 (74.6%) were females. Drugs investigated were antibiotics, 1,776 (92.8%), of which 1,590 (89.5%) were penicillins; analgesics, 59 (3.1%); local anesthetics, 33 (1.7%); and other drugs, 45 (2.4%). In total, 211 of 1,913 (11.0%) provocations were positive. Causes were antibiotics, 198 (93.8%), of which 167 (84.3%) were penicillins; analgesics, 7 (3.3%); local anesthetics, 0; and other drugs, 6 (2.8%). Only 43 (20.4%) provocations were positive on first dose, whereas 95 (45.0%) turned positive more than 3 days later. Only 11.0% of the provocations were positive. Importantly, only 1 of 5 patients tested positive on the first dose, indicating that prolonged exposure should always be considered when drug provocation is included in allergy investigations. Most provocations were with penicillins, reflecting the pattern of antibiotic use in Denmark, which differs from that in other countries, especially outside Northern Europe. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

When do normative beliefs about aggression predict aggressive behavior? An application of I3 theory.

PubMed

Li, Jian-Bin; Nie, Yan-Gang; Boardley, Ian D; Dou, Kai; Situ, Qiao-Min

2015-01-01

I(3) theory assumes that aggressive behavior is dependent on three orthogonal processes (i.e., Instigator, Impellance, and Inhibition). Previous studies showed that Impellance (trait aggressiveness, retaliation tendencies) better predicted aggression when Instigator was strong and Inhibition was weak. In the current study, we predicted that another Impellance (i.e., normative beliefs about aggression) might predict aggression when Instigator was absent and Inhibition was high (i.e., the perfect calm proposition). In two experiments, participants first completed the normative beliefs about aggression questionnaire. Two weeks later, participants' self-control resources were manipulated either using the Stroop task (study 1, N = 148) or through an "e-crossing" task (study 2, N = 180). Afterwards, with or without being provoked, participants played a game with an ostensible partner where they had a chance to aggress against them. Study 1 found that normative beliefs about aggression negatively and significantly predicted aggressive behavior only when provocation was absent and self-control resources were not depleted. In Study 2, normative beliefs about aggression negatively predicted aggressive behavior at marginal significance level only in the "no-provocation and no-depletion" condition. In conclusion, the current study provides partial support for the perfect calm proposition and I(3) theory. © 2015 Wiley Periodicals, Inc.

Rurality and Patterns of Social Disruption.

ERIC Educational Resources Information Center

Wilkinson, Kenneth P.

1984-01-01

Argues that structural cleavages provoke social disruptions where opportunities are conducive. Thus, combinations of rurality with particular structural cleavages predict specific disruption patterns. Data from northeastern United States indicate that rurality, combined with other population characteristics (provocation, ascriptive inequality,…

Trait impulsive choice predicts resistance to extinction and propensity to relapse to cocaine seeking: a bidirectional investigation.

PubMed

Broos, Nienke; Diergaarde, Leontien; Schoffelmeer, Anton Nm; Pattij, Tommy; De Vries, Taco J

2012-05-01

Despite the strong association between impulsivity and addiction in humans, it is still a matter of debate whether impulsive choice predisposes to, or results from, drug dependence. Furthermore, it is unknown whether treating impulsivity can protect against relapse propensity. Therefore, this study explored the bidirectional relationship between impulsive choice and cocaine taking and seeking in rat behavioral models. In experiment 1, to determine whether impulsive choice predisposes to cocaine taking or seeking, rats were selected based on trait impulsivity in a delayed reward task and subsequently compared on various stages of cocaine self-administration (SA). To examine the consequence of cocaine intake on impulsive choice, impulsivity was monitored once a week throughout various stages of cocaine SA. To determine whether treating impulsive choice can protect against relapse propensity, in experiment 2, impulsive choice was manipulated by pharmacological interventions and cocaine-associated contextual cues. Trait impulsive choice as determined in experiment 1 predicted high extinction resistance and enhanced propensity to context-induced relapse in the cocaine SA model, whereas cocaine intake did not alter impulsive choice. Furthermore, acute changes in impulsive choice were not related to rates of context-induced relapse. Taken together, the current data indicate that trait impulsive choice predicts persistent cocaine seeking during extinction and enhanced propensity to relapse, whereas acute manipulations of impulsive choice had no favorable outcomes on relapse measures. These observations suggest that trait impulsivity can be used as a predictive factor for addiction liability, but treating this impulsivity does not necessarily protect against relapse.

Comparing early signs and basic symptoms as methods for predicting psychotic relapse in clinical practice.

PubMed

Eisner, Emily; Drake, Richard; Lobban, Fiona; Bucci, Sandra; Emsley, Richard; Barrowclough, Christine

2018-02-01

Early signs interventions show promise but could be further developed. A recent review suggested that 'basic symptoms' should be added to conventional early signs to improve relapse prediction. This study builds on preliminary evidence that basic symptoms predict relapse and aimed to: 1. examine which phenomena participants report prior to relapse and how they describe them; 2. determine the best way of identifying pre-relapse basic symptoms; 3. assess current practice by comparing self- and casenote-reported pre-relapse experiences. Participants with non-affective psychosis were recruited from UK mental health services. In-depth interviews (n=23), verbal checklists of basic symptoms (n=23) and casenote extracts (n=208) were analysed using directed content analysis and non-parametric statistical tests. Three-quarters of interviewees reported basic symptoms and all reported conventional early signs and 'other' pre-relapse experiences. Interviewees provided rich descriptions of basic symptoms. Verbal checklist interviews asking specifically about basic symptoms identified these experiences more readily than open questions during in-depth interviews. Only 5% of casenotes recorded basic symptoms; interviewees were 16 times more likely to report basic symptoms than their casenotes did. The majority of interviewees self-reported pre-relapse basic symptoms when asked specifically about these experiences but very few casenotes reported these symptoms. Basic symptoms may be potent predictors of relapse that clinicians miss. A self-report measure would aid monitoring of basic symptoms in routine clinical practice and would facilitate a prospective investigation comparing basic symptoms and conventional early signs as predictors of relapse. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Predictors of relapse in patients with major depressive disorder in a 52-week, fixed dose, double blind, randomized trial of selegiline transdermal system (STS).

PubMed

Jang, Saeheon; Jung, Sungwon; Pae, Chiun; Kimberly, Blanchard Portland; Craig Nelson, J; Patkar, Ashwin A

2013-12-01

We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment. After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥ 14 and a CGI-S score of ≥ 3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse. For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis. While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD. © 2013 Published by Elsevier B.V.

Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

PubMed

Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

2017-09-01

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (>80%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Tridimensional Personality Questionnaire as a predictor of relapse in detoxified alcohol dependents. The European Fluvoxamine in Alcoholism Study Group.

PubMed

Meszaros, K; Lenzinger, E; Hornik, K; Füreder, T; Willinger, U; Fischer, G; Schönbeck, G; Aschauer, H N

1999-03-01

Personality traits have been found as strong predictors for treatment response in different psychiatric disorders. We administered the Tridimensional Personality Questionnaire, which measures the three personality dimensions: novelty seeking, harm avoidance (HA), and reward dependence, as introduced by Cloninger in a multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and Austria) with detoxified alcohol-dependent patients (n = 521). The objective of this study was to evaluate a possible predictive value of these three dimensions on relapse over 1 -year follow up. A logistic regression analysis showed that novelty seeking is a strong predictor for relapse in detoxified male alcoholics (p = 0.0007; p values adjusted for treatment), but not in females. In both sexes, HA and reward dependence were of no predictive value. However, we found a trend for significance of HA for predicting "early" relapse (4 weeks) in females (p = 0.074). Our results show that Tridimensional Personality Questionnaire personality traits have direct clinical applications for prediction of relapse in detoxified alcohol dependents and indicate the necessity of additional therapeutic treatment in risk groups.

Probability and predictors of relapse to smoking: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

PubMed Central

García-Rodríguez, Olaya; Secades-Villa, Roberto; Flórez-Salamanca, Ludwing; Okuda, Mayumi; Liu, Shang-Min; Blanco, Carlos

2013-01-01

Background The goal of this study was to estimate rates of relapse to smoking in the community and to identify predictors of relapse. Methods Data were drawn from the Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC). Logistic regression analyses were used to estimate the probability of relapse at Wave 2 among individuals who were abstinent at Wave 1 given length of abstinence as well as the presence of several sociodemographic, psychopathologic and substance use-related variables at Wave 1. Results The risk for relapse among individuals who had been abstinent for 12 months or less at the baseline assessment was above 50%. Among individuals who had been abstinent for over a year, risk of relapse decreased hyperbolically as a function of time, and stabilized around 10% after 30 years of abstinence. Although several sociodemographic, psychopathologic and tobacco-related variables predicted relapse in univariate analyses, only younger age at cessation and shorter duration of abstinence independently predicted risk of relapse in multivariable analyses. Conclusions The first year after a quit attempt constitutes the period of highest risk for relapse. Although the risk for relapse decreases over time, it never fully disappears. Furthermore, younger age at smoking cessation also increases the risk for relapse. This information may help develop more targeted and effective relapse prevention programs. PMID:23570817

[Application of Competing Risks Model in Predicting Smoking Relapse Following Ischemic Stroke].

PubMed

Hou, Li-Sha; Li, Ji-Jie; Du, Xu-Dong; Yan, Pei-Jing; Zhu, Cai-Rong

2017-07-01

To determine factors associated with smoking relapse in men who survived from their first stroke. Data were collected through face to face interviews with stroke patients in the hospital, and then repeated every three months via telephone over the period from 2010 to 2014. Kaplan-Meier method and competing risk model were adopted to estimate and predict smoking relapse rates. The Kaplan-Meier method estimated a higher relapse rate than the competing risk model. The four-year relapse rate was 43.1% after adjustment of competing risk. Exposure to environmental tobacco smoking outside of home and workplace (such as bars and restaurants) ( P =0.01), single ( P <0.01), and prior history of smoking at least 20 cigarettes per day ( P =0.02) were significant predictors of smoking relapse. When competing risks exist, competing risks model should be used in data analyses. Smoking interventions should give priorities to those without a spouse and those with a heavy smoking history. Smoking ban in public settings can reduce smoking relapse in stroke patients.

The Alcohol Relapse Situation Appraisal Questionnaire: Development and Validation

PubMed Central

Martin, Rosemarie A.; MacKinnon, Selene M.; Johnson, Jennifer E.; Myers, Mark G.; Cook, Travis A. R.; Rohsenow, Damaris J.

2011-01-01

Background The role of cognitive appraisal of the threat of alcohol relapse has received little attention. A previous instrument, the Relapse Situation Appraisal Questionnaire (RSAQ), was developed to assess cocaine users’ primary appraisal of the threat of situations posing a high risk for cocaine relapse. The purpose of the present study was to modify the RSAQ in order to measure primary appraisal in situations involving a high risk for alcohol relapse. Methods The development and psychometric properties of this instrument, the Alcohol Relapse Situation Appraisal Questionnaire (A-RSAQ), were examined with two samples of abstinent adults with alcohol abuse or dependence. Factor structure and validity were examined in Study 1 (N=104). Confirmation of the factor structure and predictive validity were assessed in Study 2 (N=161). Results Results demonstrated construct, discriminant and predictive validity and reliability of the A-RSAQ. Discussion Results support the important role of primary appraisal of degree of risk in alcohol relapse situations. PMID:21237586

Temperament and impulsivity predictors of smoking cessation outcomes.

PubMed

López-Torrecillas, Francisca; Perales, José C; Nieto-Ruiz, Ana; Verdejo-García, Antonio

2014-01-01

Temperament and impulsivity are powerful predictors of addiction treatment outcomes. However, a comprehensive assessment of these features has not been examined in relation to smoking cessation outcomes. Naturalistic prospective study. Treatment-seeking smokers (n = 140) were recruited as they engaged in an occupational health clinic providing smoking cessation treatment between 2009 and 2013. Participants were assessed at baseline with measures of temperament (Temperament and Character Inventory), trait impulsivity (Barratt Impulsivity Scale), and cognitive impulsivity (Go/No Go, Delay Discounting and Iowa Gambling Task). The outcome measure was treatment status, coded as "dropout" versus "relapse" versus "abstinence" at 3, 6, and 12 months endpoints. Participants were telephonically contacted and reminded of follow-up face to face assessments at each endpoint. The participants that failed to answer the phone calls or self-reported discontinuation of treatment and failed to attend the upcoming follow-up session were coded as dropouts. The participants that self-reported continuing treatment, and successfully attended the upcoming follow-up session were coded as either "relapse" or "abstinence", based on the results of smoking behavior self-reports cross-validated with co-oximetry hemoglobin levels. Multinomial regression models were conducted to test whether temperament and impulsivity measures predicted dropout and relapse relative to abstinence outcomes. Higher scores on temperament dimensions of novelty seeking and reward dependence predicted poorer retention across endpoints, whereas only higher scores on persistence predicted greater relapse. Higher scores on the trait dimension of non-planning impulsivity but not performance on cognitive impulsivity predicted poorer retention. Higher non-planning impulsivity and poorer performance in the Iowa Gambling Task predicted greater relapse at 3 and 6 months and 6 months respectively. Temperament measures, and specifically novelty seeking and reward dependence, predict smoking cessation treatment retention, whereas persistence, non-planning impulsivity and poor decision-making predict smoking relapse.

The Impact of Stressful Life Events on Alcohol Relapse: Findings from the Collaborative Longitudinal Personality Disorders Study.

PubMed

Reyes, Christina Delos; Pagano, Maria Elizabeth; Ronis, Robert J

2009-04-01

Alcohol relapse is impacted by a variety of environmental, interpersonal, and intrapersonal factors. We examined the interaction between stressful life events, personality disorder subtype, and alcohol relapse among individuals enrolled in the Collaborative Longitudinal Personality Disorders Study (CLPS). Negative life events predicted relapse in all subjects. In individuals with a history of an alcohol use disorder prior to study entry, positive life events also predicted alcohol relapse. Individuals with Antisocial Personality Disorder (ASPD) were found to be twice as likely to relapse in response to life stressors compared to individuals with Obsessive-Compulsive Personality Disorder (OCPD), who were half as likely to relapse in response to life stressors. Further analysis revealed that individuals with OCPD and no history of an alcohol use disorder were almost 10 times more likely to relapse in the face of a stressful romantic problem, while those with ASPD and a history of an alcohol use disorder were six times more likely to relapse in response to a stressful financial event. These findings have implications for both the assessment and the treatment of individuals who present with co-morbid personality and alcohol use disorders.

The Impact of Stressful Life Events on Alcohol Relapse: Findings from the Collaborative Longitudinal Personality Disorders Study

PubMed Central

Reyes, Christina Delos; Pagano, Maria Elizabeth; Ronis, Robert J.

2009-01-01

Alcohol relapse is impacted by a variety of environmental, interpersonal, and intrapersonal factors. We examined the interaction between stressful life events, personality disorder subtype, and alcohol relapse among individuals enrolled in the Collaborative Longitudinal Personality Disorders Study (CLPS). Negative life events predicted relapse in all subjects. In individuals with a history of an alcohol use disorder prior to study entry, positive life events also predicted alcohol relapse. Individuals with Antisocial Personality Disorder (ASPD) were found to be twice as likely to relapse in response to life stressors compared to individuals with Obsessive-Compulsive Personality Disorder (OCPD), who were half as likely to relapse in response to life stressors. Further analysis revealed that individuals with OCPD and no history of an alcohol use disorder were almost 10 times more likely to relapse in the face of a stressful romantic problem, while those with ASPD and a history of an alcohol use disorder were six times more likely to relapse in response to a stressful financial event. These findings have implications for both the assessment and the treatment of individuals who present with co-morbid personality and alcohol use disorders. PMID:21170176

Predictors of Relapse in Patients with Organizing Pneumonia

PubMed Central

Kim, Minjung; Seo, Hyewon; Shin, Kyung-Min; Lim, Jae-Kwang; Kim, Hyera; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

2015-01-01

Background Although organizing pneumonia (OP) responds well to corticosteroid therapy, relapse is common during dose reduction or follow-up. Predictors of relapse in OP patients remain to be established. The aim of the present study was to identify factors related to relapse in OP patients. Methods This study was retrospectively performed in a tertiary referral center. Of 66 OP patients who were improved with or without treatment, 20 (30%) experienced relapse. The clinical and radiologic parameters in the relapse patient group (n=20) were compared to that in the non-relapse group (n=46). Results Multivariate analysis demonstrated that percent predicted forced vital capacity (FVC), PaO2/FiO2, and serum protein level were significant predictors of relapse in OP patients (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.97; p=0.018; OR, 1.02; 95% CI, 1.00-1.04; p=0.042; and OR, 0.06; 95% CI, 0.01-0.87; p=0.039, respectively). Conclusion This study shows that FVC, PaO2/FiO2 and serum protein level at presentation can significantly predict relapse in OP patients. PMID:26175771

Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.

PubMed

Langhorst, Jost; Hofstetter, Anna; Wolfe, Fred; Häuser, Winfried

2013-10-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Psychological factors such as depression and stress are under debate to contribute to the risk of relapse. The impact of mucosal healing to reduce the risk of relapse had not been studied prospectively. The aim of this study was to identify whether depression and stress increase and mucosal healing reduces the risk of clinical relapse in patients with UC in clinical remission. Patients in clinical remission were followed prospectively for 1 year, or less if they relapsed. Endoscopy and histology score and long-term perceived stress (Perceived Stress Questionnaire) were measured at baseline. Mucosal healing was defined by a Mayo Endoscopy score of 0-1. Depression (Hospital Anxiety and Depression Scale) and acute perceived stress (Cohen Perceived Stress Scale) were measured at baseline and after 1, 3, 6, 9, and 12 months. A time-dependent multivariate Cox regression model determined the predictors of time to relapse. Seventy-five patients were included into final analysis, of which 28 (37.3%) relapsed. Short-term stress at the last visit before relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.10) and male gender (HR = 2.38, 95% CI = 1.01-5.61), but not baseline mucosal healing (HR = 0.86, 95% CI = 0.35-2.11), baseline long-term stress (HR = 0.20, 95% CI = 0.01-3.31), and depression at the last visit before relapse (HR = 1.08, 95% CI = 0.95-1.22) were predictive for a relapse. Short-term stress but not depression nor mucosal healing was predictive for the risk of relapse in patients with UC in clinical remission. Larger multicentre studies are necessary to confirm our findings.

PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.

PubMed

Nakhjavani, Manouchehr; Abdollahi, Soraya; Farzanefar, Saeed; Abousaidi, Mohammadtagi; Esteghamati, Alireza; Naseri, Maryam; Eftekhari, Mohamad; Abbasi, Mehrshad

2017-04-02

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement. Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic. Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3). TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal. ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

PubMed

He, Ru-Qian; Zeng, Qing-Yi; Zhu, Pan; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

2016-11-01

The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

PubMed

Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

Interrelations of Justice, Rejection, Provocation, and Moral Disgust Sensitivity and Their Links with the Hostile Attribution Bias, Trait Anger, and Aggression

PubMed Central

Bondü, Rebecca; Richter, Philipp

2016-01-01

Several personality dispositions with common features capturing sensitivities to negative social cues have recently been introduced into psychological research. To date, however, little is known about their interrelations, their conjoint effects on behavior, or their interplay with other risk factors. We asked N = 349 adults from Germany to rate their justice, rejection, moral disgust, and provocation sensitivity, hostile attribution bias, trait anger, and forms and functions of aggression. The sensitivity measures were mostly positively correlated; particularly those with an egoistic focus, such as victim justice, rejection, and provocation sensitivity, hostile attributions and trait anger as well as those with an altruistic focus, such as observer justice, perpetrator justice, and moral disgust sensitivity. The sensitivity measures had independent and differential effects on forms and functions of aggression when considered simultaneously and when controlling for hostile attributions and anger. They could not be integrated into a single factor of interpersonal sensitivity or reduced to other well-known risk factors for aggression. The sensitivity measures, therefore, require consideration in predicting and preventing aggression. PMID:27303351

[Clinical and biological prognostic factors in relapsed acute myeloid leukemia patients].

PubMed

Yébenes-Ramírez, Manuel; Serrano, Josefina; Martínez-Losada, Carmen; Sánchez-García, Joaquín

2016-09-02

Acute myeloid leukemia (AML) is the most frequent type of acute leukemia in adults. Despite recent advances in the characterization of pathogenesis of AML, the cure rates are under 40%, being leukemia relapse the most common cause of treatment failure. Leukaemia relapse occurs due to clonal evolution or clonal escape. In this study, we aimed to analyze the clinical and biological factors influencing outcomes in patients with AML relapse. We included a total of 75 AML patients who experienced leukaemia relapse after achieving complete remission. We performed complete immunophenotyping and conventional karyotyping in bone marrow aspirates obtained at diagnosis and at leukemia relapse. Overall survival (OS) of the series was 3.7%±2.3, leukaemia progression being the most common cause of death. Patients relapsing before 12 months and those with adverse cytogenetic-molecular risk had statistically significant worse outcomes. A percentage of 52.5 of patients showed phenotypic changes and 50% cytogenetic changes at relapse. We did not find significant clinical factors predicting clonal evolution. The presence of clonal evolution at relapse did not have a significant impact on outcome. Patients with relapsed AML have a dismal prognosis, especially those with early relapse and adverse cytogenetic-molecular risk. Clonal evolution with phenotypic and cytogenetic changes occurred in half of the patients without predictive clinical factors or impact on outcome. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

[Open narcissism, covered narcissism and personality disorders as predictive factors of treatment response in an out-patient Drug Addiction Unit].

PubMed

Salazar-Fraile, José; Ripoll-Alandes, Carmen; Bobes, Julio

2010-01-01

Although a high prevalence of personality disorders has been reported in substance users, the literature on their value for predicting treatment response is controversial. On the other hand, while the predictive validity of personality traits as predictors of response to drug abuse or dependence has been studied, research on the validity of narcissistic personality traits is scarce. To study the predictive value of personality disorders, narcissistic personality traits and self-esteem for predicting treatment response. We assessed 78 patients attended at an addiction treatment unit using personality disorder diagnoses and measures of self-esteem, narcissism and covert (hypersensitive) narcissism. These variables were used in a Cox survival model as predictive variables of time to relapse into drug use. Hypersensitive (covert) narcissism and borderline and passive-aggressive personality disorders were risk factors for relapse into drug use, while open narcissism was a protective factor. Self-esteem did not show predictive validity. Personality disorders characterized by impulsivity-instability and passivity-resentfulness show higher risk of relapse into drug abuse. Personality traits characterized by high sensitivity to humiliation increase the risk of relapse, whereas pride and self-confidence are protective factors.

High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study.

PubMed

Yoon, Jae-Ho; Kim, Hee-Je; Kwak, Dae-Hun; Park, Sung-Soo; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung

2017-01-23

Wilms' tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/10 4 ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001) and inferior disease free survival (62.8 vs. 91.4%, P < 0.001). Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001) and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001) were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention. Clinical Research Information Service (CRIS), KCT0002079.

Do predictors of smoking relapse change as a function of duration of abstinence? Findings from the United States, Canada, United Kingdom and Australia.

PubMed

Yong, Hua-Hie; Borland, Ron; Cummings, K Michael; Partos, Timea

2018-07-01

To estimate predictors of time to smoking relapse and test if prediction varied by quit duration. Longitudinal cohort data from the International Tobacco Control Four-Country survey with annual follow up collected between 2002 and 2015. Canada, United States, United Kingdom and Australia. A total of 9171 eligible adult smokers who had made at least one quit attempt during the study period. Time to relapse was the main outcome. Predictor variables included pre-quit baseline measures of nicotine dependence, smoking and quitting-related motivations, quitting capacity and social influence, and also two post-quit measures, use of stop-smoking medications and quit duration (1-7 days, 8-14 days, 15-31 days, 1-3 months, 3-6 months, 6-12 months, 1-2 years and 2+ years), along with socio-demographics. All factors were predictive of relapse within the first 6 months of quitting but only wanting to quit, quit intentions and number of friends who smoke were still predictive of relapse in the 6-12-month period of quitting [hazard ratios (HR) = 1.20, P < 0.05; 1.13, P < 0.05; and 1.21, P < 0.001, respectively]. Number of friends smoking was the only remaining predictor of relapse in the 1-2 years quit period (HR = 1.19, P = 0.001) with none predictive beyond the 2-year quit period. Use of stop-smoking medications during quit attempts was related negatively to relapse during the first 2 weeks of quitting (HR = 0.71-0.84), but related positively to relapse in the 1-6-month quit period (HR = 1.29-1.54). Predictive effects of all factors showed significant interaction with quit duration except for perceiving smoking as an important part of life, prematurely stubbing out a cigarette and wanting to quit. Among adult smokers in the United States, Canada, United Kingdom and Australia, factors associated with smoking relapse differ between the early and later stages of a quit attempt, suggesting that the determinants of relapse change as a function of abstinence duration. © 2018 Society for the Study of Addiction.

Characteristics predicting outcomes of allogeneic stem-cell transplantation in relapsed acute myelogenous leukemia.

PubMed

Frazer, J; Couban, S; Doucette, S; Shivakumar, S

2017-04-01

Allogeneic hematopoietic stem-cell transplantation (ahsct) is associated with significant morbidity and mortality, but it can cure carefully selected patients with acute myeloid leukemia (aml) in second remission (cr2). In a cohort of patients with aml who underwent ahsct in cr2, we determined the pre-transplant factors that predicted for overall survival (os), relapse, and non-relapse mortality. We also sought to validate the prognostic risk groups derived by Michelis and colleagues in this independent population. In a retrospective chart review, we obtained data for 55 consecutive patients who underwent ahsct for aml in cr2. Hazard ratios were used to describe the independent effects of pre-transplant variables on outcome, and Kaplan-Meier curves were used to assess outcomes in the three prognostic groups identified by Michelis and colleagues. At 1, 3, and 5 years post-transplant, os was 60%, 45.5%, and 37.5% respectively. Statistically significant differences in os, relapse mortality, and non-relapse mortality were not identified between the prognostic risk groups identified by Michelis and colleagues. Women were less likely than men to relapse, and a modified European Society for Blood and Marrow Transplantation (mebmt) score of 3 or less was associated with a lower non-relapse mortality. The 37.5% 5-year os in this cohort suggests that, compared with other options, ahsct offers patients with aml in cr2 a better chance of cure. Our study supports the use of the mebmt score to predict non-relapse mortality in this population.

SOX9 expression predicts relapse of stage II colon cancer patients.

PubMed

Marcker Espersen, Maiken Lise; Linnemann, Dorte; Christensen, Ib Jarle; Alamili, Mahdi; Troelsen, Jesper T; Høgdall, Estrid

2016-06-01

The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Relapse Risk Assessment for Schizophrenia Patients (RASP): A New Self-Report Screening Tool.

PubMed

Velligan, Dawn; Carpenter, William; Waters, Heidi C; Gerlanc, Nicole M; Legacy, Susan N; Ruetsch, Charles

2018-01-01

The Relapse Assessment for Schizophrenia Patients (RASP) was developed as a six-question self-report screener that measures indicators of Increased Anxiety and Social Isolation to assess patient stability and predict imminent relapse. This paper describes the development and psychometric characteristics of the RASP. The RASP and Positive and Negative Syndrome Scale (PANSS) were administered to patients with schizophrenia (n=166) three separate times. Chart data were collected on a subsample of patients (n=81). Psychometric analyses of RASP included tests of reliability, construct validity, and concurrent validity of items. Factors from RASP were correlated with subscales from PANSS (sensitivity to change and criterion validity [agreement between RASP and evidence of relapse]). Test-retest reliability returned modest to strong agreement at the item level and strong agreement at the questionnaire level. RASP showed good item response curves and internal consistency for the total instrument and within each of the two subscales (Increased Anxiety and Social Isolation). RASP Total Score and subscales showed good concurrent validity when correlated with PANSS Total Score, Positive, Excitement, and Anxiety subscales. RASP correctly predicted relapse in 67% of cases, with good specificity and negative predictive power and acceptable positive predictive power and sensitivity. The reliability and validity data presented support the use of RASP in settings where addition of a brief self-report assessment of relapse risk among patients with schizophrenia may be of benefit. Ease of use and scoring, and the ability to administer without clinical supervision allows for routine administration and assessment of relapse risk.

Perplexities and Provocations of Eating Disorders

ERIC Educational Resources Information Center

Halmi, Katherine A.

2009-01-01

Background: Etiological hypotheses of eating disorders, anorexia nervosa and bulimia nervosa have not produced informative research for predictably effective treatment. Methods: The rationale for applying a model of allostasis, a dysregulation of reward circuits with activation of brain and hormonal stress responses to maintain apparent stability,…

Dispositional anger and the resolution of the approach-avoidance conflict.

PubMed

Robinson, Michael D; Boyd, Ryan L; Persich, Michelle R

2016-09-01

The approach-avoidance conflict is one in which approaching reward brings increased threat while avoiding threat means forgoing reward. This conflict can be uniquely informative because it will be resolved in different ways depending on whether approach (toward) or avoidance (away from) is the stronger motive. Two studies (total N = 191) created a computerized version of this conflict and used the test to examine questions of motivational direction in anger. In Study 1, noise blast provocations increased the frequency of approach behaviors at high levels of trait anger, but decreased their frequency at low levels. In Study 2, a simpler version of the conflict test was used to predict anger in daily life. As hypothesized, greater approach frequencies in the test predicted greater anger reactivity to daily provocations and frustrations. The discussion focuses on the utility of the approach-avoidance conflict test and on questions of motivational direction in anger. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The situation specificity of youth responses to peer provocation.

PubMed

Dirks, Melanie A; Treat, Teresa A; Weersing, V Robin

2007-01-01

Previous studies have identified peer provocation as a challenging class of situations for youth. The work presented here builds on previous methods of assessing peer provocation by (a) increasing the contextual detail of the vignettes; (b) developing a reliable, descriptive coding system of the range of youth responses to physical, verbal, and relational provocation; and (c) assessing the relevance of these situations for a sample (N = 76) of ethnically diverse, economically disadvantaged youth ages 12 to 14. The vignettes were used to examine the situation specificity of youth responses to provocation. Situation and identity of aggressor were both predictors of youth responses. For example, participants "matched" physical aggression to physical provocation. These findings are consistent with previous studies demonstrating the situation specificity of social information processing, even within the relatively homogeneous category of peer provocations.

Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

PubMed Central

Malagola, Michele; Skert, Cristina; Ruggeri, Giuseppina; Ribolla, Rossella; Bernardi, Simona; Borlenghi, Erika; Pagani, Chiara; Rossi, Giuseppe; Caimi, Luigi; Russo, Domenico

2014-01-01

To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43) and at the 6th month (71% versus 20%; P = 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P = 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk. PMID:25202702

Predictors of Exercise Relapse in a College Population.

ERIC Educational Resources Information Center

Sullum, Julie; Clark, Matthew M.; King, Teresa K.

2000-01-01

Investigated factors that predicted exercise relapse among college students. Physically active undergraduates completed questionnaires measuring Prochaska's 10 processes for change of exercise, self-efficacy, and decisional balance. Exercise levels were assessed at baseline and 8 weeks later. At baseline, relapsers had significantly lower…

Longitudinal Investigation of Smoking Initiation and Relapse Among Younger and Older US Military Personnel

PubMed Central

Trone, Daniel W.; Peterson, Arthur V.; Jacobson, Isabel G.; Littman, Alyson J.; Maynard, Charles; Seelig, Amber D.; Crum-Cianflone, Nancy F.; Bricker, Jonathan B.

2015-01-01

Objectives. We examined whether military service, including deployment and combat experience, were related to smoking initiation and relapse. Methods. We included older (panel 1) and younger (panel 2) participants in the Millennium Cohort Study. Never smokers were followed for 3 to 6 years for smoking initiation, and former smokers were followed for relapse. Complementary log-log regression models estimated the relative risk (RR) of initiation and relapse by military exposure while adjusting for demographic, health, and lifestyle factors. Results. Deployment with combat experience predicted higher initiation rate (panel 1: RR = 1.44; 95% confidence interval [CI] = 1.28, 1.62; panel 2: RR = 1.26; 95% CI = 1.04, 1.54) and relapse rate (panel 1 only: RR = 1.48; 95% CI = 1.36, 1.62). Depending on the panel, previous mental health disorders, life stressors, and other military and nonmilitary characteristics independently predicted initiation and relapse. Conclusions. Deployment with combat experience and previous mental disorder may identify military service members in need of intervention to prevent smoking initiation and relapse. PMID:25880953

Impulsive suicide attempts predict post-treatment relapse in alcohol-dependent patients.

PubMed

Wojnar, Marcin; Ilgen, Mark A; Jakubczyk, Andrzej; Wnorowska, Anna; Klimkiewicz, Anna; Brower, Kirk J

2008-10-01

The present study was designed to examine the influence of suicidality on relapse in alcohol-dependent patients. Specifically, a lifetime suicide attempt at baseline was used to predict relapse in the year after treatment. Also, the unique contribution of impulsive suicide attempts was examined. A total of 154 patients with alcohol dependence, consecutively admitted to four addiction treatment facilities in Warsaw, Poland participated in the study. Of the 154 eligible patients, 118 (76.6%) completed a standardized follow-up assessment at 12 months. Previous suicide attempts were common in adults treated for alcohol dependence with 43% patients in the present sample reporting an attempt at some point during their lifetime. Additionally, more than 62% of those with a lifetime suicide attempt reported making an impulsive attempt. Lifetime suicide attempts were not associated with post-treatment relapse (chi-square=2.37, d.f.=1, p=0.124). However, impulsive suicide attempts strongly predicted relapse (OR=2.81, 95% CI=1.13-6.95, p=0.026) and time to relapse (OR=2.10, 95% CI=1.18-3.74, p=0.012) even after adjusting for other measures of baseline psychopathology, depression, impulsivity, hopelessness and alcohol use severity. This study is the first to document the relationship between pre-treatment impulsive suicide attempts and higher likelihood of post-treatment relapse in alcohol-dependent patents. Clinicians should routinely conduct an assessment for previous suicide attempts in patients with alcohol use disorders, and when impulsive suicidality is reported, they should recognize the increased risk for relapse and formulate their patients' treatment plans accordingly with the goals of reducing both alcoholic relapse and suicide rates.

Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

PubMed Central

Adinoff, Bryon; Gu, Hong; Merrick, Carmen; McHugh, Meredith; Jeon-Slaughter, Haekyung; Lu, Hanzhang; Yang, Yihong; Stein, Elliot A.

2017-01-01

BACKGROUND Cocaine-induced neuroplastic changes may result in a heightened propensity for relapse. Using regional cerebral blood flow (rCBF) as a marker of basal neuronal activity, this study assessed alterations in rCBF and related resting state functional connectivity (rsFC) to prospectively predict relapse in patients following treatment for cocaine use disorder (CUD). METHODS Pseudocontinuous arterial spin labeling functional magnetic resonance imaging and resting blood oxygen level-dependent functional magnetic resonance imaging data were acquired in the same scan session in abstinent participants with CUD before residential treatment discharge and in 20 healthy matched control subjects. Substance use was assessed twice weekly following discharge. Relapsed participants were defined as those who used stimulants within 30 days following treatment discharge (n = 22); early remission participants (n = 18) did not. RESULTS Voxel-wise, whole-brain analysis revealed enhanced rCBF only in the left posterior hippocampus (pHp) in the relapsed group compared with the early remission and control groups. Using this pHp as a seed, increased rsFC strength with the posterior cingulate cortex (PCC)/precuneus was seen in the relapsed versus early remission subgroups. Together, both increased pHp rCBF and strengthened pHp-PCC rsFC predicted relapse with 75% accuracy at 30, 60, and 90 days following treatment. CONCLUSIONS In CUD participants at risk of early relapse, increased pHp basal activity and pHp-PCC circuit strength may reflect the propensity for heightened reactivity to cocaine cues and persistent cocaine-related ruminations. Mechanisms to mute hyperactivated brain regions and delink dysregulated neural circuits may prove useful to prevent relapse in patients with CUD. PMID:25749098

Empathy Inhibits Aggression in Competition: The Role of Provocation, Emotion, and Gender.

PubMed

Stanger, Nicholas; Kavussanu, Maria; McIntyre, David; Ring, Christopher

2016-02-01

Although the empathy-aggression relationship has been well documented, research has yet to establish whether emotions mediate and gender moderates this relationship in athletes, under conditions of low and high provocation. In this experiment, we assigned team-sport athletes to either a high (n = 40) or a low (n = 40) empathy group, and asked them to compete in a reaction-time task against a (fictitious) opponent, under conditions of low and high provocation. Empathy reduced aggression (i.e., intensity of electrical shock administered to the opponent) at low provocation in men, and at both low and high provocation in women. Guilt mediated the effect of empathy on aggression at low provocation in men; anger did not mediate any effects of empathy on aggression. Our findings indicate that the inhibitory effect of empathy on aggression and the mediating role of guilt are moderated by provocation and gender.

Rates and Predictors of Renewed Quitting After Relapse During a One-Year Follow-Up Among Primary Care Patients

PubMed Central

Bold, Krysten W.; Rasheed, Abdullah S.; McCarthy, Danielle E.; Jackson, Thomas C.; Fiore, Michael C.; Baker, Timothy B.

2014-01-01

Background Most people who quit smoking relapse within a year of quitting. Little is known about what prompts renewed quitting after relapse or how often this results in abstinence. Purpose To identify rates, efficacy, and predictors of renewed quit attempts after relapse during a one-year follow-up. Methods Primary care patients in a comparative effectiveness trial of smoking cessation pharmacotherapies reported daily smoking every 6–12 weeks for 12 months to determine relapse, renewed quitting, and 12-month abstinence rates. Results Of 894 known relapsers, 291 (33%) renewed quitting for at least 24 hours and 99 (34%) of these were abstinent at follow-up. The average latency to renewed quitting was 106 days and longer latencies predicted greater success. Renewed quitting was more likely for older, male, less dependent smokers, and later abstinence was predicted by fewer depressive symptoms and longer past abstinence. Conclusions Renewed quitting is common and produces meaningful levels of cessation. PMID:24796541

Validity and Measurement

ERIC Educational Resources Information Center

Maraun, Michael D.

2012-01-01

As illuminated forcefully by Professor Newton's provocative analytical and historical excursion, as long as tests are employed to practical ends (prediction, selection, etc.) there is little cause for the metatheoretic angst that occasions rounds of papers on the topic of validity. But then, also, there seems little need, within this context of…

Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations | Office of Cancer Genomics

Cancer.gov

The majority of patients with neuroblastoma have tumors that initially respond to chemotherapy, but a large proportion will experience therapy-resistant relapses. The molecular basis of this aggressive phenotype is unknown. Whole-genome sequencing of 23 paired diagnostic and relapse neuroblastomas showed clonal evolution from the diagnostic tumor, with a median of 29 somatic mutations unique to the relapse sample. Eighteen of the 23 relapse tumors (78%) showed mutations predicted to activate the RAS-MAPK pathway.

Genotype and Phenotype Predictors of Relapse of Graves’ Disease after Antithyroid Drug Withdrawal

PubMed Central

Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

Background For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse. PMID:24783027

Genotype and phenotype predictors of relapse of graves' disease after antithyroid drug withdrawal.

PubMed

Wang, Pei-Wen; Chen, I-Ya; Juo, Suh-Hang Hank; Hsi, Edward; Liu, Rue-Tsuan; Hsieh, Ching-Jung

2013-01-01

For patients with Graves' disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. FOUR SNPS WERE SIGNIFICANTLY ASSOCIATED WITH DISEASE RELAPSE: rs231775 (OR 1.96, 95% CI 1.18-3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01-62.7), rs11569309 (OR 8.09, 95% CI 1.03-63.7), and rs3765457 (OR 2.60, 95% CI 1.08-6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09-1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05-1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15-2.35), and smoking habit (HR 1.60, 95% CI 1.05-2.42). Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.

Cognitive reactivity versus dysfunctional cognitions and the prediction of relapse in recurrent major depressive disorder.

PubMed

Figueroa, Caroline A; Ruhé, Henricus G; Koeter, Maarten W; Spinhoven, Philip; Van der Does, Willem; Bockting, Claudi L; Schene, Aart H

2015-10-01

Major depressive disorder (MDD) is a burdensome disease that has a high risk of relapse/recurrence. Cognitive reactivity appears to be a risk factor for relapse. It remains unclear, however, whether dysfunctional cognitions alone or the reactivity of such cognitions to mild states of sadness (ie, cognitive reactivity) is the crucial factor that increases relapse risk. We aimed to assess the long-term predictive value of cognitive reactivity versus dysfunctional cognitions and other risk factors for depressive relapse. In a prospective cohort of outpatients (N = 116; studied between 2000-2005) who had experienced ≥ 2 previous major depressive episodes (MDEs) and were in remission (DSM-IV) at the start of follow-up, we measured cognitive reactivity, with the Leiden Index of Depression Sensitivity (LEIDS), and dysfunctional cognitions, with the Dysfunctional Attitudes Scale, simultaneously. Course of illness (with the primary outcome of MDE assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) and time to relapse were monitored prospectively for 3.5 years. Cognitive reactivity scores were associated with time to relapse over the 3.5-year follow-up and also when corrected for the number of previous MDEs and concurrent depressive symptoms (hazard ratio for 1 standard deviation [(HR(SD)); 20 points of the LEIDS, measuring cognitive reactivity] = 1.47; 95% CI, 1.04-2.09; P = .031). Rumination appeared to be a particularly strong predictor of relapse (HR(SD) = 1.60; 95% CI, 1.13-2.26; P = .007). Dysfunctional cognitions did not predict relapse over 3.5 years (HR(SD) = 1.00; 95% CI, 0.74-1.37; P = .93). Every 20-point increase on the cognitive reactivity scale resulted in a 10% to 15% increase in risk of relapse (corrected for previous MDEs and concurrent depressive symptoms). Cognitive reactivity--and particularly rumination--is a long-term predictor of relapse. Future research should address whether psychological interventions can improve cognitive reactivity scores and thereby prevent depressive relapses. ISRCTN Identifier: 68246470. © Copyright 2015 Physicians Postgraduate Press, Inc.

Illness severity and self-efficacy as course predictors of DSM-IV alcohol dependence in a multisite clinical sample.

PubMed

Langenbucher, J; Sulesund, D; Chung, T; Morgenstern, J

1996-01-01

Illness severity and self-efficacy are two constructs of growing interest as predictors of clinical response in alcoholism. Using alternative measures of illness severity (DSM-IV symptom count, Alcohol Dependence Scale, and Addiction Severity Index) and self-efficacy (brief version of the Situational Confidence Questionnaire) rigorously controlled for theoretically important background variables, we studied their unique contribution to multiple indices of relapse, relapse latency, and use of alternative coping behaviors in a large, heterogeneous clinical sample. The Alcohol Dependence Scale contributed to the prediction of 4 of 5 relapse indicators. The SCQ failed to predict relapse behavior or its precursor, coping response. The findings emphasize the predictive validity of severity of dependence as a course specifier and underline the need for more sensitive and externally valid measures of cognitive processes such as self-efficacy for application in future studies of posttreatment behavior.

Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation.

PubMed

Sellmann, Lea; Rabe, Kim; Bünting, Ivonne; Dammann, Elke; Göhring, Gudrun; Ganser, Arnold; Stadler, Michael; Weissinger, Eva M; Hambach, Lothar

2018-05-02

Conventional analysis of host chimerism (HC) frequently fails to detect relapse before its clinical manifestation in patients with hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Quantitative PCR (qPCR)-based highly-sensitive chimerism analysis extends the detection limit of conventional (short tandem repeats-based) chimerism analysis from 1 to 0.01% host cells in whole blood. To date, the diagnostic value of highly-sensitive chimerism analysis is hardly defined. Here, we applied qPCR-based chimerism analysis to 901 blood samples of 71 out-patients with hematological malignancies after allo-SCT. Receiver operating characteristics (ROC) curves were calculated for absolute HC values and for the increments of HC before relapse. Using the best cut-offs, relapse was detected with sensitivities of 74 or 85% and specificities of 69 or 75%, respectively. Positive predictive values (PPVs) were only 12 or 18%, but the respective negative predictive values were 98 or 99%. Relapse was detected median 38 or 45 days prior to clinical diagnosis, respectively. Considering also durations of steadily increasing HC of more than 28 days improved PPVs to more than 28 or 59%, respectively. Overall, highly-sensitive chimerism analysis excludes relapses with high certainty and predicts relapses with high sensitivity and specificity more than a month prior to clinical diagnosis.

High outgroup entitativity can inhibit intergroup retribution.

PubMed

Newheiser, Anna-Kaisa; Dovidio, John F

2015-06-01

Understanding the psychological processes that are involved in the perpetuation and escalation of intergroup conflict remains an important goal for intergroup relations research. In the present research, we examined perceived outgroup entitativity as a potential determinant of intergroup hostility. In intergroup conflict situations, high-entitative outgroups are perceived as particularly deserving of retribution; however, high-entitative outgroups are also perceived as efficacious and capable of retaliating successfully, suggesting that people may inhibit hostility against high-entitative (vs. low-entitative) outgroups that are in a position to retaliate. We tested this prediction in two studies. In Study 1, we manipulated intergroup provocation and outgroup entitativity, and found that higher negative mood predicted greater aggression against a low-entitative provoker outgroup, but failed to predict aggression against a high-entitative provoker outgroup that was plausibly in a position to retaliate. In Study 2, we held provocation constant while manipulating outgroup entitativity and the possibility of retaliation by the outgroup, and found that people acted in a retributive manner against a high-entitative provoker outgroup only when the outgroup was not in a position to retaliate. Implications for intergroup conflict are discussed. © 2014 The British Psychological Society.

Predicting relapse in major depressive disorder using patient-reported outcomes of depressive symptom severity, functioning, and quality of life in the Individual Burden of Illness Index for Depression (IBI-D).

PubMed

Ishak, Waguih William; Greenberg, Jared M; Cohen, Robert M

2013-10-01

Patients with Major Depressive Disorder (MDD) often experience unexpected relapses, despite achieving remission. This study examines the utility of a single multidimensional measure that captures variance in patient-reported Depressive Symptom Severity, Functioning, and Quality of Life (QOL), in predicting MDD relapse. Complete data from remitted patients at the completion of 12 weeks of citalopram in the STAR*D study were used to calculate the Individual Burden of Illness index for Depression (IBI-D), and predict subsequent relapse at six (n=956), nine (n=778), and twelve months (n=479) using generalized linear models. Depressive Symptom Severity, Functioning, and QOL were all predictors of subsequent relapse. Using Akaike information criteria (AIC), the IBI-D provided a good model for relapse even when Depressive Symptom Severity, Functioning, and QOL were combined in a single model. Specifically, an increase of one in the IBI-D increased the odds ratio of relapse by 2.5 at 6 months (β=0.921 ± 0.194, z=4.76, p<2 × 10(-6)), by 2.84 at 9 months (β=1.045 ± 0.22, z=4.74, p<2.2 × 10(-6)), and by 4.1 at 12 months (β=1.41 ± 0.29, z=4.79, p<1.7 × 10(-6)). Self-report poses a risk to measurement precision. Using highly valid and reliable measures could mitigate this risk. The IBI-D requires time and effort for filling out the scales and index calculation. Technological solutions could help ease these burdens. The sample suffered from attrition. Separate analysis of dropouts would be helpful. Incorporating patient-reported outcomes of Functioning and QOL in addition to Depressive Symptom Severity in the IBI-D is useful in assessing the full burden of illness and in adequately predicting relapse, in MDD. © 2013 Elsevier B.V. All rights reserved.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

MicroRNA-106b~25 cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia

PubMed Central

Verboon, Lonneke J.; Obulkasim, Askar; de Rooij, Jasmijn D.E.; Katsman, Jenny E.; Sonneveld, Edwin; Baruchel, André; Trka, Jan; Reinhardt, Dirk; Pieters, Rob; Cloos, Jacqueline; Kaspers, Gertjan J.L.; Klusmann, Jan-Henning; Zwaan, Christian Michel; Fornerod, Maarten; van den Heuvel-Eibrink, Marry M.

2016-01-01

The most important reason for therapy failure in pediatric acute myeloid leukemia (AML) is relapse. In order to identify miRNAs that contribute to the clonal evolution towards relapse in pediatric AML, miRNA expression profiling of 127 de novo pediatric AML cases were used. In the diagnostic phase, no miRNA signatures could be identified that were predictive for relapse occurrence, in a large pediatric cohort, nor in a nested mixed lineage leukemia (MLL)-rearranged pediatric cohort. AML with MLL- rearrangements are found in 15-20% of all pediatric AML samples, and reveal a relapse rate up to 50% for certain translocation partner subgroups. Therefore, microRNA expression profiling of six paired initial diagnosis-relapse MLL-rearranged pediatric AML samples (test cohort) and additional eight paired initial diagnosis-relapse samples with MLL-rearrangements (validation cohort) was performed. A list of 53 differentially expressed miRNAs was identified of which the miR-106b~25 cluster, located in intron 13 of MCM7, was the most prominent. These differentially expressed miRNAs however could not predict a relapse in de novo AML samples with MLL-rearrangements at diagnosis. Furthermore, higher mRNA expression of both MCM7 and its upstream regulator E2F1 was found in relapse samples with MLL-rearrangements. In conclusion, we identified the miR-106b~25 cluster to be upregulated in relapse pediatric AML with MLL-rearrangements. PMID:27351222

Do Hostile Attribution Biases in Children and Parents Predict Relationally Aggressive Behavior?

ERIC Educational Resources Information Center

Werner, Nicole E.

2012-01-01

Relatively little is understood about the role of hostile attributions in children's use of relational aggression with peers, or about the impact of family processes on children's attributions about ambiguous provocations. This cross-sectional study investigated associations among hostile attributions made by children, mothers, and fathers, and…

Intent Attributions and Aggression: A Study of Children and Their Parents

ERIC Educational Resources Information Center

Nelson, David A.; Mitchell, Carianne; Yang, Chongming

2008-01-01

This research aimed to further clarify the relationship between children's self-reported hostile intent attributions (for ambiguous instrumental or relational provocations) and peer-reported aggression (physical and relational) in 500 fourth-grade children. In addition, we examined whether parents' intent attributions might predict children's…

Relapse and Recurrence Prevention in the Treatment for Adolescents with Depression Study

ERIC Educational Resources Information Center

Simons, Anne D.; Rohde, Paul; Kennard, Betsy D.; Robins, Michele

2005-01-01

Relapse and recurrence in adolescent depression are important problems. Much less is known about relapse prevention compared to the acute treatment of depression in adolescents. Based on previous research, theoretical predictions, and clinical experience, the Treatment for Adolescents With Depression Study (TADS) protocol was designed to determine…

Neural response in obsessive-compulsive washers depends on individual fit of triggers

PubMed Central

Baioui, Ali; Pilgramm, Juliane; Merz, Christian J.; Walter, Bertram; Vaitl, Dieter; Stark, Rudolf

2013-01-01

Background: Patients with obsessive-compulsive disorder (OCD) have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods. This functional magnetic resonance imaging (fMRI) study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. Methods: Nineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. Results: OCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum) for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation. Conclusions: The present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation. PMID:23630478

Reliability and validity of three pain provocation tests used for the diagnosis of chronic proximal hamstring tendinopathy.

PubMed

Cacchio, Angelo; Borra, Fabrizio; Severini, Gabriele; Foglia, Andrea; Musarra, Frank; Taddio, Nicola; De Paulis, Fosco

2012-09-01

The clinical assessment of chronic proximal hamstring tendinopathy (PHT) in athletes is a challenge to sports medicine. To be able to compare the results of research and treatments, the methods used to diagnose and evaluate PHT must be clearly defined and reproducible. To assess the reliability and validity of three pain provocation tests used for the diagnosis of PHT. Ninety-two athletes with (N=46) and without (N=46) PHT were examined by one physician and two physiotherapists, who were trained in the examination techniques before the study. The examiners were blinded to the symptoms and identity of the athletes. The three pain provocation tests examined were the Puranen-Orava, bent-knee stretch and modified bent-knee stretch tests. Intraclass correlation coefficients (ICCs) based on the repeated measures analysis of variance were used to analyse the intraexaminer and interexaminer reliability, while sensitivity, specificity, predictive values and likelihood ratios were used to determine the validity of the three tests. The ICC values in all three tests revealed a high correlation (range 0.82 to 0.88) for the interexaminer reliability and a high-to-very high correlation (range 0.87 to 0.93) for the intraexaminer reliability. All three tests displayed a moderate-to-high validity, with the highest degree of validity being yielded by the modified bent-knee stretch test. All three pain provocation tests proved to be of potential value in assessing chronic PHT in athletes. However, we recommend that they be used in conjunction with other objective measures, such as MRI.

Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PubMed

Hemmati, Philipp G; Vuong, Lam G; Terwey, Theis H; Jehn, Christian F; le Coutre, Philipp; Penack, Olaf; Na, Il-Kang; Dörken, Bernd; Arnold, Renate

2017-02-01

The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

48-Week Outcome after Cessation of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patient and the Associated Factors with Relapse.

PubMed

Xu, Wen-Xiong; Zhang, Qian; Zhu, Xiang; Lin, Chao-Shuang; Chen, You-Ming; Deng, Hong; Mei, Yong-Yu; Zhao, Zhi-Xin; Xie, Dong-Ying; Gao, Zhi-Liang; Xie, Chan; Peng, Liang

2018-01-01

We aimed to ascertain the feasibility and safety of NA cessation, the status of patients after cessation, and the predictive factors for relapse and subsequent retreatment. A total of 92 patients were enrolled in this prospective study. Patients were monitored every month for the first 3 months after cessation and every 3 months thereafter. Sixty-two patients finished 48 weeks of follow-up. None died or developed liver failure, cirrhosis, or HCC. The 62 patients could be divided into 4 categories according to the 48-week clinical development of relapse. Virologic relapses occurred in 39 (62.9%) patients, with 72.7% occurring in the first 24 weeks in origin HBeAg positive patients and 82.4% in the first 12 weeks in origin HBeAg negative patients. Age (OR = 1.06, 95% CI = 1.02-1.10; p = 0.003), the HBsAg level (OR = 2.21, 95% CI = 1.47-3.32; p < 0.001), and positive origin HBeAg status (OR = 0.32, 95% CI = 0.14-0.74; p = 0.008) were predictive factors to virologic relapse. HBV DNA level (OR = 1.34, 95% CI = 1.13-1.58; p < 0.001) was predictive factor to retreatment. NA cessation is safe under supervision. Age, HBsAg level, and origin HBeAg status can be predictive factors for virologic relapse. The study was submitted to ClinicalTrials.gov Protocol Registration and Results System with the assigned NCT ID NCT02883647.

The motivation to stay abstinent in ex-smokers: comparing the present with the past.

PubMed

Dijkstra, Arie; Borland, Ron; Buunk, Bram P

2007-10-01

Little is known about the motivation of ex-smokers to stay abstinent. In the present study we argue that ex-smokers compare their present to their past when they still smoked to conclude whether they make good progress towards a satisfactory state of continued abstinence. These temporal comparisons are thought to be central in the motivation to stay abstinent in ex-smokers. The power of temporal comparisons to predict relapse was tested in two related samples of ex-smokers (N=152 and N=197), together with two other relevant psychological factors; positive outcome expectations of smoking and self-efficacy expectations. In the first sample of ex-smokers, only temporal comparisons predicted relapse after 2 months. In the second sample of ex-smokers, temporal comparisons mediated the relation between perceived positive outcomes of smoking and relapse after 6 months. In addition, in predicting relapse after 6 months, temporal comparisons interacted with self-efficacy. The present study suggests that temporal comparisons comprise the cognitive aspect of the motivation of ex-smokers to stay abstinent. This conceptualization of the motivation in ex-smokers can be used in practice to prevent relapse.

Gender differences in alcohol and substance use relapse.

PubMed

Walitzer, Kimberly S; Dearing, Ronda L

2006-03-01

This review explores gender differences in relapse and characteristics of relapse events in alcohol and substance use. For alcohol, relapse rates were similar across gender. Although negative mood, childhood sexual abuse, alcohol-related self-efficacy, and poorer coping strategies predicted alcohol relapse, gender did not moderate these effects. Gender did moderate the association between marriage and alcohol relapse. For women, marriage and marital stress were risk factors for alcohol relapse; among men, marriage lowered relapse risk. This gender difference in the role of marriage in relapse may be a result of partner differences in problem drinking. Alcoholic women are more likely to be married to heavy drinking partners than are alcoholic men; thus, alcoholic women may be put at risk of relapse by marriage and alcoholic men may be protected by marriage. There are fewer studies documenting gender differences in substance abuse relapse so conclusions are limited and tentative. In contrast to the lack of gender differences in alcohol relapse rates, women appear less likely to experience relapse to substance use, relative to men. Women relapsing to substance use appear to be more sensitive to negative affect and interpersonal problems. Men, in contrast, may be more likely to have positive experiences prior to relapse.

Risk factors for relapse to problem drinking among current and former US military personnel: a prospective study of the Millennium Cohort.

PubMed

Williams, Emily C; Frasco, Melissa A; Jacobson, Isabel G; Maynard, Charles; Littman, Alyson J; Seelig, Amber D; Crum-Cianflone, Nancy F; Nagel, Anna; Boyko, Edward J

2015-03-01

Military service members may be prone to relapse to problem drinking after remission, given a culture of alcohol use as a coping mechanism for stressful or traumatic events associated with military duties or exposures. However, the prevalence and correlates of relapse are unknown. We sought to identify socio-demographic, military, behavioral, and health characteristics associated with relapse among current and former military members with remittent problem drinking. Participants in the longitudinal Millennium Cohort Study who reported problem drinking at baseline (2001-2003) and were remittent at first follow-up (2004-2006) were included (n=6909). Logistic regression models identified demographic, military service, behavioral, and health characteristics that predicted relapse (report of ≥1 past-year alcohol-related problem on the validated Patient Health Questionnaire) at the second follow-up (2007-2008). Sixteen percent of those with remittent problem drinking relapsed. Reserve/National Guard members compared with active-duty members (odds ratio [OR]=1.71, 95% confidence interval [CI]: 1.45-2.01), members separated from the military during follow-up (OR=1.46, 95% CI: 1.16-1.83), and deployers who reported combat exposure (OR=1.32, 95% CI: 1.07-1.62, relative to non-deployers) were significantly more likely to relapse. Those with multiple deployments were significantly less likely to relapse (OR=0.73, 95% CI: 0.58-0.92). Behavioral factors and mental health conditions also predicted relapse. Relapse was common and associated with military and non-military factors. Targeted intervention to prevent relapse may be indicated for military personnel in particular subgroups, such as Reservists, veterans, and those who deploy with combat exposure. Copyright © 2015. Published by Elsevier Ireland Ltd.

Manual unloading of the lumbar spine: can it identify immediate responders to mechanical traction in a low back pain population? A study of reliability and criterion referenced predictive validity

PubMed Central

Swanson, Brian T.; Riley, Sean P.; Cote, Mark P.; Leger, Robin R.; Moss, Isaac L.; Carlos,, John

2016-01-01

Background To date, no research has examined the reliability or predictive validity of manual unloading tests of the lumbar spine to identify potential responders to lumbar mechanical traction. Purpose To determine: (1) the intra and inter-rater reliability of a manual unloading test of the lumbar spine and (2) the criterion referenced predictive validity for the manual unloading test. Methods Ten volunteers with low back pain (LBP) underwent a manual unloading test to establish reliability. In a separate procedure, 30 consecutive patients with LBP (age 50·86±11·51) were assessed for pain in their most provocative standing position (visual analog scale (VAS) 49·53±25·52 mm). Patients were assessed with a manual unloading test in their most provocative position followed by a single application of intermittent mechanical traction. Post traction, pain in the provocative position was reassessed and utilized as the outcome criterion. Results The test of unloading demonstrated substantial intra and inter-rater reliability K = 1·00, P = 0·002, K = 0·737, P = 0·001, respectively. There were statistically significant within group differences for pain response following traction for patients with a positive manual unloading test (P<0·001), while patients with a negative manual unloading test did not demonstrate a statistically significant change (P>0·05). There were significant between group differences for proportion of responders to traction based on manual unloading response (P = 0·031), and manual unloading response demonstrated a moderate to strong relationship with traction response Phi = 0·443, P = 0·015. Discussion and conclusion The manual unloading test appears to be a reliable test and has a moderate to strong correlation with pain relief that exceeds minimal clinically important difference (MCID) following traction supporting the validity of this test. PMID:27559274

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

PubMed Central

Levandovsky, Mark; Harvey, Danielle; Lara, Primo; Wun, Ted

2008-01-01

Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. Results Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. Conclusion Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder. PMID:19046460

Bite by a dog under provocation: is it free from risk?

PubMed

Dutta, J K

2002-05-01

There is a common belief that rabid dogs bite without provocation, hence a dog bite under provocation is free from the risk of rabies. This is not always true as is evident from the case report narrated below. Here in this article, a man of 38 years was bitten by a dog under provocation. He developed rabies 4 months after the bite and subsequently died. Autopsy revealed Negri bodies from the brain tissue.

CA-125 AUC as a predictor for epithelial ovarian cancer relapse.

PubMed

Mano, António; Falcão, Amílcar; Godinho, Isabel; Santos, Jorge; Leitão, Fátima; de Oliveira, Carlos; Caramona, Margarida

2008-01-01

The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse. Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity. In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days. Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

The Alcohol Relapse Risk Assessment: a scoring system to predict the risk of relapse to any alcohol use after liver transplant.

PubMed

Rodrigue, James R; Hanto, Douglas W; Curry, Michael P

2013-12-01

Alcohol relapse after liver transplant heightens concern about recurrent disease, nonadherence to the immunosuppression regimen, and death. To develop a scoring system to stratify risk of alcohol relapse after liver transplant. Retrospective medical record review. All adult liver transplants performed from May 2002 to February 2011 at a single center in the United States. The incidence of return to any alcohol consumption after liver transplant. Thirty-four percent (40/118) of patients with a history of alcohol abuse/dependency relapsed to use of any alcohol after liver transplant. Nine of 25 hypothesized risk factors were predictive of alcohol relapse after liver transplant: absence of hepatocellular carcinoma, tobacco dependence, continued alcohol use after liver disease diagnosis, low motivation for alcohol treatment, poor stress management skills, no rehabilitation relationship, limited social support, lack of nonmedical behavioral consequences, and continued engagement in social activities with alcohol present. Each independent predictor was assigned an Alcohol Relapse Risk Assessment (ARRA) risk value of 1 point, and patients were classified into 1 of 4 groups by ARRA score: ARRA I = 0, ARRA II = 1 to 3, ARRA III = 4 to 6, and ARRA IV = 7 to 9. Patients in the 2 higher ARRA classifications had significantly higher rates of alcohol relapse and were more likely to return to pretransplant levels of drinking. Alcohol relapse rates are moderately high after liver transplant. The ARRA is a valid and practical tool for identifying pretransplant patients with alcohol abuse or dependency at elevated risk of any alcohol use after liver transplant.

Gender differences in the effect of visual sexual stimulation on the perceived covariation between freedom and responsibility.

PubMed

Nevala, James D; Gray, Nicholas J; McGahan, Joseph R; Minchew, Teresa

2006-03-01

The authors replicated and extended a test of Epstein's cognitive-experiential self-theory (CEST; S. Epstein, 1973, 1980, 1985, 1994, 2003) regarding subjective estimates of the relationship between freedom and responsibility. CEST predicts that information in the form of sexually provocative images is likely to be processed by the experiential system. The authors' hypothesis was that such experiential processing would cause an increase in the likelihood of participants endorsing as true a statement that proposed a negative correlation between freedom and responsibility. University students (N = 97) in introductory psychology classes viewed 25 images of either men or women in provocative clothing, or a control consisting of academic journal covers, after which they responded to 24 statements proposing either a positive, negative, or noncontingent relationship between freedom and responsibility. Judgments were analyzed according to perceiver gender and target gender, as well as the framing of the proposition and its contingency category. The hypothesis was supported for the men and to a lesser extent for the women. Although priming the experiential system by exposing participants to sexually provocative images did not change endorsement rates of positive contingencies, it did lead to an increase in the likelihood of simultaneously endorsing negative contingencies.

Scopolamine provocation-based pharmacological MRI model for testing procognitive agents.

PubMed

Hegedűs, Nikolett; Laszy, Judit; Gyertyán, István; Kocsis, Pál; Gajári, Dávid; Dávid, Szabolcs; Deli, Levente; Pozsgay, Zsófia; Tihanyi, Károly

2015-04-01

There is a huge unmet need to understand and treat pathological cognitive impairment. The development of disease modifying cognitive enhancers is hindered by the lack of correct pathomechanism and suitable animal models. Most animal models to study cognition and pathology do not fulfil either the predictive validity, face validity or construct validity criteria, and also outcome measures greatly differ from those of human trials. Fortunately, some pharmacological agents such as scopolamine evoke similar effects on cognition and cerebral circulation in rodents and humans and functional MRI enables us to compare cognitive agents directly in different species. In this paper we report the validation of a scopolamine based rodent pharmacological MRI provocation model. The effects of deemed procognitive agents (donepezil, vinpocetine, piracetam, alpha 7 selective cholinergic compounds EVP-6124, PNU-120596) were compared on the blood-oxygen-level dependent responses and also linked to rodent cognitive models. These drugs revealed significant effect on scopolamine induced blood-oxygen-level dependent change except for piracetam. In the water labyrinth test only PNU-120596 did not show a significant effect. This provocational model is suitable for testing procognitive compounds. These functional MR imaging experiments can be paralleled with human studies, which may help reduce the number of false cognitive clinical trials. © The Author(s) 2015.

Provocative questions in cancer epidemiology in a time of scientific innovation and budgetary constraints.

PubMed

Lam, Tram Kim; Schully, Sheri D; Rogers, Scott D; Benkeser, Rachel; Reid, Britt; Khoury, Muin J

2013-04-01

In a time of scientific and technological developments and budgetary constraints, the National Cancer Institute's (NCI) Provocative Questions Project offers a novel funding mechanism for cancer epidemiologists. We reviewed the purposes underlying the Provocative Questions Project, present information on the contributions of epidemiologic research to the current Provocative Questions portfolio, and outline opportunities that the cancer epidemiology community might capitalize on to advance a research agenda that spans a translational continuum from scientific discoveries to population health impact.

Stress-related increases in risk taking and attentional failures predict earlier relapse to smoking in young adults: A pilot investigation.

PubMed

Schepis, Ty S; Tapscott, Brian E; Krishnan-Sarin, Suchitra

2016-04-01

Substantial evidence links greater impulsivity and stress exposure to poorer smoking cessation outcomes. Results from adolescents also indicate that stress-related change in risk taking can impede cessation attempts. We investigated the effects of stress-related change in impulsivity, risk taking, attention and nicotine withdrawal, and craving in young adult smokers on time to smoking relapse in a relapse analogue paradigm. Twenty-six young adult smokers (50% women; mean age: 20.9 ± 1.8) were exposed to a stress imagery session followed by a contingency management-based relapse analogue paradigm. Participants smoked at least 5 cigarettes daily, with a mean baseline carbon monoxide (CO) level of 13.7 (± 5.1) ppm. Repeated measures analysis of variance (ANOVA) and paired t tests examined stress induction validity and Cox regressions of proportional hazards examined the effects of stress-related changes in nicotine withdrawal, nicotine craving, attention, impulsivity, and risk taking on time to relapse. While stress-related change in impulsivity, nicotine craving and withdrawal did not predict time to relapse (all ps > .10), greater stress-related increases in reaction time (RT) variability (p = .02) were predictive of shorter time to relapse, with trend-level findings for inattention and risk taking. Furthermore, changes in stress-related risk taking affected outcome in women more than in men, with a significant relationship between stress-related change in risk taking only in women (p = .026). Smoking cessation attempts in young adults may be adversely impacted by stress-related increases in risk taking and attentional disruption. Clinicians working with young adults attempting cessation may need to target these stress-related impairments by fostering more adaptive coping and resilience. (c) 2016 APA, all rights reserved).

Psychological and environmental determinants of relapse in crack cocaine smokers.

PubMed

Wallace, B C

1989-01-01

The paper reviews approaches to relapse in the treatment of cocaine abusers. Approaches reveal a common mechanism underlying relapse that involves drug craving, recall of euphoria, environmental cues, denial, myths of being able to sell or use drugs, and painful affect states necessitating use of a multifaceted clinical technique. Empirical validation of a common mechanism underlying relapse establishes a typology of psychological and environmental determinants of relapse for crack cocaine smokers (N = 35) who relapse after hospital detoxification and return a second time. Major findings are that relapse follows a painful emotional state (40%), failure to enter arranged aftercare treatment (37%), or encounters with conditioned environmental stimuli (34%), and involves narcissistic psychopathology and denial (28.5%) and interpersonal stress (24%); 85.7% involve multideterminants. Case examples illustrate the role of multideterminants in relapse. The paper educates clinicians to the integrated theory and multifaceted clinical technique necessary for efficacious treatment of cocaine patients, while the typology predicts probable relapse situations.

Distilled water nasal provocation in hyperreactive patients.

PubMed

Baudoin, T; Anzic, S A; Kalogjera, L

1999-01-01

Nonisotonic aerosol may act as a provocation agent in the upper and lower airways of hyperreactive individuals. The purpose of the study was to compare the results of nasal challenge with distilled water in patients with allergic rhinitis to those with noninfective nonallergic rhinitis (NINAR), with respect to the potential clinical use of the obtained data. A group of 68 ambulatory patients with allergic rhinitis or NINAR (39 perennial allergic, 6 seasonal, 23 NINAR) were challenged with 10 mL of distilled water aerosol after the baseline active anterior rhinomanometry. Patients with nasal polyposis at endoscopy, significant unilateral septal deviation, positive bacteriologic swab, recent nasal surgery, and uncertain anamnestic data about the medication taken 6 weeks before the provocation were excluded from the study. After 10 minutes of nasal provocation, rhinomanometry was repeated to assess the response. In 15 patients of the perennial allergic group, the same measurements were performed after a 2-week oral antihistamine and topical steroid therapy. Nasal resistance was significantly increased on the more patent side of the nose after nasal provocation with distilled water aerosol in allergic patients in comparison to the nasal resistance before provocation. In the patients with NINAR, the provocation resulted in a significant rise on the more patent side, but the total nasal airway resistance (NAR) levels were also significantly increased. The systemic antihistamine and topical steroid 2-week therapy in patients with perennial allergic rhinitis significantly reduced the response to nasal distilled water provocation. Nasal provocation with distilled water aerosol is a cheap, simple, and acceptable method that provides useful clinical data on the level of nonspecific nasal hyperreactivity and the therapy success.

Monitoring of minimal residual disease after allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia allows for the identification of impending relapse: results of the ALL-BFM-SCT 2003 trial.

PubMed

Bader, Peter; Kreyenberg, Hermann; von Stackelberg, Arend; Eckert, Cornelia; Salzmann-Manrique, Emilia; Meisel, Roland; Poetschger, Ulrike; Stachel, Daniel; Schrappe, Martin; Alten, Julia; Schrauder, Andre; Schulz, Ansgar; Lang, Peter; Müller, Ingo; Albert, Michael H; Willasch, Andre M; Klingebiel, Thomas E; Peters, Christina

2015-04-10

To elucidate the impact of minimal residual disease (MRD) after allogeneic transplantation, the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster Stem Cell Transplantation Group (ALL-BFM-SCT) conducted a prospective clinical trial. In the ALL-BFM-SCT 2003 trial, MRD was assessed in the bone marrow at days +30, +60, +90, +180, and +365 after transplantation in 113 patients with relapsed disease. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD Group. All patients showed a 3-year probability of event-free survival (pEFS) of 55%. The cumulative incidence rates of relapse and treatment-related mortality were 32% and 12%, respectively. The pEFS was 60% for patients who received their transplantations in second complete remission, 50% for patients in ≥ third complete remission, and 0% for patients not in remission (P = .015). At all time points, the level of MRD was inversely correlated with event-free survival (EFS; P < .004) and positively correlated with the cumulative incidence of relapse (P < .01). A multivariable Cox model was fitted for each time point, which showed that MRD ≥ 10(-4) leukemic cells was consistently correlated with inferior EFS (P < .003). The accuracy of MRD measurements in predicting relapse was investigated with time-dependent receiver operating curves at days +30, +60, +90, and +180. From day +60 onward, the discriminatory power of MRD detection to predict the probability of relapse after 1, 3, 6, and 9 months was more than 96%, more than 87%, more than 71%, and more than 61%, respectively. MRD after transplantation was a reliable marker for predicting impending relapses and could thus serve as the basis for pre-emptive therapy. © 2015 by American Society of Clinical Oncology.

Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics.

PubMed

Vezir, Emine; Dibek Misirlioglu, Emine; Civelek, Ersoy; Capanoglu, Murat; Guvenir, Hakan; Ginis, Tayfur; Toyran, Muge; Kocabas, Can N

2016-02-01

Skin testing has a limited role in the diagnosis of non-immediate beta-lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. Oral provocation tests with suspected antibiotics were performed to patients with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. Skin tests were not performed before provocation tests. A total of five doses were administered with half-an-hour intervals in increasing doses. Provocation was continued for 5 days. A total of 119 patients with a median age of 4.3 (IQR: 2-7.5) years, of whom 58% were males, were included in the study. Amoxicillin-clavulanic acid was the most frequently responsible agent in 87 (73.1%) patients, and most common type of rash was maculopapular in 74 (62.2%) patients. Four patients (3.4%) had an urticarial reaction during the provocation test. We did not experience any severe reactions during oral provocation test without previous skin tests performed to children with non-immediate mild cutaneous reactions without systemic symptoms. Omitting skin tests before oral provocation test in this group of children can help decreasing the burden of allergy clinics and alleviating the discomfort of children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Performance evaluation of 4 measuring methods of ground-glass opacities for predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer: a multicenter study.

PubMed

Kakinuma, Ryutaro; Kodama, Ken; Yamada, Kouzo; Yokoyama, Akira; Adachi, Shuji; Mori, Kiyoshi; Fukuyama, Yasuro; Fukuda, Yasuro; Kuriyama, Keiko; Oda, Junichi; Oda, Junji; Noguchi, Masayuki; Matsuno, Yoshihiro; Yokose, Tomoyuki; Ohmatsu, Hironobu; Nishiwaki, Yutaka

2008-01-01

To evaluate the performance of 4 methods of measuring the extent of ground-glass opacities as a means of predicting the 5-year relapse-free survival of patients with peripheral nonsmall cell lung cancer (NSLC). Ground-glass opacities on thin-section computed tomographic images of 120 peripheral NSLCs were measured at 7 medical institutions by the length, area, modified length, and vanishing ratio (VR) methods. The performance (Az) of each method in predicting the 5-year relapse-free survival was evaluated using receiver operating characteristic analysis. The mean Az value obtained by the length, area, modified length, and VR methods in the receiver operating characteristic analyses was 0.683, 0.702, 0.728, and 0.784, respectively. The differences between the mean Az value obtained by the VR method and by the other 3 methods were significant. Vanishing ratio method was the most accurate predictor of the 5-year relapse-free survival of patients with peripheral NSLC.

Delay of smoking gratification as a laboratory model of relapse: effects of incentives for not smoking, and relationship with measures of executive function.

PubMed

Mueller, Eldon T; Landes, Reid D; Kowal, Benjamin P; Yi, Richard; Stitzer, Maxine L; Burnett, Cody A; Bickel, Warren K

2009-09-01

Nineteen nicotine-deprived cigarette smokers received monetary rewards for each minute they chose not to initiate smoking in 2-h laboratory sessions followed by a 30-min period of enforced abstinence from smoking. Reinforcer amounts were delivered according to one of three schedules: increasing, decreasing, and constant. Relapse time (time until first cigarette) was shortest in the decreasing condition, longest in the increasing condition, and intermediate in the constant condition. All differences were significant except in the constant-decreasing comparison. The relationships between a battery of baseline assessments and relapse times were examined. Relapse times were predicted by delay-discounting coefficients (k) for $10 and $1000 in money and for $1000 of cigarettes. Relapse times were also predicted by the number of cigarettes smoked daily and a Wisconsin Card Sorting Test score. Performance on the Stroop Task and the Fagerström Test for Nicotine Dependence differentiated participants dichotomized into those who relapsed 'earlier' in sessions versus those who first smoked 'later'. The variability in some scores from smoking-urges and affect questionnaires administered after smoking-room sessions was explained by measures related to in-session nicotine intake. Results are discussed as they relate to contingency-management procedures, predictors of relapse, and the competing neurobehavioral decision systems theory of addiction.

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses

PubMed Central

Petkau, J; Reingold, SC; Held, U; Cutter, GR; Fleming, TR; Hughes, MD; Miller, DH; McFarland, HF; Wolinsky, JS

2009-01-01

Background Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. Objective The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. Methods We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. Results Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. Conclusions Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy. PMID:18535021

Delay of Smoking Gratification as a Laboratory Model of Relapse: Effects of Incentives for Not Smoking, and Relationship to Measures of Executive Function

PubMed Central

Mueller, E. Terry; Landes, Reid D.; Kowal, Benjamin P.; Yi, Richard; Stitzer, Maxine L.; Burnett, Cody A.; Bickel, Warren K.

2010-01-01

Nineteen nicotine-deprived cigarette smokers received monetary rewards for each minute they choose not to initiate smoking in 2-hour laboratory sessions followed by a 30-min period of enforced abstinence from smoking. Reinforcer amounts were delivered according to one of three schedules: increasing, decreasing, and constant. Relapse time (time until first smoke) was shortest in the decreasing condition, longest in the increasing condition, and intermediate in the constant condition. All differences were significant except in the constant-decreasing comparison. The relationships between a battery of baseline assessments and relapse times were examined. Relapse times were predicted by delay-discounting coefficients (k) for $10 and $1000 in money, and for $1000 of cigarettes. Relapse times were also predicted by the number of cigarettes smoked daily and a Wisconsin Card Sorting Test score. Performance on the Stroop Task and the Fagerström Test for Nicotine Dependence differentiated participants dichotomized into those who relapsed “earlier” in sessions versus those who first smoked “later.” Variability on some scores from smoking-urges and affect questionnaires administered after smoking-room sessions was explained by measures related to in-session nicotine intake. Results are discussed as they relate to contingency-management procedures, predictors of relapse, and the competing neuro-behavioral decision systems theory of addiction. PMID:19741301

Stressful Life Events Predict Eating Disorder Relapse Following Remission: Six-Year Prospective Outcomes

PubMed Central

Grilo, Carlos M.; Pagano, Maria E.; Stout, Robert L.; Markowitz, John C.; Ansell, Emily B.; Pinto, Anthony; Zanarini, Mary C.; Yen, Shirley; Skodol, Andrew E.

2012-01-01

Objective To examine prospectively the natural course of bulimia nervosa (BN) and eating disorder not-otherwise-specified (EDNOS) and test for the effects of stressful life events (SLE) on relapse after remission from these eating disorders. Method 117 female patients with BN (N = 35) or EDNOS (N = 82) were prospectively followed for 72 months using structured interviews performed at baseline, 6- and 12-months, and then yearly thereafter. ED were assessed with the structured clinical interview for DSM-IV, and monitored over time with the longitudinal interval follow-up evaluation. Personality disorders were assessed with the diagnostic interview for DSM-IV-personality-disorders, and monitored over time with the follow-along-version. The occurrence and specific timing of SLE were assessed with the life events assessment interview. Cox proportional-hazard-regression-analyses tested associations between time-varying levels of SLE and ED relapse, controlling for comorbid psychiatric disorders, ED duration, and time-varying personality-disorder status. Results ED relapse probability was 43%; BN and EDNOS did not differ in time to relapse. Negative SLE significantly predicted ED relapse; elevated work and social stressors were significant predictors. Psychiatric comorbidity, ED duration, and time-varying personality-disorder status were not significant predictors. Discussion Higher work and social stress represent significant warning signs for triggering relapse for women with remitted BN and EDNOS. PMID:21448971

Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.

PubMed

Sinha, Rajita; Fox, Helen C; Hong, Kwang-Ik Adam; Hansen, Julie; Tuit, Keri; Kreek, Mary Jeanne

2011-09-01

Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Inpatient treatment in a community mental health center and hospital-based research unit. Treatment-engaged alcohol-dependent individuals and healthy controls. Time to alcohol relapse and to heavy drinking relapse. Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

Predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients successfully treated with methotrexate alone.

PubMed

Couder, Florence; Massardier, Jérôme; You, Benoît; Abbas, Fatima; Hajri, Touria; Lotz, Jean-Pierre; Schott, Anne-Marie; Golfier, François

2016-07-01

Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3.

PubMed

Frega, Antonio; Sesti, Francesco; Lombardi, Danila; Votano, Sergio; Sopracordevole, Francesco; Catalano, Angelica; Milazzo, Giusi Natalia; Lombardo, Riccardo; Assorgi, Chiara; Olivola, Sara; Chiusuri, Valentina; Ricciardi, Enzo; French, Deborah; Moscarini, Massimo

2014-05-01

The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse. The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3. Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease. The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse. HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up. Copyright © 2014 Elsevier B.V. All rights reserved.

Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

PubMed

van Griensven, Johan; Mengesha, Bewketu; Mekonnen, Tigist; Fikre, Helina; Takele, Yegnasew; Adem, Emebet; Mohammed, Rezika; Ritmeijer, Koert; Vogt, Florian; Adriaensen, Wim; Diro, Ermias

2018-01-01

Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; P : 0.03]. Conclusion: A simple field-deployable Leishmania urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.

Myelography and cytology in the treatment of medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deutsch, M.; Reigel, D.H.

1981-06-01

Eight of 22 children with newly diagnosed medulloblastoma had asymptomatic spinal cord involvement detected by myelography. Two additional patients had demonstrable spinal cord lesions at the time of relapse in the posterior fossa. Cerebral spinal fluid (CSF) cytology results were inaccurate in predicting cord involvement. Seven patients have relapsed 9 to 69 months from completion of radiotherapy. Three had initial cord involvement and also had subsequent cord involvement at the time of intracranial relapse or afterwards. Frontal lobe involvement as the initial site of relapse occurred in 3 patients. Computerized tomography has been valuable in the early detection of intracranialmore » relapse. Three children are alive and well 10, 18 and 19 months, respectively, from time of relapse. All were retreated with radiotherapy in conjunction with misonidazole and subsequent chemotherapy.« less

Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse

DTIC Science & Technology

2017-07-01

disease function by Ingenuity Pathway Analysis (IPA). The 239 genes involved in dormancy showed a z-score increase in disease states related to acute ...genes shared by both week 6 groups, one relapsing and the other dormant, showed predicted activation of both chronic and acute disease states. In...genes among 239 shared probe sets involved in maintenance of dormancy shows predicted activation of disease states related to acute inflammation, 682

American cutaneous leishmaniasis: use of a skin test as a predictor of relapse after treatment.

PubMed Central

Passos, V. M.; Barreto, S. M.; Romanha, A. J.; Krettli, A. U.; Volpini, A. C.; Lima e Costa, M. F.

2000-01-01

While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%). No association was found between these relapses and the parasite-specific antibody response before and after treatment, or between the relapses and stratification by sociodemographic and clinical characteristics. However when Leishmania was used as antigen, patients with a negative skin test at the time of diagnosis presented a 3.4-fold higher risk (hazard risk = 3.4; 95% confidence interval, 1.7-7.0) of American cutaneous leishmaniasis relapse, compared with patients with a positive response. This result shows that the skin test can be a predictor of American cutaneous leishmaniasis relapse after treatment. PMID:10994280

Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa: A Functional Neuroimaging Study

PubMed Central

Giampietro, Vincent; Uher, Rudolf; Mataix-Cols, David; Brammer, Michael J.; Williams, Steven C. R.; Treasure, Janet; Campbell, Iain C.

2014-01-01

Anorexia nervosa (AN), obsessive–compulsive disorder (OCD), and obsessive–compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of ‘ordering’ symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN. PMID:24844926

Provocation of symmetry/ordering symptoms in Anorexia nervosa: a functional neuroimaging study.

PubMed

Suda, Masashi; Brooks, Samantha J; Giampietro, Vincent; Uher, Rudolf; Mataix-Cols, David; Brammer, Michael J; Williams, Steven C R; Treasure, Janet; Campbell, Iain C

2014-01-01

Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.

Pavlovian-to-instrumental transfer effects in the nucleus accumbens relate to relapse in alcohol dependence.

PubMed

Garbusow, Maria; Schad, Daniel J; Sebold, Miriam; Friedel, Eva; Bernhardt, Nadine; Koch, Stefan P; Steinacher, Bruno; Kathmann, Norbert; Geurts, Dirk E M; Sommer, Christian; Müller, Dirk K; Nebe, Stephan; Paul, Sören; Wittchen, Hans-Ulrich; Zimmermann, Ulrich S; Walter, Henrik; Smolka, Michael N; Sterzer, Philipp; Rapp, Michael A; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas

2016-05-01

In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. © 2015 Society for the Study of Addiction.

Clinical predictors for the prognosis of myasthenia gravis.

PubMed

Wang, Lili; Zhang, Yun; He, Maolin

2017-04-19

Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.

Implicit attitudes towards smoking predict long-term relapse in abstinent smokers.

PubMed

Spruyt, Adriaan; Lemaigre, Valentine; Salhi, Bihiyga; Van Gucht, Dinska; Tibboel, Helen; Van Bockstaele, Bram; De Houwer, Jan; Van Meerbeeck, Jan; Nackaerts, Kristiaan

2015-07-01

It has previously been argued that implicit attitudes toward substance-related cues drive addictive behavior. Nevertheless, it remains an open question whether behavioral markers of implicit attitude activation can be used to predict long-term relapse. The main objective of this study was to examine the relationship between implicit attitudes toward smoking-related cues and long-term relapse in abstaining smokers. Implicit attitudes toward smoking-related cues were assessed by means of the Implicit Association Test (IAT) and the evaluative priming task (EPT). Both measures were completed by a group of smokers who volunteered to quit smoking (patient group) and a group of nonsmokers (control group). Participants in the patient group completed these measures twice: once prior to smoking cessation and once after smoking cessation. Relapse was assessed by means of short telephone survey, 6 months after completion of the second test session. EPT scores obtained prior to smoking cessation were related to long-term relapse and correlated with self-reported nicotine dependence as well as daily cigarette consumption. In contrast, none of the behavioral outcome measures were found to correlate with the IAT scores. These findings corroborate the idea that implicit attitudes toward substance-related cues are critically involved in long-term relapse. A potential explanation for the divergent findings obtained with the IAT and EPT is provided.

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

PubMed

Håkansson, I; Tisell, A; Cassel, P; Blennow, K; Zetterberg, H; Lundberg, P; Dahle, C; Vrethem, M; Ernerudh, J

2017-05-01

Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity. © 2017 EAN.

Gender Differences in Intended Escalatory Tendencies among Marital Partners

ERIC Educational Resources Information Center

Winstok, Zeev; Straus, Murray A.

2011-01-01

This study addresses the intended escalatory tendency in eight hypothetical situations in which the provocator's identity (partner or stranger, male or female) and the provocation form (verbal or physical aggression) were manipulated. The research question is "how does the identity of the provocator and the form of his or her provocation…

The Power of the Provocative: Exploring World History Content

ERIC Educational Resources Information Center

Ashkettle, Bryan L.

2013-01-01

This study addresses how my freshman world history students come to understand controversial issues as provocative within the secondary social studies classroom, and in what ways does their engagement with provocative issues influence their understanding of the content and the world around them. In addition, this research study seeks to discover…

Verbal ability and delinquency: testing the moderating role of psychopathic traits.

PubMed

Muñoz, Luna C; Frick, Paul J; Kimonis, Eva R; Aucoin, Katherine J

2008-04-01

Impaired verbal abilities are one of the most consistent risk factors for serious antisocial and delinquent behavior. However, individuals with psychopathic traits often show serious antisocial behavior, despite showing no impairment in their verbal abilities. Thus, the aim of the current study was to examine whether psychopathy moderates the relationship between verbal abilities and delinquent behavior in a sample of detained youth. The sample included 100 detained adolescent boys who were assessed on self-reported delinquent acts and psychopathic traits, as well as their age at first offense based on official records. Participants also completed a competitive computer task involving two levels of provocation, during which skin conductance was measured. A standard measure of receptive vocabulary was individually administered. As predicted, there was a significant interaction between callous-unemotional (CU) traits (a critical dimension of psychopathy) and verbal ability when predicting violent delinquency. Individuals who were high on CU traits with higher scores on the measure of verbal abilities reported the greatest violent delinquency. These individuals also showed the lowest level of skin conductance reactivity during the provocation task. The results suggest CU traits are an important moderator of the relation between verbal abilities and violent delinquency.

Nonimmediate hypersensitivity reactions to iodinated contrast media.

PubMed

Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

2013-08-01

To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

PubMed

Pepper, Ruth J; Draibe, Juliana B; Caplin, Ben; Fervenza, Fernando C; Hoffman, Gary S; Kallenberg, Cees G M; Langford, Carol A; Monach, Paul A; Seo, Philip; Spiera, Robert; William St Clair, E; Tchao, Nadia K; Stone, John H; Specks, Ulrich; Merkel, Peter A; Salama, Alan D

2017-01-01

S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment. © 2016, American College of Rheumatology.

Efficacy of assessing circulating cell-free DNA using a simple fluorescence assay in patients with triple-negative breast cancer receiving neoadjuvant chemotherapy: a prospective observational study

PubMed Central

Park, Kwonoh; Woo, Miyoung; Kim, Jeong Eun; Ahn, Jin-Hee; Jung, Kyung Hae; Roh, Jin; Gong, Gyungyub; Kim, Sung-Bae

2018-01-01

This study aims to assess cell-free DNA (CFD) by a fluorescence assay as a biomarker for early prediction of a pathologic complete response (pCR) and relapse in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy. Patients with clinical stage II or III TNBC scheduled for neoadjuvant chemotherapy were prospectively enrolled. All patients underwent four cycles of Adriamycin plus cyclophosphamide (AC), followed by four cycles of cisplatin or docetaxel chemotherapy and surgery. Blood samples were obtained before the initial chemotherapy (baseline-CFD) and after four AC neoadjuvant chemotherapy cycles (AC-CFD) to evaluate CFD levels. In total, 72 patients who met the inclusion criteria were enrolled. The mean baseline-CFD and AC-CFD levels were 239 ± 68 and 210 ± 66 ng/mL, respectively, with a significant decline in the CFD levels after AC neoadjuvant chemotherapy (P = 0.001). In the 33.6-month median follow-up, 18 cases of relapse were reported. A ROC curve analysis of baseline-CFD was performed to determine the predictive value for relapse, and an area under the curve of 0.62 (95% CI, 0.46–0.78) at 264 ng/mL was obtained. Patients with baseline-CFD >264 ng/mL were at a higher risk of relapse than those with baseline-CFD ≤264 ng/mL (HR, 2.84; 95% CI, 1.11–7.24; P = 0.029). Multivariate analysis established baseline-CFD as an independent predicting factor for relapse (HR, 3.74; 95% CI, 1.32–10.53; P = 0.013). In conclusion, baseline-CFD measured by a fluorescence assay might be a potential biomarker to predict relapse, which could be useful for risk stratification of TNBC. PMID:29423090

Deep NPM1 Sequencing Following Allogeneic Hematopoietic Cell Transplantation Improves Risk Assessment in Adults with NPM1-Mutated AML.

PubMed

Zhou, Yi; Othus, Megan; Walter, Roland B; Estey, Elihu H; Wu, David; Wood, Brent L

2018-04-21

Relapse is the major cause of death in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT). Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) before and after HCT is a strong, independent risk factor for relapse. As next-generation sequencing (NGS) is increasingly applied in AML MRD detection, it remains to be determined if NGS can improve prediction of post-HCT relapse. Herein, we investigated pre-HCT MRD detected by MFC and NGS in 59 adult patients with NPM1-mutated AML in morphologic remission; 45 of the 59 had post-HCT MRD determined by MFC and NGS around day 28. Before HCT, MRD detected by MFC was the most significant risk factor for relapse (hazard ratio [HR], 4.63; P < .001), whereas MRD detected only by NGS was not. After HCT, MRD detected by either MFC or NGS was significant risk factor for relapse (HR, 4.96, P = .004 and HR, 4.36, P = .002, respectively). Combining pre- and post-HCT MRD provided the best prediction for relapse (HR, 5.25; P < .001), with a sensitivity at 83%. We conclude that NGS testing of mutated NPM1 post-HCT improves the risk assessment for relapse, whereas pre-HCT MFC testing identifies a subset of high-risk patients in whom additional therapy should be tested. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

North Korea’s Choice of the Types of Provocation Against South Korea

DTIC Science & Technology

2013-12-01

DISTRIBUTION CODE A 13. ABSTRACT (maximum 200 words) This research starts from the question of how North Korea decides upon the types of its provocations...INTENTIONALLY LEFT BLANK iv ABSTRACT This research starts from the question of how North Korea decides upon the types of its provocations...1 A. MAJOR RESEARCH QUESTION................................................................1 B

High Index Values of Enzyme-Linked Immunosorbent Assay for BP180 at Baseline Predict Relapse in Patients With Bullous Pemphigoid

PubMed Central

Koga, Hiroshi; Teye, Kwesi; Ishii, Norito; Ohata, Chika; Nakama, Takekuni

2018-01-01

Bullous pemphigoid (BP) presenting with erythema plaques and tense blisters is the most frequent autoimmune bullous disease. Immunologically, BP is characterized by the presence of circulating anti-epidermal basement membrane zone (BMZ) antibodies. The autoantigens in BMZs targeted by patient's antibodies are mainly BP180 (type XVII collagen) and BP230. Previous reports have indicated that IgG to the immunodominant region of BP180 in BP, 16th non-collagenous domain (NC16A), and anti-BP180NC16A IgE are related to disease activity. In the cytokine profile, serum levels of IL-6, TNF-α, IL-15, and CCL18 were associated with the severity or activity of the disease. Blood eosinophilia is seen frequently, especially in severe cases. These biomarkers are helpful to evaluate efficacy of treatment and disease severity. Due to the high frequency of disease relapse, prediction of relapse at initiation of treatment (baseline) must be beneficial for clinicians. Therefore, we evaluated biomarkers anti-BP180 IgG (BP180 ELISA), anti-BP230 IgG (BP230 ELISA), peripheral eosinophils, and serum IgE at baseline between BP patients with (n = 16) and without (n = 31) relapse. We found significantly higher index values of BP180 ELISA in the relapse group, whereas no significant difference was found in BP230 ELISA, peripheral eosinophils, and serum IgE. This study indicated that a high index value of BP180 ELISA (cutoff value, 53.09 U/mL; sensitivity, 81.3%; specificity, 48.4%) at baseline may predict relapse in patients with BP. This may help clinicians treating BP patients in decision-making regarding duration and intensity of treatment. PMID:29868591

Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence in a European-wide population-based cohort.

PubMed

Höie, Ole; Wolters, Frank; Riis, Lene; Aamodt, Geir; Solberg, Camilla; Bernklev, Tomm; Odes, Selwyn; Mouzas, Iannis A; Beltrami, Marina; Langholz, Ebbe; Stockbrügger, Reinhold; Vatn, Morten; Moum, Bjorn

2007-08-01

Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to almost 100% have been reported in regional studies. The aim of this study was to determine the relapse rate in UC in a European population-based cohort 10 yr after diagnosis and to identify factors that may influence the risk of relapse. From 1991 to 1993, 771 patients with UC from seven European countries and Israel were prospectively included in a population-based inception cohort and followed for 10 yr. A relapse was defined as an increase in UC-related symptoms leading to changes in medical treatment or surgery. The cumulative relapse rate, time to first relapse, and number of relapses in the follow-up period were recorded and possible causative factors were investigated. The cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI 0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI 1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1-1.8). The number of relapses decreased with age, and current smokers had a lower relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2 (CI 1.1-1.3) times higher than in men. An inverse relation was found between the time to the first relapse and the total number of relapses. In 67% of patients, there was at least one relapse. Smoking status, level of education, and possibly female gender were found to influence the risk of relapse.

Microbiome interaction with sugar plays an important role in relapse of childhood caries.

PubMed

Tian, Jing; Qin, Man; Ma, Wenli; Xia, Bin; Xu, He; Zhang, Qian; Chen, Feng

Childhood caries have a high relapse rate after full mouth therapy. This study aimed to elucidate the relationship between the microbiome, sugar, and the relapse of childhood caries after therapy. A total of 24 children aged 2-4 years who underwent one caries treatment session participated in this study. Supragingival plaque was collected before therapy and 1 and 7 months after therapy, then sequenced using the 16S rRNA high-throughput approach. We found 11 phyla, 140 genera, and 444 species in 72 samples. The children were divided into relapse-free (n = 13) and relapse (n = 11) groups according to whether they relapsed 7 months after therapy. The bacterial community richness, diversity, structure, and relative abundance of bacterial taxa were significantly different between the two groups 7 months after therapy. The two groups also differed in the relative abundance of bacterial taxa, both before and 1 month after therapy. Bacterial community richness and diversity were lower in the relapse-free group 1 month after therapy. Using different operational taxonomic units between the relapse-free and relapse groups 1 month after therapy, a relapse-risk assessment model was built with 75% accuracy, 0.1905 out-of-bag error, and 66.67% validation accuracy. Patients in the relapse group had higher sugar intake frequencies than those in the relapse-free group during follow-up. Interactions between the microbiome and sugar intake frequency were found through co-occurrence networks. We conclude that the microbiome is significantly different between the relapse-free and relapse groups at the time of relapse. Supragingival plaque collected immediately after therapy can be used to predict the risk of relapse. Furthermore, the correlation between sugar intake frequency and microbiome is associated with the relapse. Copyright © 2015 Elsevier Inc. All rights reserved.

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study.

PubMed

Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-08-18

Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Forty MMT patients were included and received a 12-month follow-up. All patients were given baseline resting-state fMRI scans by using a 3.0 T GE Signa Excite HD whole-body MRI system. Monthly self-report and urine test were used to assess heroin relapse or non-relapse. Subjective craving was measured with visual analog scale. The correlation between ReHo and the degree of heroin relapse was analyzed. Compared with the non-relapsers, ReHo values were increased in the bilateral medial orbitofrontal cortex, right caudate, and right cerebellum of the heroin relapsers while those in the left parahippocampal gyrus, left middle temporal gyrus, right lingual gyrus, and precuneus were decreased in heroin relapsers. Importantly, altered ReHo in the right caudate were positively correlated with heroin relapse rates or subjective craving response. Using the resting-state fMRI technique by analysis of ReHo, we provided the first resting-state fMRI evidence that right caudate may serve as a potential biomarker for heroin relapse prediction and also as a promising target for reducing relapse risk.

Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia.

PubMed

Aplenc, Richard; Thompson, Jennifer; Han, Peggy; La, Mei; Zhao, Huaqing; Lange, Beverly; Rebbeck, Timothy

2005-03-15

A significant portion of patients treated for pediatric acute lymphoblastic leukemia (ALL) relapse. We hypothesized that common polymorphisms with moderate effect sizes and large attributive risks could explain an important fraction of ALL relapses. Methylenetetrahydrofolate reductase (MTHFR) is central to folate metabolism and has two common functional polymorphisms (C677T and A1298G). Methotrexate (MTX), which interrupts folate metabolism, is a mainstay of pediatric ALL therapy. MTX inhibits the synthesis of dTMP needed for DNA replication by blocking the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate by MTHFR. We hypothesized that a deactivating MTHFR allele would increase ALL relapse risk by potentially increasing 5,10-methylenetetrahydrofolate and dTMP, enhancing DNA synthesis and thus opposing MTX. To test this hypothesis, we genotyped 520 patients on the Children's Cancer Study Group ALL study, CCG-1891. The MTHFR C677T variant allele was statistically significantly associated with relapse (chi2 = 4.38, P = 0.036). This association remained significant (hazard ratio = 1.82, P = 0.008), controlling for important covariates, and was more predictive of relapse than other predictors, including day 7 bone marrow response. The MTHFR C677T variant allele was not associated with an increased risk of toxicity or infection. The MTHFR A1298G polymorphism was not associated with altered risks of relapse, toxicity, or infection. Haplotype analysis showed six common haplotypes that did not provide additional information predictive for relapse. These data provide evidence that the MTHFR C677T polymorphism is a common genetic variant conferring a moderate relative risk and a high attributable risk for relapse in pediatric ALL patients.

Common genetic variation within miR-146a predicts disease onset and relapse in multiple sclerosis.

PubMed

Zhou, Yuan; Chen, Ming; Simpson, Steve; Lucas, Robyn M; Charlesworth, Jac C; Blackburn, Nicholas; van der Mei, Ingrid; Ponsonby, Anne-Louise; Taylor, Bruce V

2018-02-01

Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.

School-Level Genetic Variation Predicts School-Level Verbal IQ Scores: Results from a Sample of American Middle and High Schools

ERIC Educational Resources Information Center

Beaver, Kevin M.; Wright, John Paul

2011-01-01

Research has consistently revealed that average IQ scores vary significantly across macro-level units, such as states and nations. The reason for this variation in IQ, however, has remained at the center of much controversy. One of the more provocative explanations is that IQ across macro-level units is the result of genetic differences, but…

Unbalanced Nature, Unbounded Bodies, and Unlimited Technology: Ecocriticism and Karen Traviss' Wess'har Series

ERIC Educational Resources Information Center

Sullivan, Heather I.

2010-01-01

While nature is often claimed to be a space of harmonized balance or an antidote to the chaos of the modern world, we need a more grounded assessment of nature as endlessly changing and much less predictable than we like to assume. In this essay, I explore Karen Traviss' provocative exploration of unbalanced nature and unbounded bodies in her…

Reduced fMRI activity predicts relapse in patients recovering from stimulant dependence.

PubMed

Clark, Vincent P; Beatty, Gregory K; Anderson, Robert E; Kodituwakku, Piyadassa; Phillips, John P; Lane, Terran D R; Kiehl, Kent A; Calhoun, Vince D

2014-02-01

Relapse presents a significant problem for patients recovering from stimulant dependence. Here we examined the hypothesis that patterns of brain function obtained at an early stage of abstinence differentiates patients who later relapse versus those who remain abstinent. Forty-five recently abstinent stimulant-dependent patients were tested using a randomized event-related functional MRI (ER-fMRI) design that was developed in order to replicate a previous ERP study of relapse using a selective attention task, and were then monitored until 6 months of verified abstinence or stimulant use occurred. SPM revealed smaller absolute blood oxygen level-dependent (BOLD) response amplitude in bilateral ventral posterior cingulate and right insular cortex in 23 patients positive for relapse to stimulant use compared with 22 who remained abstinent. ER-fMRI, psychiatric, neuropsychological, demographic, personal and family history of drug use were compared in order to form predictive models. ER-fMRI was found to predict abstinence with higher accuracy than any other single measure obtained in this study. Logistic regression using fMRI amplitude in right posterior cingulate and insular cortex predicted abstinence with 77.8% accuracy, which increased to 89.9% accuracy when history of mania was included. Using 10-fold cross-validation, Bayesian logistic regression and multilayer perceptron algorithms provided the highest accuracy of 84.4%. These results, combined with previous studies, suggest that the functional organization of paralimbic brain regions including ventral anterior and posterior cingulate and right insula are related to patients' ability to maintain abstinence. Novel therapies designed to target these paralimbic regions identified using ER-fMRI may improve treatment outcome. Copyright © 2012 Wiley Periodicals, Inc.

Predicting Relapse in Patients With Medulloblastoma by Integrating Evidence From Clinical and Genomic Features

PubMed Central

Tamayo, Pablo; Cho, Yoon-Jae; Tsherniak, Aviad; Greulich, Heidi; Ambrogio, Lauren; Schouten-van Meeteren, Netteke; Zhou, Tianni; Buxton, Allen; Kool, Marcel; Meyerson, Matthew; Pomeroy, Scott L.; Mesirov, Jill P.

2011-01-01

Purpose Despite significant progress in the molecular understanding of medulloblastoma, stratification of risk in patients remains a challenge. Focus has shifted from clinical parameters to molecular markers, such as expression of specific genes and selected genomic abnormalities, to improve accuracy of treatment outcome prediction. Here, we show how integration of high-level clinical and genomic features or risk factors, including disease subtype, can yield more comprehensive, accurate, and biologically interpretable prediction models for relapse versus no-relapse classification. We also introduce a novel Bayesian nomogram indicating the amount of evidence that each feature contributes on a patient-by-patient basis. Patients and Methods A Bayesian cumulative log-odds model of outcome was developed from a training cohort of 96 children treated for medulloblastoma, starting with the evidence provided by clinical features of metastasis and histology (model A) and incrementally adding the evidence from gene-expression–derived features representing disease subtype–independent (model B) and disease subtype–dependent (model C) pathways, and finally high-level copy-number genomic abnormalities (model D). The models were validated on an independent test cohort (n = 78). Results On an independent multi-institutional test data set, models A to D attain an area under receiver operating characteristic (au-ROC) curve of 0.73 (95% CI, 0.60 to 0.84), 0.75 (95% CI, 0.64 to 0.86), 0.80 (95% CI, 0.70 to 0.90), and 0.78 (95% CI, 0.68 to 0.88), respectively, for predicting relapse versus no relapse. Conclusion The proposed models C and D outperform the current clinical classification schema (au-ROC, 0.68), our previously published eight-gene outcome signature (au-ROC, 0.71), and several new schemas recently proposed in the literature for medulloblastoma risk stratification. PMID:21357789

Smoker Characteristics and Smoking-Cessation Milestones

PubMed Central

Japuntich, Sandra J.; Leventhal, Adam M.; Piper, Megan E.; Bolt, Daniel M.; Roberts, Linda J.; Fiore, Michael C.; Baker, Timothy B.

2011-01-01

Background Contextual variables often predict long-term abstinence, but little is known about how these variables exert their effects. These variables could influence abstinence by affecting the ability to quit at all, or by altering risk of lapsing, or progressing from a lapse to relapse. Purpose To examine the effect of common predictors of smoking-cessation failure on smoking-cessation processes. Methods The current study (N = 1504, 58% female, 84% Caucasian; recruited from January 2005 to June 2007; data analyzed in 2009) uses the approach advocated by Shiffman et al., (2006), which measures cessation outcomes on three different cessation milestones (achieving initial abstinence, lapse risk, and the lapse-relapse transition) to examine relationships of smoker characteristics (dependence, contextual and demographic factors) with smoking-cessation process. Results High nicotine dependence strongly predicted all milestones: not achieving initial abstinence, and a higher risk of both lapse and transitioning from lapse to complete relapse. Numerous contextual and demographic variables were associated with higher initial cessation rates and/or decreased lapse risk at 6 months post-quit (e.g., ethnicity, gender, marital status, education, smoking in the workplace, number of smokers in the social network, and number of supportive others). However, aside from nicotine dependence, only gender significantly predicted the risk of transition from lapse to relapse. Conclusions These findings demonstrate that: (1) higher nicotine dependence predicted worse outcomes across every cessation milestone; (2) demographic and contextual variables are generally associated with initial abstinence rates and lapse risk and not the lapse-relapse transition. These results identify groups who are at risk for failure at specific stages of the smoking-cessation process, and this may have implications for treatment. PMID:21335259

Surveillance imaging in mantle cell lymphoma in first remission lacks clinical utility.

PubMed

Guidot, Daniel M; Switchenko, Jeffrey M; Nastoupil, Loretta J; Koff, Jean L; Blum, Kristie A; Maly, Joseph; Flowers, Christopher R; Cohen, Jonathon B

2018-04-01

Mantle cell lymphoma (MCL) is a heterogeneous disease with high relapse rates. Limited data guide the use of surveillance imaging following treatment. We constructed a retrospective cohort from two academic institutions of patients with MCL who completed first-line therapy and underwent follow-up for relapse, analyzing the effect of surveillance imaging on survival. Of 217 patients, 102 had documented relapse, with 38 (37%) diagnosed by surveillance imaging and 64 (63%) by other methods. Relapse diagnosis by surveillance imaging had no significant advantage in overall survival from diagnosis date (hazard ratio [HR] = 0.80, p = .39) or relapse date (HR = 0.72, p = .22). Of 801 surveillance images, PET/CT had a positive predictive value (PPV) of 24% and number needed-to-scan/treat (NNT) of 51 to detect one relapse, and CT had a PPV of 49% and NNT of 24. For MCL after first-line therapy, relapse detection by surveillance imaging was not associated with improved survival and lacks clinical benefit.

Changes in circulating peptide YY and ghrelin are associated with early smoking relapse.

PubMed

Lemieux, Andrine M; al'Absi, Mustafa

2018-01-01

Ghrelin and peptide YY (PYY) during ad libitum smoking have been associated with decreased reported craving (ghrelin) and increased positive affect (PYY), and higher baseline ghrelin levels predicted subsequent increased risk of smoking relapse. The current study assessed PYY and ghrelin during ad libitum smoking and again after the initial 48h of a smoking cessation attempt. The data compared smokers who abstained for 28days (n=37), smokers who relapsed (n=54), and nonsmokers (n=37). Plasma samples and subjective measures assessing craving and mood were collected at the beginning of each session. Results showed that relapsers experienced greater levels of distress (ps <0.01). While nonsmokers and abstainers showed no change in ghrelin across the initial 48h, relapsers declined (p <0.01). With PYY, relapsers increased (p <0.05) across the early abstinent phase. PYY and ghrelin may be useful predictors of relapse, specifically in reference to early withdrawal. Copyright © 2017. Published by Elsevier B.V.

In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome

PubMed Central

Romero, Lucia; Trenor, Beatriz; Yang, Pei-Chi; Saiz, Javier; Clancy, Colleen E.

2014-01-01

Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired Long-QT Syndrome (aLTQS). We developed a computational approach to reveal the pharmacological properties of IKr blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in IKr channel gating that would be expected to result from benign genetic variants. We used the model to predict the most potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed “in silico mutagenesis” by altering discrete kinetic transition rates of the Fink et al. Markov model of human IKr channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of IKr channels. We then screened and identified the properties of IKr blockers that caused acquired Long QT and therefore unmasked mutant phenotypes for mild, moderate and severe variants. Mutant IKr channels were incorporated into the O’Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of IKr-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and IKr mutated cells. Our results show that drugs with disparate affinities to conformation states of the IKr channel are key to amplify variants underlying susceptibility to acquired Long QT Syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical formulation of the M54T MiRP1 latent mutation and simulated a provocative test. In this setting, application of dofetilide dramatically amplified the predicted QT interval duration in the M54T hMiRP1 mutation compared to wild-type. PMID:24631769

Social Resource Characteristics and Adolescent Substance Abuse Relapse.

ERIC Educational Resources Information Center

Vik, Peter W.; And Others

1992-01-01

Examined social resource network characteristics of adolescent substance abusers (n=19). Perceived similarity to one's social network emerged as important moderator of whether social network provided support to remain abstinent or elevated risk for relapse. Increased perceived support predicted continued posttreatment abstinence when recovering…

Relapse following antithyroid drug therapy for Graves' hyperthyroidism.

PubMed

Laurberg, Peter; Krejbjerg, Anne; Andersen, Stine Linding

2014-10-01

In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Evaluation of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation.

PubMed

Lee, Nam-Ki; Kim, Young-Kyun; Yun, Pil-Young; Kim, Jong-Wan

2013-01-01

The aim of this study was to evaluate of the patterns of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation (MS-MO). The subjects consisted of 15 patients with minimal pre-surgical orthodontic preparation (1.37 ± 1.69 months). Lateral cephalograms were taken in pre-surgical (T0), post-surgical 1 month (T1) and immediately after debonding (T2) stages. To evaluate the surgical changes (T1-T0) and the relapse (T2-T1), the linear and angular measurements were analyzed using paired t-test. Pearson's correlation coefficients of the horizontal and vertical relapses of Pog and Me to other measurements were calculated. Pog or Me in T1 were displaced rotationally on Ar-Pog or Ar-Me lines in T2 to evaluate the remaining surgical relapse except the rotational relapse from total relapse. The mandible relapsed anteriorly 3.53 mm (Pog) and 4.00 mm (Me) and superiorly 2.72 mm (Pog) and 2.44 mm (Me). FH to Ar-Pog and FH to Ar-Me decreased by about 2°. Pure surgical relapses at Pog and Me, except rotational relapses, were about 0.5 mm anteriorly and inferiorly 0.8 mm. The vertical relapse might induce mandibular rotation with the horizontal relapse. For an accurate prediction after MS-MO, the rotational relapse might be considered. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Renal Tumor Anatomic Complexity: Clinical Implications for Urologists.

PubMed

Joshi, Shreyas S; Uzzo, Robert G

2017-05-01

Anatomic tumor complexity can be objectively measured and reported using nephrometry. Various scoring systems have been developed in an attempt to correlate tumor complexity with intraoperative and postoperative outcomes. Nephrometry may also predict tumor biology in a noninvasive, reproducible manner. Other scoring systems can help predict surgical complexity and the likelihood of complications, independent of tumor characteristics. The accumulated data in this new field provide provocative evidence that objectifying anatomic complexity can consolidate reporting mechanisms and improve metrics of comparisons. Further prospective validation is needed to understand the full descriptive and predictive ability of the various nephrometry scores. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of family expressed emotion and perceived social support in predicting addiction relapse.

PubMed

Atadokht, Akbar; Hajloo, Nader; Karimi, Masoud; Narimani, Mohammad

2015-03-01

Emotional conditions governing the family and patients' perceived social support play important roles in the treatment or relapse process of the chronic disease. The current study aimed to investigate the role of family expressed emotion and perceived social support in prediction of addiction relapse. The descriptive-correlation method was used in the current study. The study population consisted of the individuals referred to the addiction treatment centers in Ardabil from October 2013 to January 2014. The subjects (n = 80) were randomly selected using cluster sampling method. To collect data, expressed emotion test by Cole and Kazaryan, and Multidimensional Scale of Perceived Social Support (MSPSS) were used, and the obtained data was analyzed using the Pearson's correlation coefficient and multiple regression analyses. Results showed a positive relationship between family expressed emotions and the frequency of relapse (r = 0.26, P = 0.011) and a significant negative relationship between perceived social support and the frequency of relapse (r = -0.34, P = 0.001). Multiple regression analysis also showed that perceived social support from family and the family expressed emotions significantly explained 12% of the total variance of relapse frequency. These results have implications for addicted people, their families and professionals working in addiction centers to use the emotional potential of families especially their expressed emotions and the perceived social support of addicts to increase the success rate of addiction treatment.

Integrity of Literature on Expressed Emotion and Relapse in Patients with Schizophrenia Verified by a p-Curve Analysis.

PubMed

Weintraub, Marc J; Hall, Daniel L; Carbonella, Julia Y; Weisman de Mamani, Amy; Hooley, Jill M

2017-06-01

There is growing concern that much published research may have questionable validity due to phenomena such as publication bias and p-hacking. Within the psychiatric literature, the construct of expressed emotion (EE) is widely assumed to be a reliable predictor of relapse across a range of mental illnesses. EE is an index of the family climate, measuring how critical, hostile, and overinvolved a family member is toward a mentally ill patient. No study to date has examined the evidential value of this body of research as a whole. That is to say, although many studies have shown a link between EE and symptom relapse, the integrity of the literature from which this claim is derived has not been tested. In an effort to confirm the integrity of the literature of EE predicting psychiatric relapse in patients with schizophrenia, we conducted a p-curve analysis on all known studies examining EE (using the Camberwell Family Interview) to predict psychiatric relapse over a 9- to 12-month follow-up period. Results suggest that the body of literature on EE is unbiased and has integrity, as there was a significant right skew of p-values, a nonsignificant left skew of p-values, and a nonsignificant test of flatness. We conclude that EE is a robust and valuable predictor of symptom relapse in schizophrenia. © 2016 Family Process Institute.

Integrity of Literature on Expressed Emotion and Relapse in Patients with Schizophrenia Verified by a p-Curve Analysis

PubMed Central

WEINTRAUB, MARC J.; HALL, DANIEL L.; CARBONELLA, JULIA Y.; DE MAMANI, AMY WEISMAN; HOOLEY, JILL M.

2018-01-01

There is growing concern that much published research may have questionable validity due to phenomena such as publication bias and p-hacking. Within the psychiatric literature, the construct of expressed emotion (EE) is widely assumed to be a reliable predictor of relapse across a range of mental illnesses. EE is an index of the family climate, measuring how critical, hostile, and overinvolved a family member is toward a mentally ill patient. No study to date has examined the evidential value of this body of research as a whole. That is to say, although many studies have shown a link between EE and symptom relapse, the integrity of the literature from which this claim is derived has not been tested. In an effort to confirm the integrity of the literature of EE predicting psychiatric relapse in patients with schizophrenia, we conducted a p-curve analysis on all known studies examining EE (using the Camberwell Family Interview) to predict psychiatric relapse over a 9- to 12-month follow-up period. Results suggest that the body of literature on EE is unbiased and has integrity, as there was a significant right skew of p-values, a nonsignificant left skew of p-values, and a nonsignificant test of flatness. We conclude that EE is a robust and valuable predictor of symptom relapse in schizophrenia. PMID:26875506

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

PubMed

Göçeroğlu, Arda; Berden, Annelies E; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D; Hagen, E Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A; Jayne, David R W; Bajema, Ingeborg M

2016-01-01

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

PubMed Central

Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.

2016-01-01

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575

Using decision tree analysis to identify risk factors for relapse to smoking

PubMed Central

Piper, Megan E.; Loh, Wei-Yin; Smith, Stevens S.; Japuntich, Sandra J.; Baker, Timothy B.

2010-01-01

This research used classification tree analysis and logistic regression models to identify risk factors related to short- and long-term abstinence. Baseline and cessation outcome data from two smoking cessation trials, conducted from 2001 to 2002, in two Midwestern urban areas, were analyzed. There were 928 participants (53.1% women, 81.8% white) with complete data. Both analyses suggest that relapse risk is produced by interactions of risk factors and that early and late cessation outcomes reflect different vulnerability factors. The results illustrate the dynamic nature of relapse risk and suggest the importance of efficient modeling of interactions in relapse prediction. PMID:20397871

A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients.

PubMed

Won, Young-Woong; Joo, Jungnam; Yun, Tak; Lee, Geon-Kook; Han, Ji-Youn; Kim, Heung Tae; Lee, Jin Soo; Kim, Moon Soo; Lee, Jong Mog; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Sohee

2015-05-01

Development of brain metastasis results in a significant reduction in overall survival. However, there is no an effective tool to predict brain metastasis in non-small cell lung cancer (NSCLC) patients. We conducted this study to develop a feasible nomogram that can predict metastasis to the brain as the first relapse site in patients with curatively resected NSCLC. A retrospective review of NSCLC patients who had received curative surgery at National Cancer Center (Goyang, South Korea) between 2001 and 2008 was performed. We chose metastasis to the brain as the first relapse site after curative surgery as the primary endpoint of the study. A nomogram was modeled using logistic regression. Among 1218 patients, brain metastasis as the first relapse developed in 87 patients (7.14%) during the median follow-up of 43.6 months. Occurrence rates of brain metastasis were higher in patients with adenocarcinoma or those with a high pT and pN stage. Younger age appeared to be associated with brain metastasis, but this result was not statistically significant. The final prediction model included histology, smoking status, pT stage, and the interaction between adenocarcinoma and pN stage. The model showed fairly good discriminatory ability with a C-statistic of 69.3% and 69.8% for predicting brain metastasis within 2 years and 5 years, respectively. Internal validation using 2000 bootstrap samples resulted in C-statistics of 67.0% and 67.4% which still indicated good discriminatory performances. The nomogram presented here provides the individual risk estimate of developing metastasis to the brain as the first relapse site in patients with NSCLC who have undergone curative surgery. Surveillance programs or preventive treatment strategies for brain metastasis could be established based on this nomogram. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: some preliminary evidence from event-related potentials

PubMed Central

Petit, Géraldine; Cimochowska, Agnieszka; Kornreich, Charles; Hanak, Catherine; Verbanck, Paul; Campanella, Salvatore

2014-01-01

Background Alcohol dependence is a chronic relapsing disease. The impairment of response inhibition and alcohol-cue reactivity are the main cognitive mechanisms that trigger relapse. Despite the interaction suggested between the two processes, they have long been investigated as two different lines of research. The present study aimed to investigate the interaction between response inhibition and alcohol-cue reactivity and their potential link with relapse. Materials and methods Event-related potentials were recorded during a variant of a “go/no-go” task. Frequent and rare stimuli (to be inhibited) were superimposed on neutral, nonalcohol-related, and alcohol-related contexts. The task was administered following a 3-week detoxification course. Relapse outcome was measured after 3 months, using self-reported abstinence. There were 27 controls (seven females) and 27 patients (seven females), among whom 13 relapsed during the 3-month follow-up period. The no-go N2, no-go P3, and the “difference” wave (P3d) were examined with the aim of linking neural correlates of response inhibition on alcohol-related contexts to the observed relapse rate. Results Results showed that 1) at the behavioral level, alcohol-dependent patients made significantly more commission errors than controls (P<0.001), independently of context; 2) through the subtraction no-go P3 minus go P3, this inhibition deficit was neurophysiologically indexed in patients with greater P3d amplitudes (P=0.034); and 3) within the patient group, increased P3d amplitude enabled us to differentiate between future relapsers and nonrelapsers (P=0.026). Conclusion Our findings suggest that recently detoxified alcoholics are characterized by poorer response-inhibition skills that demand greater neural resources. We propose that event-related potentials can be used in conjunction with behavioral data to predict relapse; this would identify patients that need a higher level of neural resources when suppressing a response is requested. PMID:24966675

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

PubMed

Rustad, James K; Stern, Theodore A; Prabhakar, Maithri; Musselman, Dominique

2015-01-01

Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Immunologic prediction of relapse in patients with pemphigus vulgaris (PV) in clinical remission.

PubMed

Daneshpazhooh, Maryam; Zafarmand Sedigh, Vahid; Balighi, Kamran; Hosseini, S Hamed; Ramezani, Ali; Kalantari, Mohammad-Sadegh; Ghandi, Narges; Ghiasi, Maryam; Nikoo, Azita; Chams-Davatchi, Cheyda

2016-06-01

Pemphigus vulgaris (PV) is characterized by multiple relapses, occurring especially in patients on minimal therapy or off therapy. To identify immunologic predictors (anti-desmoglein [Dsg] 1 and 3 antibodies; direct immunofluorescence [DIF]) for relapse in PV patients. Eighty-nine patients in complete clinical remission for at least 6 months and receiving less than or equal to 10 mg prednisolone daily and no immunosuppressive drugs were evaluated using DIF (n=89) and Dsg ELISA (n=46). They were followed until relapse or for at least 18 months. DIF was positive in 44 of 89 patients (49.5%); anti-Dsg 3 antibodies were detected in 18 of 46 patients (39.1%) and anti-Dsg 1 antibodies were detected in 4 of 46 patients (8.7%). Relapse occurred in 38 patients (42.7%). Mean relapse-free time was significantly shorter in anti-Dsg 3-positive patients compared to anti-Dsg 3- negative patients (P = .015) and in DIF-positive patients compared to DIF-negative patients (P = .047), but not in anti-Dsg 1- positive patients compared to anti-Dsg 1-negative patients (P = .501). Sensitivity and predictive values of neither of these tests were high. Small number of anti-Dsg 1-positive patients and use of conventional ELISA. Positive anti-Dsg 3 ELISA and, to a lesser degree, positive DIF are predictors of relapse in PV patients in clinical remission. Decision on discontinuing treatment should be based on the results of these tests as well as on clinical findings. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Natural History of Benign Nonimmediate Allergy to Beta-Lactams in Children: A Prospective Study in Retreated Patients After a Positive and a Negative Provocation Test.

PubMed

Tonson la Tour, Aude; Michelet, Marine; Eigenmann, Philippe A; Caubet, Jean-Christoph

2017-11-23

The drug provocation test (DPT) is considered as the gold standard to diagnose drug allergy and is particularly important in the diagnosis of nonimmediate beta-lactam (BL) allergy in children. The natural history of BL allergy remains unknown. Our main aim was to evaluate the natural history of nonimmediate BL hypersensitivity and the long-term tolerance acquisition, and our secondary objective was to determine the negative predictive value (NPV) of the DPT following a 2-day protocol. Children developing a benign rash while treated by BL were prospectively recruited at the Emergency Department of the Geneva University Hospital from 2006 to 2011 and challenged with the incriminated BL (initial diagnostic drug provocation test [idDPT]) following a 2-day protocol. In case of a positive idDPT, the patients underwent a follow-up drug provocation test (fuDPT) 3 years later. In case of a negative idDPT, we sent a questionnaire to assess tolerance of a subsequent treatment with the incriminated BL. Among the 18 children with a positive idDPT, 16 children (89%) had a negative fuDPT and 2 children developed a benign exanthema. Among those 16 children, 11 tolerated a subsequent treatment with the incriminated BL without any reaction, suggesting natural antibiotic tolerance acquisition. From another point of view, we found that the NPV of the DPT following a 2-day protocol was excellent at 96.7%. Our data strongly suggest that a fuDPT is safe and useful to assess tolerance acquisition in children with a confirmed benign nonimmediate BL allergy. In addition, our results support the use of a short DPT protocol (2 days), which led to a high NPV of 96.7% in our population, with a favorable benefit-risk balance. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association between composites of selected motion palpation and pain provocation tests for sacroiliac joint disorders.

PubMed

Soleimanifar, Manijeh; Karimi, Noureddin; Arab, Amir Massoud

2017-04-01

The sacroiliac joint (SIJ) has been implicated as a potential source of low back and buttock pain. Several types of motion palpation and pain provocation tests are used to evaluate SIJ dysfunction. The purpose of this study was to investigate the relationship between motion palpation and pain provocation tests in assessment of SIJ problems. This study is Descriptive Correlation. 50 patients between the ages of 20 and 65 participated. Four motion palpation tests (Sitting flexion, Standing flexion, Prone knee flexion, Gillet test) and three pain provocation tests (FABER, Posterior shear, Resisted abduction test) were examined. Chi-square analysis was used to assess the relationship between results of the individuals and composites of these two groups of tests. No significant relationship was found between these two groups of tests. It seems that motion palpation tests assess SIJ dysfunction and provocative tests assessed SIJ pain which do not appear to be related. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exogenous cortisol facilitates responses to social threat under high provocation.

PubMed

Bertsch, Katja; Böhnke, Robina; Kruk, Menno R; Richter, Steffen; Naumann, Ewald

2011-04-01

Stress is one of the most important promoters of aggression. Human and animal studies have found associations between basal and acute levels of the stress hormone cortisol and (abnormal) aggression. Irrespective of the direction of these changes--i.e., increased or decreased aggressive behavior--the results of these studies suggest dramatic alterations in the processing of threat-related social information. Therefore, the effects of cortisol and provocation on social information processing were addressed by the present study. After a placebo-controlled pharmacological manipulation of acute cortisol levels, we exposed healthy individuals to high or low levels of provocation in a competitive aggression paradigm. Influences of cortisol and provocation on emotional face processing were then investigated with reaction times and event-related potentials (ERPs) in an emotional Stroop task. In line with previous results, enhanced early and later positive, posterior ERP components indicated a provocation-induced enhanced relevance for all kinds of social information. Cortisol, however, reduced an early frontocentral bias for angry faces and--despite the provocation-enhancing relevance--led to faster reactions for all facial expressions in highly provoked participants. The results thus support the moderating role of social information processing in the 'vicious circle of stress and aggression'. Copyright © 2010 Elsevier Inc. All rights reserved.

Quantitative skin prick and bronchial provocation tests with platinum salt.

PubMed Central

Merget, R; Schultze-Werninghaus, G; Bode, F; Bergmann, E M; Zachgo, W; Meier-Sydow, J

1991-01-01

Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts. PMID:1772797

Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement.

PubMed

Córdova-Sánchez, Bertha M; Mejía-Vilet, Juan M; Morales-Buenrostro, Luis E; Loyola-Rodríguez, Georgina; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

2016-07-01

Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.

Alcohol-seeking and relapse: A focus on incentive salience and contextual conditioning.

PubMed

Valyear, Milan D; Villaruel, Franz R; Chaudhri, Nadia

2017-08-01

Environmental stimuli that reliably accompany alcohol intake can become associated with the pharmacological effects of alcohol through classical (Pavlovian) conditioning. Of growing interest to addiction researchers is whether or not this process results in the attribution of incentive salience to alcohol-predictive cues, which could motivate alcohol-seeking behavior and relapse. To evaluate this question, we present a review of rodent behavioral studies that examined the capacity of alcohol-predictive cues to (i) support sign-tracking behavior, (ii) serve as conditioned reinforcers, and (iii) produce Pavlovian-to-instrumental transfer. A second, emerging area of research is focused on delineating the role of context in alcohol-seeking behavior and relapse. Here, we review studies showing that alcohol-associated contexts (i) support conditioned place preference, (ii) renew extinguished alcohol-seeking behavior, and (iii) modulate alcohol-seeking responses elicited by discrete alcohol-predictive cues. These behavioral effects may be mediated by unique psychological processes, and have important implications for cue-reactivity studies and neurobiological research. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of vibration produced by the grinders used in the shipbuilding industry of Korea.

PubMed

Park, Hee-Sok; Yim, Sang-Hyuk

2007-04-01

The objective of this study is to estimate the prevalence of finger blanching among the workers in a shipyard of Korea using the dose-response relationship suggested by ISO 5349. The characteristics of vibration exposure produced by six types of grinders were investigated. Vibration measurement was made under the real work conditions. Exposure time was estimated by questionnaire and direct observation. In addition, cold provocation tests were performed, and the results from the tests were compared with the estimated prevalence. As a result, 4 hour-energy-equivalent frequency-weighted accelerations of the finishing grinding (FG) and the prepainting grinding (PG) jobs were 6.23 m/s(2) and 13.39 m/s(2), respectively. The mean exposure time for holding the grinders was 4.64 h per day. Using the ISO 5349 method, it was predicted that after exposure to vibration for 10.79 yr, about a half of the FG workers could develop finger blanching. For the PG workers, the corresponding predicted latency was 5.02 yr. A discrepancy was found between the results from the ISO relationship and those from the cold provocation tests. A linear regression model was suggested employing vibration acceleration and vibration exposure time as explanatory variables for vascular dysfunction.

Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

PubMed Central

Griesbach, Grace S.; Ashley, Mark J.

2016-01-01

Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

PubMed

Cwik, Jan C; Sartory, Gudrun; Nuyken, Malte; Schürholt, Benjamin; Seitz, Rüdiger J

2017-09-01

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Agreeableness and alcohol-related aggression: the mediating effect of trait aggressivity.

PubMed

Miller, Cameron A; Parrott, Dominic J; Giancola, Peter R

2009-12-01

This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality.

Entitled vengeance: A meta-analysis relating narcissism to provoked aggression.

PubMed

Rasmussen, Kyler

2016-07-01

Narcissism has long been used to predict aggressive or vengeful responses to provocations from others. The strength of this relation can, however, vary widely from study to study. Narcissism and revenge were examined in 84 independent samples (N = 11297), along with the moderating role of sample type (i.e., child/adolescent, prisoner, undergraduate, or general samples), type of narcissism measure used (i.e., Narcissistic Personality Inventory, Psychological Entitlement Scale, Short D3, etc.), the nature of the provocation, and the type of provoked aggression examined. Narcissism was positively related to provoked aggression across studies (ρ = .25), but that relation was stronger in child/adolescent samples (ρ = .36) and when measures of entitlement or vulnerable narcissism were employed (ρ = .29). Implications for practical research, as well as neglected areas of research on narcissism and provoked aggression are discussed. Aggr. Behav. 42:362-379, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Nonconscious emotional activation colors first impressions: a regulatory role for conscious awareness.

PubMed

Lapate, Regina C; Rokers, Bas; Li, Tianyi; Davidson, Richard J

2014-02-01

Emotions can color people's attitudes toward unrelated objects in the environment. Existing evidence suggests that such emotional coloring is particularly strong when emotion-triggering information escapes conscious awareness. But is emotional reactivity stronger after nonconscious emotional provocation than after conscious emotional provocation, or does conscious processing specifically change the association between emotional reactivity and evaluations of unrelated objects? In this study, we independently indexed emotional reactivity and coloring as a function of emotional-stimulus awareness to disentangle these accounts. Specifically, we recorded skin-conductance responses to spiders and fearful faces, along with subsequent preferences for novel neutral faces during visually aware and unaware states. Fearful faces increased skin-conductance responses comparably in both stimulus-aware and stimulus-unaware conditions. Yet only when visual awareness was precluded did skin-conductance responses to fearful faces predict decreased likability of neutral faces. These findings suggest a regulatory role for conscious awareness in breaking otherwise automatic associations between physiological reactivity and evaluative emotional responses.

Artificial intelligence in predicting bladder cancer outcome: a comparison of neuro-fuzzy modeling and artificial neural networks.

PubMed

Catto, James W F; Linkens, Derek A; Abbod, Maysam F; Chen, Minyou; Burton, Julian L; Feeley, Kenneth M; Hamdy, Freddie C

2003-09-15

New techniques for the prediction of tumor behavior are needed, because statistical analysis has a poor accuracy and is not applicable to the individual. Artificial intelligence (AI) may provide these suitable methods. Whereas artificial neural networks (ANN), the best-studied form of AI, have been used successfully, its hidden networks remain an obstacle to its acceptance. Neuro-fuzzy modeling (NFM), another AI method, has a transparent functional layer and is without many of the drawbacks of ANN. We have compared the predictive accuracies of NFM, ANN, and traditional statistical methods, for the behavior of bladder cancer. Experimental molecular biomarkers, including p53 and the mismatch repair proteins, and conventional clinicopathological data were studied in a cohort of 109 patients with bladder cancer. For all three of the methods, models were produced to predict the presence and timing of a tumor relapse. Both methods of AI predicted relapse with an accuracy ranging from 88% to 95%. This was superior to statistical methods (71-77%; P < 0.0006). NFM appeared better than ANN at predicting the timing of relapse (P = 0.073). The use of AI can accurately predict cancer behavior. NFM has a similar or superior predictive accuracy to ANN. However, unlike the impenetrable "black-box" of a neural network, the rules of NFM are transparent, enabling validation from clinical knowledge and the manipulation of input variables to allow exploratory predictions. This technique could be used widely in a variety of areas of medicine.

Evaluation of canine adverse food reactions by patch testing with single proteins, single carbohydrates and commercial foods.

PubMed

Johansen, Cornelia; Mariani, Claire; Mueller, Ralf S

2017-10-01

Adverse food reaction (AFR) is an important differential diagnosis for the pruritic dog. It is usually diagnosed by feeding an elimination diet with a novel protein and carbohydrate source for eight weeks followed by subsequent food provocation. A previous study demonstrated that patch testing dogs with foods had a high sensitivity and negative predictability for selection of elimination diet ingredients. The aim of this study was to investigate patch testing with proteins, carbohydrates and dry commercial dog food in dogs to determine whether there was value in patch testing to aid the diagnosis of canine adverse food reaction. Twenty five privately owned dogs, with confirmed AFR, underwent provocation trials with selected food antigens and patch testing. For proteins, carbohydrates and dry dog food the sensitivity of patch testing was 100%, 70% and 22.2%, respectively; the negative predictive values of patch testing were 100%, 79% and 72%. The positive predictive values of patch testing for proteins and carbohydrates were 75% and 74%, respectively. This study confirmed that patch testing may be useful for the selection of a suitable protein source for an elimination diet in dogs with suspected AFR, but not as a diagnostic tool for canine AFR. Results for proteins are more reliable than for carbohydrates and the majority of positive patch test reactions were observed with raw protein. Patch testing with commercial dog food does not seem to be useful. © 2017 ESVD and ACVD.

Evaluation of the Houston biochemical relapse definition in men treated with prolonged neoadjuvant and adjuvant androgen ablation and assessment of follow-up lead-time bias.

PubMed

Pickles, Tom; Kim-Sing, Charmaine; Morris, W James; Tyldesley, Scott; Paltiel, Chuck

2003-09-01

To validate the Houston prostate-specific antigen relapse definition in a mature cohort of men treated with external beam radiotherapy (EBRT) and adjuvant androgen ablation (AA) and men treated with EBRT monotherapy, and to compare these results with the American Society for Therapeutic Radiology and Oncology (ASTRO) and Vancouver prostate-specific antigen relapse (biochemical no evidence of disease) definitions. A prospective database of 1490 men treated with EBRT, with or without AA, was examined. The impact on hazard proportions, as well as the predictive ability, of the Houston, ASTRO, and Vancouver definitions was tested. For all patients, the Houston definition was more accurate (79.5%) than the ASTRO (76.7%) or Vancouver (77.2%) definitions in predicting subsequent clinical relapse. The Houston definition was superior to the ASTRO definition in those treated both with and without AA and equivalent to the Vancouver definition in those receiving AA. The Houston definition demonstrated proportional hazards when categorized for the use of AA, unlike the ASTRO and Vancouver definitions. The effect of inadequate follow-up on the projected relapse rates was negligible with the Houston definition. The Houston relapse definition is favored after EBRT monotherapy or combined EBRT and AA. Use of the Cox proportional hazard multivariate analysis is appropriate with the Houston definition, but not with the ASTRO or Vancouver definitions if AA and non-AA patients are combined.

State anxiety modulates the return of fear.

PubMed

Kuhn, Manuel; Mertens, Gaetan; Lonsdorf, Tina B

2016-12-01

Current treatments for anxiety disorders are effective but limited by the high frequency of clinical relapse. Processes underlying relapse are thought to be experimentally modeled in fear conditioning experiments with return fear (ROF) inductions. Thereby reinstatement-induced ROF might be considered a model to study mechanisms underlying adversity-induced relapse. Previous studies have reported differential ROF (i.e. specific for the danger stimulus) but also generalized ROF (i.e. for safe and danger stimuli), but reasons for these divergent findings are not clear yet. Hence, the response pattern (i.e. differential or generalized) following reinstatement may be of importance for the prediction of risk or resilience for ROF. The aim of this study was to investigate state anxiety as a potential individual difference factor contributing to differentiability or generalization of return of fear. Thirty-six participants underwent instructed fear expression, extinction and ROF induction through reinstatement while physiological (skin conductance response, fear potentiated startle) and subjective measures of fear and US expectancy were acquired. Our data show that, as expected, high state anxious individuals show deficits in SCR discrimination between dangerous and safe cues after reinstatement induced ROF (i.e. generalization) as compared to low state anxious individuals. The ability to maintain discrimination under aversive circumstances is negatively associated with pathological anxiety and predictive of resilient responding while excessive generalization is a hallmark of anxiety disorders. Therefore, we suggest that experimentally induced ROF might prove useful in predicting relapse risk in clinical settings and might have implications for possible interventions for relapse prevention. Copyright © 2016 Elsevier B.V. All rights reserved.

A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children.

PubMed

Sutton, Rosemary; Venn, Nicola C; Law, Tamara; Boer, Judith M; Trahair, Toby N; Ng, Anthea; Den Boer, Monique L; Dissanayake, Anuruddhika; Giles, Jodie E; Dalzell, Pauline; Mayoh, Chelsea; Barbaric, Draga; Revesz, Tamas; Alvaro, Frank; Pieters, Rob; Haber, Michelle; Norris, Murray D; Schrappe, Martin; Dalla Pozza, Luciano; Marshall, Glenn M

2018-02-01

To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10 -5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL. © 2017 John Wiley & Sons Ltd.

Alcohol craving as a predictor of relapse.

PubMed

Schneekloth, Terry D; Biernacka, Joanna M; Hall-Flavin, Daniel K; Karpyak, Victor M; Frye, Mark A; Loukianova, Larissa L; Stevens, Susanna R; Drews, Maureen S; Geske, Jennifer R; Mrazek, David A

2012-11-01

Alcoholism treatment interventions, both psychosocial and pharmacologic, aim to reduce cravings to drink. Yet, the role of craving in treatment outcomes remains unclear. This study evaluated craving intensity measured with the Penn Alcohol Craving Scale (PACS) at admission and discharge from residential treatment as a predictive factor of relapse after treatment. The study cohort included 314 alcohol-dependent subjects. Associations between relapse after discharge, PACS score, and clinical variables were investigated using time-to-event analyses. The primary analysis, based on the intent-to-treat principle, presumed relapse in those declining follow-up or not responding to contact attempts. Secondary analysis utilized data from 226 subjects successfully contacted after discharge with a median follow-up time of 365 days. The intent-to-treat analysis demonstrated that relapse was associated with higher level of craving at admission (p= .002) and discharge (p < .001). The analysis of data from patients successfully contacted after discharge led to similar results. A multivariable analysis indicated that relapse rates increased as PACS scores increased, and a higher discharge PACS score was significantly associated with relapse (p= .006) even after adjusting for covariates. This study demonstrates that higher PACS scores at the time of admission and discharge are associated with relapse following residential addiction treatment. These data support the role of craving in relapse and the utility of craving measurement as a clinical guide in assessing relapse risk. Copyright © American Academy of Addiction Psychiatry.

Gender differences in trauma history and symptoms as predictors of relapse to alcohol and drug use.

PubMed

Heffner, Jaimee L; Blom, Thomas J; Anthenelli, Robert M

2011-01-01

The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol-dependent adults. Participants were 51 men (n = 24) and women (n = 27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular. © American Academy of Addiction Psychiatry.

Gender Differences in Trauma History and Symptoms as Predictors of Relapse to Alcohol and Drug Use

PubMed Central

Heffner, Jaimee L.; Blom, Thomas J.; Anthenelli, Robert M.

2011-01-01

The objective of this study was to determine whether there are gender-specific associations between trauma exposure and alcohol or drug relapse in alcohol dependent adults. Participants were 51 men (n=24) and women (n=27) with alcohol dependence, 22 (43.1%) of whom relapsed during study participation. Severity of childhood trauma; number of lifetime events evoking fear, helplessness, or horror; and current trauma symptoms all predicted relapse in women, but not in men. These findings highlight the importance of assessing trauma history and providing treatment of trauma-related symptoms for individuals with alcohol and drug dependence, and for women in particular. PMID:21679261

Claims-based proxies of patient instability among commercially insured adults with schizophrenia

PubMed Central

Ruetsch, Charles; Un, Hyong; Waters, Heidi C

2018-01-01

Objective Schizophrenia (Sz) patients are among the highest utilizers of hospital-based services. Prevention of relapse is in part a treatment goal in order to reduce hospital admissions. However, predicting relapse is a challenge, particularly for payers and disease management firms with only access to claims data. Understandably, such organizations have had little success predicting relapse. A tool that allows payers to identify patients at elevated risk of relapse could facilitate targeted interventions prior to relapse and avoid rehospitalization. In this study, a series of proxy measures of patient instability, calculated from claims data were examined for their utility in identifying Sz patients at elevated risk of relapse. Methods Aetna claims were used to assess the relationship between instability of Sz patients and valence and magnitude of antipsychotic (AP) medication change during a 2-year period. Six proxies of instability including hospital admissions, emergency department visits, medication utilization patterns, and use of outpatient services were identified. Results were replicated using claims data from Truven MarketScan®. Results Patients who switched AP ingredient had the highest overall instability at the point of switch and the second steepest decline in instability following switch. Those who changed to a long-acting injectable AP showed the second highest level of instability and the steepest decrease in instability following the change. Patients augmented with a second AP showed the smallest increase in instability, up to the switch. Results were directionally consistent between the two data sets. Conclusion Using claims-based proxy measures to estimate instability may provide a viable method to better understand Sz patient markers of change in disease severity. Also, such proxies could be used to identify those individuals with the greatest need for treatment modification preventing relapse, improving patient outcomes, and reducing the burden of illness. PMID:29765242

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

Relapse of incisor crowding: a visit to the Prince of Salina.

PubMed

López-Areal, Luis; Gandía, Jose-Luis

2013-03-01

The management of the retention period after comprehensive orthodontic treatment is of great importance, as a primary goal of clinician. Considerable controversy still surrounds the problem of stability after the retention period. Many studies analyze factors associated to the presence of crowding or incisor irregularity and find predictive features on its relapse. Most studies have reported little o no correlation between the treatment changes in the biological parameters - clinical, biometric (irregularity index, intermolar width, intercanine width, arch length, overjet, overbite), or cephalometric variables- that ocurred and the posttretament and postretention changes that may predict their future development. This article provides a bibliographical overview on the relapse of dental alignment in treated cases. In a brief historical introduction, the first studies on the long-term stability of orthodontic results are analysed. The article then goes on to assess studies that focus attention on anteroinferior alignment before finally studying relapse of upper crowding. It concludes by making some final comments in the light of the bibliography provided and the differents schools regarding retention needs and methods.

Validation study of the Japanese version of the Obsessive-Compulsive Drinking Scale.

PubMed

Tatsuzawa, Yasutaka; Yoshimasu, Haruo; Moriyama, Yasushi; Furusawa, Teruyuki; Yoshino, Aihide

2002-02-01

The Obsessive-Compulsive Drinking Scale (OCDS) is a self-rating questionnaire that measures cognitive and behavioral aspects of craving for alcohol. The OCDS consists of two subscales: the obsessive thoughts of drinking subscale (OS) and the compulsive drinking subscale (CS). This study aims to validate the Japanese version of the OCDS. First, internal consistency and discriminant validity were evaluated. Second, a prospective longitudinal 3-month outcome study of 67 patients with alcohol dependence who participated in a relapse prevention program was designed to assess the concurrent and predictive validity of the OCDS. The OCDS demonstrated high internal consistency. The OS had high discriminant validity, while the CS did not. Twenty-three patients (34.3%) dropped out of treatment. These patients had significantly higher OS scores than those who completed the program. At 3 months, the relapse group had significantly higher OCDS scores than the no relapse group. Also, the OCDS score was higher in subjects who had early-onset alcohol dependence than late-onset dependence. The OCDS is useful for evaluating cognitive aspect of craving and predicts dropout and relapse.

Cytomegalovirus (CMV) DNA load predicts relapsing CMV infection after solid organ transplantation.

PubMed

Sia, I G; Wilson, J A; Groettum, C M; Espy, M J; Smith, T F; Paya, C V

2000-02-01

Cytomegalovirus (CMV) DNA load was analyzed as a marker for relapse of CMV infection in 24 solid organ transplant patients with CMV infection or disease who received a fixed 14-day course of intravenous ganciclovir. Viral load was measured in blood samples obtained before and at the completion of treatment. Eight (33%) of 24 patients developed relapsing CMV infection. Median pretreatment viral loads were higher in the relapsing group (80,150 copies/106 leukocytes) than in the nonrelapsing group (5500 copies/106 leukocytes; P=.007). The relapsing group also had persistent detectable viral DNA (median, 5810 copies/106 leukocytes) after treatment, whereas it was undetectable in the nonrelapsing group (P<. 0001). Primary CMV infection (seronegative recipients of seropositive organs, D+R-) was an independent marker for CMV relapse (P=.03), and these patients had higher pre- and posttreatment viral loads than did non-D+/R- patients (P<.0001 and P=.0014, respectively). CMV DNA load is a useful marker for individualizing antiviral treatment of CMV infection in solid organ transplant recipients.

Religiousness and spirituality in patients with bipolar disorder.

PubMed

De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Giannini, Francesca; Jaén Moreno, Maria Jose; Moreno Díaz, Maria Josè; Medina León, Antonio; Segura-García, Cristina

2015-01-01

Religiousness and spirituality (R/S) are often neglected features among psychiatric patients but important both for quality of life and coping strategies for mental disorders. In patients affected by bipolar disorder (BD), R/S can sometimes be confused with symptoms related to the psychiatric disorder. This study aimed to perform a clinical review of the relationship between R/S and BD. Data sources included Medline (OvidSP), CINAHL (Ebsco), EMBASE (Ovid), PsychINFO (Ebsco), Angeline, Cochrane Database of Systematic Reviews and Database of Abstract of Reviews of Effects, searching for pertinent Keywords: 'religiousness', 'spirituality' and 'bipolar disorder'. Nine works were found but only five used homogeneous samples with BD patients. R/S were important when facing symptoms and relapses in the lifeworld. These beliefs influenced the relationship with psychiatrists and spiritual figures of reference. R/S play a role as a psychosocial variable in the course of BD. However, the hypothesis that the R/S factor can be relevant both in terms of providing a protective effect as well as a provocative element in depressive or hypomanic phases was not fully supported at the moment.

Ultra-long acting calcium channel blockers may decrease accuracy of the acetylcholine provocation test.

PubMed

Kurabayashi, Manabu; Asano, Mitsutoshi; Shimura, Tsukasa; Suzuki, Hidetoshi; Aoyagi, Hideshi; Yamauchi, Yasuteru; Okishige, Kaoru; Ashikaga, Takashi; Isobe, Mitsuaki

2017-06-01

When drug-induced coronary spasm provocation tests are performed, a washout period of >48h for calcium channel blockers (CCBs) is uniformly recommended. However, each CCB has a distinct half-life, and little is known about the influence of prior oral administration of CCBs on acetylcholine provocation test to evaluate coronary vasomotor reaction. We examined 245 consecutive patients with suspected vasospastic angina who had undergone acetylcholine provocation test. Of those patients, 29 patients had been on amlodipine, an ultra-long term acting CCB (group A), 34 on other CCBs (group O), and 182 patients on no CCB (group N). After CCBs had been withheld > 48h, we performed acetylcholine provocation, which resulted in 152 positive, 36 intermediate, and 57 negative reactions. We evaluated coronary artery tone calculated as follows: (luminal diameter after nitrate-baseline luminal diameter)÷(luminal diameter after nitrate)×100 (%). In group A patients, coronary artery tone was lower (A:9.1±6.9% vs. O:11.7±8.3% vs. N:12.1±8.5%, p=0.0011) and the positive rate of acetylcholine provocation test was lower than group O and group N (A:41% vs. O:68% vs. N:64%, p=0.047). Multivariate logistic analysis showed that taking amlodipine until 2days before acetylcholine provocation test was a significant inverse predictor for acetylcholine-provoked coronary spasm (odds ratio 0.327; 95% confidence interval 0.125-0.858, p=0.023). Residual vasodilatory effects of ultra-long acting CCB may decrease coronary artery tone and the vasoconstrictive reaction to acetylcholine suggesting that a 2-day pre-test drug holiday may not be long enough. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.

PubMed

Anzic, Srdjan Ante; Dzepina, Davor; Kalogjera, Livije

2007-11-01

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

Geographical variation in Plasmodium vivax relapse

PubMed Central

2014-01-01

Background Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission. Methods A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse. Results Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas. Conclusions The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations. PMID:24731298

Aggression in Children with Conduct Problems and Callous-Unemotional Traits: Social Information Processing and Response to Peer Provocation.

PubMed

Helseth, Sarah A; Waschbusch, Daniel A; King, Sara; Willoughby, Michael T

2015-11-01

Callous/unemotional traits (CU) moderate children's conduct problems (CP) in numerous domains, including social functioning. The present study examined whether CU traits also moderate the aggressiveness of children's social information processing (SIP) and responses to varying intensities of peer provocation. Sixty elementary school-age children (46 males) were grouped into those without CP or CU (controls, n = 32), those with CP but not CU (CP-only; n = 14), and those with both CP and CU (CPCU, n = 14). Participants completed a task that measured two aspects of SIP (response generation and hostile attribution bias) and a computerized reaction time task (CRTT) that measured behavior, affect, and communication before and after provocation under instrumental and hostile aggressive conditions. Children with CPCU generated more aggressive responses than controls on measures of SIP. On the CRTT, all children exhibited reactive aggression following high provocation, but only children with CPCU exhibited proactive aggression, and reactive aggression following low provocation; no differences in affect were found. In a series of exploratory analyses, CPCU children communicated antisocially, while CP-only communicated prosocially. Finally, children with CPCU did not seem to hold a grudge following the final instance of provocation, instead gradually returning to baseline like their non-CU peers. These distinct social cognitive and behavioral profiles hint at different etiologies of CP and CPCU, underscoring the variability of aggression in these populations.

Impact of smoking on the course of Graves' disease after withdrawal of antithyroid drugs.

PubMed

Quadbeck, B; Roggenbuck, U; Janssen, O E; Hahn, S; Mann, K; Hoermann, R

2006-09-01

Cigarette smoking has been reported to alter relapse rate in patients with Graves' disease (GD). However, the predictive effect of smoking in GD patients after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A prospective multicenter trial has previously identified smoking as an independent risk factor for relapse. Based on this study, the present paper gives a more detailed analysis of the impact of smoking on the long-term course of GD after ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later (visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs. 6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis showed a significantly higher relapse rate in smokers than non-smokers. A subset of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse during follow-up. Among them, smokers more often relapsed than non-smokers irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10 IU/L the predictive values of a positive and negative test for relapse was 68% and 73%, respectively (specificity 95%). In conclusion, we identified two effects by which smoking alters the course of GD. First, smoking is implicated to elevate TRAb levels and therefore increase the risk for relapse during follow-up. Second, smoking is an independent risk factor to worsen the clinical course of both, GD patients with low and high immunological risk to experience relapse after a successful outcome of ATDT. Thus, our data suggest that smoking has modifying immunological consequences and an adverse impact on the course of GD after withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.

Physical aggression as a function of perceived fighting ability and provocation: an experimental investigation.

PubMed

Archer, John; Benson, David

2008-01-01

In three studies, Resource Holding Power (RHP) and provocation were manipulated in scenarios involving a young person in a bar with friends. In Study 1, teenage men reported lower likelihood of responding with physical aggression when insulted as levels of three RHP cues (size, allies and reputation) increased, effects that were accentuated by combinations of high-RHP cues; in the second part of this study, they consistently rated an insult to their girlfriend as the most provoking from a range of possible provocations, chosen on theoretical and empirical grounds. Study 2 replicated the results of the first part of Study 1 in samples of men and women in their twenties, although the effects were weaker at low levels of RHP. Study 3 combined a high- or low-provoking event, with low, medium or high RHP, and a wider range of response choices. As expected, direct aggression increased as provocation increased and RHP decreased. Delayed aggressive responses, including revenge fantasies, were highest in response to high provocation and high RHP. Findings are discussed in relation to theoretical models of aggressive motivation. (c) 2007 Wiley-Liss, Inc.

Smoking cessation results in a clinical lung cancer screening program.

PubMed

Borondy Kitts, Andrea K; McKee, Andrea B; Regis, Shawn M; Wald, Christoph; Flacke, Sebastian; McKee, Brady J

2016-07-01

Lung cancer screening may provide a "teachable moment" for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012(®) high-risk criteria and had an order for CT lung screening. A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715-1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143-0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477-0.877). Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced relapse rates among smokers recently quit smoking.

Violent Recidivism: A Long-Time Follow-Up Study of Mentally Disordered Offenders

PubMed Central

Nilsson, Thomas; Wallinius, Märta; Gustavson, Christina; Anckarsäter, Henrik; Kerekes, Nóra

2011-01-01

Background In this prospective study, mentally disordered perpetrators of severe violent and/or sexual crimes were followed through official registers for 59 (range 8 to 73) months. The relapse rate in criminality was assessed, compared between offenders sentenced to prison versus forensic psychiatric care, and the predictive ability of various risk factors (criminological, clinical, and of structured assessment instruments) was investigated. Method One hundred perpetrators were consecutively assessed between 1998 and 2001 by a clinical battery of established instruments covering DSM-IV diagnoses, psychosocial background factors, and structured assessment instruments (HCR-20, PCL-R, and life-time aggression (LHA)). Follow-up data was collected from official registers for: (i) recidivistic crimes, (ii) crimes during ongoing sanction. Results Twenty subjects relapsed in violent criminality during ongoing sanctions (n = 6) or after discharge/parole (n = 14). Individuals in forensic psychiatric care spent significantly more time at liberty after discharge compared to those in prison, but showed significantly fewer relapses. Criminological (age at first conviction), and clinical (conduct disorder and substance abuse/dependence) risk factors, as well as scores on structured assessment instruments, were moderately associated with violent recidivism. Logistic regression analyses showed that the predictive ability of criminological risk factors versus clinical risk factors combined with scores from assessment instruments was comparable, with each set of variables managing to correctly classify about 80% of all individuals, but the only predictors that remained significant in multiple models were criminological (age at first conviction, and a history of substance abuse among primary relatives). Conclusions Only one in five relapsed into serious criminality, with significantly more relapses among subjects sentenced to prison as compared to forensic psychiatric care. Criminological risk factors tended to be the best predictors of violent relapses, while few synergies were seen when the risk factors were combined. Overall, the predictive validity of common risk factors for violent criminality was rather weak. PMID:22022445

Provocative Questions in Cancer: NCI Seminar

Cancer.gov

science writers' seminar to discuss various aspects of one of NCI’s signature efforts -- the Provocative Questions project. Discussion will focus on the scientific research that surrounds some of these questions.

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects

PubMed Central

Singhal, Neha; Praveen, V. P.; Bhavani, Nisha; Menon, Arun S.; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R. V.; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Context: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. Aim: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Subjects and Methods: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Statistical Analysis Used: Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Results: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). Conclusion: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease. PMID:27042408

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

PubMed

Singhal, Neha; Praveen, V P; Bhavani, Nisha; Menon, Arun S; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R V; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma

2016-01-01

Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

PubMed Central

Boelaert, Marleen; Matlashewski, Greg; Mondal, Dinesh; Arana, Byron; Kroeger, Axel; Olliaro, Piero

2016-01-01

Background As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. PMID:27490264

Predictors of relapses in ANCA-associated small vessel vasculitis with kidney involvement

PubMed Central

Iuliana, Andreiana; Simona, Stancu; Andreea, Avram; Ludmila, Taran; Gabriel, Mircescu

2014-01-01

Rationale: Almost half of the patients with anti-neutrophil cytoplasmic antibodies (ANCA) associated small vessel vasculitis relapse and their characteristics are still to be defined Objective: We aimed to evaluate the relapse rate and its determinants in a cohort of patients with ANCA associated vasculitis with severe kidney involvement. Methods and results: This is a retrospective study which included 100 patients consecutively admitted in a Nephrology Department with crescentic pauci-immune glomerulonephritis diagnosed by kidney biopsy. ANCAs were assessed by capture ELISA or indirect immunofluorescence (IFI). Patients were followed for a median period of 3.2 [0.1; 5.5] years. The median age was 61.6 years. The clinical condition at presentation was severe (median BVAS 16 and BVAS over 21 in one quarter of patients), mostly because of general, kidney and lung scores. Median creatinine was 5.7 mg/dL and 17% of the patients needed temporary dialysis. Eight patients relapsed (13.8%): one in the lung and seven in the kidney. The median time to relapse was 11.3 [9.2; 19.9] months. None of the investigated parameters allowed for differentiating patients who relapsed from those who did not, except higher hematuria in those who relapsed. Discussion: In our patients with ANCA vasculitis and severe kidney involvement, the relapse rate is low and hematuria but not ANCA specificity or clinical presentation allows the prediction of relapse. PMID:27057255

Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time.

PubMed

Kumar, S K; Dispenzieri, A; Fraser, R; Mingwei, F; Akpek, G; Cornell, R; Kharfan-Dabaja, M; Freytes, C; Hashmi, S; Hildebrandt, G; Holmberg, L; Kyle, R; Lazarus, H; Lee, C; Mikhael, J; Nishihori, T; Tay, J; Usmani, S; Vesole, D; Vij, R; Wirk, B; Krishnan, A; Gasparetto, C; Mark, T; Nieto, Y; Hari, P; D'Souza, A

2018-04-01

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.

Secondary central nervous system relapse in diffuse large B cell lymphoma in a resource limited country: result from the Thailand nationwide multi-institutional registry.

PubMed

Wudhikarn, Kitsada; Bunworasate, Udomsak; Julamanee, Jakrawadee; Lekhakula, Arnuparp; Chuncharunee, Suporn; Niparuck, Pimjai; Ekwattanakit, Supachai; Khuhapinant, Archrob; Norasetthada, Lalita; Nawarawong, Weerasak; Makruasi, Nisa; Kanitsap, Nonglak; Sirijerachai, Chittima; Chansung, Kanchana; Wong, Peerapon; Numbenjapon, Tontanai; Prayongratana, Kannadit; Suwanban, Tawatchai; Wongkhantee, Somchai; Praditsuktavorn, Pannee; Intragumtornchai, Tanin

2017-01-01

Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described. The 2-year cumulative incidence (CI) of SCNS relapse was 2.7 %. A total of 729, 1024, and 281 patients were classified as low-, intermediate-, and high-risk CNS international prognostic index (CNS-IPI) with corresponding 2-year CI of SCNS relapse of 1.5, 3.1, and 4.6 %, respectively (p < 0.001). Univariate analysis demonstrated advance stage disease, poor performance status, elevated lactate dehydrogenase, presence of B symptoms, more than one extranodal organ involvement, high IPI, and high CNS-IPI group as predictive factors for SCNS relapse. Rituximab exposure and intrathecal chemoprophylaxis offered no protective effect against SCNS relapse. At the time of analysis, six patients were alive. Median OS in SCNS relapsed patients was significantly shorter than relapsed patients without CNS involvement (13.2 vs 22.6 months) (p < 0.001). Primary causes of death were progressive disease (n = 35, 63.6 %) and infection (n = 9, 16.7 %). In conclusion, although the incidence of SCNS relapse in our cohort was low, the prognosis was dismal. Prophylaxis for SCNS involvement was underused even in high-risk patients. Novel approaches for SCNS relapse prophylaxis and managements are warranted.

Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status.

PubMed

Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D; Glass, Andrew; Vosburg, Suzanne K; Comer, Sandra D; Foltin, Richard W

2013-02-01

Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Study 1: data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal, and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n = 51; 10 ± 5 marijuana cigarettes/day) were enrolled. Study 2: to isolate the effects of cigarette smoking, marijuana intoxication, withdrawal, and relapse were assessed in daily marijuana and cigarette smokers (n = 15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU), and after at least 5 days without cigarettes (Quit). Study 1: 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (odds ratio: 19, p < .01). Individuals experiencing more positive subjective effects (i.e., feeling "high") after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p < .05). Study 2: most participants (>87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse, and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

PubMed

Garcia-Planella, Esther; Mañosa, Míriam; Chaparro, María; Beltrán, Belén; Barreiro-de-Acosta, Manuel; Gordillo, Jordi; Ricart, Elena; Bermejo, Fernando; García-Sánchez, Valle; Piqueras, Marta; Llaó, Jordina; Gisbert, Javier P; Cabré, Eduard; Domènech, Eugeni

2018-02-01

Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 μg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.

Predicting smoking relapse with a multidimensional versus a single-item tobacco craving measure.

PubMed

Berlin, Ivan; Singleton, Edward G; Heishman, Stephen J

2013-10-01

Research suggests that craving is a predictor of smoking relapse. Craving can be assessed by multiple item or multifactorial scales or by single items. However, no systematic comparisons of their prognostic validity or accuracy have been published. The French versions of the 12-item Tobacco Craving Questionnaire (FTCQ-12) and the single craving item on the Minnesota Nicotine Withdrawal Scale (MNWS) are brief, valid, and reliable self-report measures of tobacco craving. In this secondary study, we analyzed data from French smokers with health-related problems enrolled in the Adjustment of DOses of NIcotine in Smoking (ADONIS) cessation trial. We estimated prediction models for each measure and compared their ability to distinguish correctly participants who relapsed from those who did not at 1-8 weeks after their quit date. Adjusted for all potential confounders FTCQ-12 risk score (RS; Factor 2, Expectancy plus Factor 4, Purposefulness) and MNWS craving were valid predictors of smoking relapse at endpoints measured 1-7 weeks apart. Prognostic accuracy of FTCQ-12 RS was greatest at 1-2 weeks follow-up compared to only 1 week for MNWS craving. Sensitivity for FTCQ-12 RS and MNWS craving was 85% and 53%, respectively. FTCQ-12 RS suggests a relapse process involving urges and desires in anticipation of the positive benefits of smoking linked with intent and planning to smoke. Findings also suggest that FTCQ-12 RS may be a better predictor instrument for smoking relapse than MNWS craving. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impact of craving on alcohol relapse during, and 12 months following, outpatient treatment.

PubMed

Bottlender, Miriam; Soyka, Michael

2004-01-01

This study investigated the relationship between craving in abstinent alcohol-dependent patients measured by the Obsessive Compulsive Craving Scale (OCDS) (Anton et al., 1995) and relapse during and after completion of an intensive outpatient treatment programme. In a prospective study, participants were interviewed at entry to, and end of, an outpatient treatment programme, and 12 months after the end of the programme. To measuring craving the OCDS total score by Anton et al. (1995) and the three-factor model by Kranzler et al. (1999) were used. OCDS was administered at the beginning of treatment (when all patients were abstinent), and at the end of treatment in those who were abstinent and had completed the programme. Of 103 alcohol-dependent patients, 74 completed the treatment programme and at follow-up after 12 months 97% of these patients were personally re-interviewed. Thirty-two patients (31%) relapsed during the treatment phase. They had significantly higher craving measured by the total OCDS score and a significantly higher score on the subscales 'obsessions' and 'drinking control and consequences' compared to abstinent patients. Of the 74 patients who completed the programme 16% had a major relapse in the next 12 months. Major relapse was predicted by the total OCDS score and the subscale 'obsessions'. OCDS total score predicts relapse in outpatient treatment. Treatment and aftercare of patients with high craving should be intensified. In our study design, the subscales of the three-factor model by Kranzler et al. (1999) provided only little information gain compared to the OCDS total score.

Dysfunctional Default Mode Network in Methadone Treated Patients Who Have a Higher Heroin Relapse Risk.

PubMed

Li, Wei; Li, Qiang; Wang, Defeng; Xiao, Wei; Liu, Kai; Shi, Lin; Zhu, Jia; Li, Yongbin; Yan, Xuejiao; Chen, Jiajie; Ye, Jianjun; Li, Zhe; Wang, Yarong; Wang, Wei

2015-10-15

The purpose of this study was to identify whether heroin relapse is associated with changes in the functional connectivity of the default mode network (DMN) during methadone maintenance treatment (MMT). Resting-state functional magnetic resonance imaging (fMRI) data of chronic heroin relapsers (HR) (12 males, 1 female, age: 36.1 ± 6.9 years) and abstainers (HA) (11males, 2 female; age: 42.1 ± 8.1 years) were investigated with an independent component analysis to address the functional connectivity of their DMN. Group comparison was then performed between the relapsers and abstainers. Our study found that the left inferior temporal gyrus and the right superior occipital gyrus associated with DMN showed decreased functional connectivity in HR when compared with HA, while the left precuneus and the right middle cingulum had increased functional connectivity. Mean intensity signal, extracted from left inferior temporal gyrus of HR patients, showed a significant negative correlation corresponding to the degree of heroin relapse. These findings suggest that altered functional connectivity of DMN may contribute to the potential neurobiological mechanism(s) of heroin relapse and have a predictive value concerning heroin relapse under MMT.

Fear of food prospectively predicts drive for thinness in an eating disorder sample recently discharged from intensive treatment.

PubMed

Levinson, Cheri A; Brosof, Leigh C; Ma, Jackie; Fewell, Laura; Lenze, Eric J

2017-12-01

Fears of food are common in individuals with eating disorders and contribute to the high relapse rates. However, it is unknown how fears of food contribute to eating disorder symptoms across time, potentially contributing to an increased likelihood of relapse. Participants diagnosed with an eating disorder (N=168) who had recently completed intensive treatment were assessed after discharge and one month later regarding fear of food, eating disorder symptoms, anxiety sensitivity, and negative affect. Cross lagged path analysis was utilized to determine if fear of food predicted subsequent eating disorder symptoms one month later. Fear of food-specifically, anxiety about eating and feared concerns about eating-predicted drive for thinness, a core symptom domain of eating disorders. These relationships held while accounting for anxiety sensitivity and negative affect. There is a specific, direct relationship between anxiety about eating and feared concerns about eating and drive for thinness. Future research should test if interventions designed to target fear of food can decrease drive for thinness and thereby prevent relapse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tracing the origins of relapse in acute myeloid leukaemia to stem cells.

PubMed

Shlush, Liran I; Mitchell, Amanda; Heisler, Lawrence; Abelson, Sagi; Ng, Stanley W K; Trotman-Grant, Aaron; Medeiros, Jessie J F; Rao-Bhatia, Abilasha; Jaciw-Zurakowsky, Ivana; Marke, Rene; McLeod, Jessica L; Doedens, Monica; Bader, Gary; Voisin, Veronique; Xu, ChangJiang; McPherson, John D; Hudson, Thomas J; Wang, Jean C Y; Minden, Mark D; Dick, John E

2017-07-06

In acute myeloid leukaemia, long-term survival is poor as most patients relapse despite achieving remission. Historically, the failure of therapy has been thought to be due to mutations that produce drug resistance, possibly arising as a consequence of the mutagenic properties of chemotherapy drugs. However, other lines of evidence have pointed to the pre-existence of drug-resistant cells. For example, deep sequencing of paired diagnosis and relapse acute myeloid leukaemia samples has provided direct evidence that relapse in some cases is generated from minor genetic subclones present at diagnosis that survive chemotherapy, suggesting that resistant cells are generated by evolutionary processes before treatment and are selected by therapy. Nevertheless, the mechanisms of therapy failure and capacity for leukaemic regeneration remain obscure, as sequence analysis alone does not provide insight into the cell types that are fated to drive relapse. Although leukaemia stem cells have been linked to relapse owing to their dormancy and self-renewal properties, and leukaemia stem cell gene expression signatures are highly predictive of therapy failure, experimental studies have been primarily correlative and a role for leukaemia stem cells in acute myeloid leukaemia relapse has not been directly proved. Here, through combined genetic and functional analysis of purified subpopulations and xenografts from paired diagnosis/relapse samples, we identify therapy-resistant cells already present at diagnosis and two major patterns of relapse. In some cases, relapse originated from rare leukaemia stem cells with a haematopoietic stem/progenitor cell phenotype, while in other instances relapse developed from larger subclones of immunophenotypically committed leukaemia cells that retained strong stemness transcriptional signatures. The identification of distinct patterns of relapse should lead to improved methods for disease management and monitoring in acute myeloid leukaemia. Moreover, the shared functional and transcriptional stemness properties that underlie both cellular origins of relapse emphasize the importance of developing new therapeutic approaches that target stemness to prevent relapse.

Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males

PubMed Central

Dreher, Jean-Claude; Pazderska, Agnieszka; Frodl, Thomas; Nolan, John J.; O’Doherty, John P.

2016-01-01

Although popular discussion of testosterone’s influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males. PMID:27671627

MAOA-uVNTR genotype predicts interindividual differences in experimental aggressiveness as a function of the degree of provocation.

PubMed

Kuepper, Yvonne; Grant, Phillip; Wielpuetz, Catrin; Hennig, Juergen

2013-06-15

The MAOA-uVNTR has been suggested to play a role regarding aggression, however, results are inconsistent. We aimed at further elucidating potential effects of the MAOA-uVNTR on aggressiveness with respect to potential modulators: sex, experimental vs. trait aggressiveness and type of aggressiveness (proactive vs. reactive aggressiveness). We tested 239 healthy young adults (88 men/151 women). Participants were genotyped for the MAOA-uVNTR and performed a modified version of a competitive reaction time task - a commonly used and well established tool to elicit and measure aggressiveness. Furthermore, they completed a self-report scale measuring trait aggressiveness. We found a main effect of MAOA-uVNTR on a measure of reactive aggressiveness for both men and women, whereby the low-activity alleles of the MAOA-uVNTR were associated with substantially increased aggressive reactions (p<.05). This effect was unique for reactive aggressiveness. Measures of proactive aggressiveness or self reports were not associated with the MAOA-uVNTR-genotype. Our data are in line with earlier studies and indicate the MAOA-uVNTR-genotype to be specifically associated with measures of reactive impulsive experimental aggressiveness in healthy men and women. Furthermore the association between the MAOA-uVNTR genotype and aggressive responses increases in a fashion linear to the degree of provocation. This indicates that the low-functional alleles of the MAOA-uVNTR are not associated with increased aggressive behavior per se, but rather with an increased aggressive reactivity to provocation. Copyright © 2013 Elsevier B.V. All rights reserved.

Outcome of treatment after first relapse in younger adults with acute myeloid leukemia initially treated by the ALFA-9802 trial.

PubMed

Thomas, Xavier; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cécile; de Botton, Stéphane; de Revel, Thierry; Reman, Oumedaly; Terré, Christine; Gardin, Claude; Chelghoum, Youcef; Boissel, Nicolas; Quesnel, Bruno; Cordonnier, Catherine; Bourhis, Jean-Henri; Elhamri, Mohamed; Fenaux, Pierre; Preudhomme, Claude; Socié, Gérard; Michallet, Mauricette; Castaigne, Sylvie; Dombret, Hervé

2012-09-01

Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?

PubMed

Zingrillo, M; D'Aloiso, L; Ghiggi, M R; Di Cerbo, A; Chiodini, I; Torlontano, M; Liuzzi, A

1996-08-01

A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with 'burned-out' disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. Longitudinal prospective study of previously untreated patients with GD. Thirty-nine consecutive patients aged 10-72 years were treated with methimazole (MMI) for 12-24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2 +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.

Diagnostic testing of dogs for food hypersensitivity.

PubMed

Jeffers, J G; Shanley, K J; Meyer, E K

1991-01-15

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 4. Space motion sickness: symptoms, stimuli, and predictability

NASA Technical Reports Server (NTRS)

Oman, C. M.; Lichtenberg, B. K.; Money, K. E.; McCoy, R. K.

1986-01-01

Space sickness symptoms were observed by 4 specially trained observers on Spacelab-1. Three reported persistent symptoms, and vomited repeatedly during the first and/or second day of flight. Head movements on all axes were provocative, particularly in pitch and roll. Head acceleration data recorded from 2 symptomatic crewmen showed that after several hours of physical activity in orbit, symptoms appeared, and thereafter both crewmen were compelled to limit head movements. Firm body contact with motionless surfaces helped alleviate symptoms. When crewmembers floated into unfamiliar body orientations in the cabin, inherent ambiguities in static visual orientation cues sometimes produced spatial reorientation episodes which were also provocative. Symptoms largely resembled those of other forms of prolonged motion sickness, superimposed upon other symptoms attributable to fluid shift. All 4 eventually used anti-motion sickness drugs. When they did, vomiting frequency was reduced. By the 4th day, symptoms subsided, and head accelerations again increased in magnitude and variability. Sickness intensity in orbit was not predicted by statistically concordant results of 6 acute preflight susceptibility tests. However, results from a longer duration preflight prism goggles test showed an apparent correlation. All subjects were asymptomatic making head movements in parabolic flight 4 days after the mission, but not 1 year later. Overall, results support the view that space sickness is a motion sickness.

Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine, France.

PubMed

Debouverie, M

2009-11-15

We sought to identify (a) the change of incidence rates among gender from 1990 to 2002 from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort, and (b) the role of gender as a predictive demographic factor of disability during the initial course of the disease among multiple sclerosis (MS) patients. The incidence rates of multiple sclerosis (MS) in Lorraine, France, have significantly increased in women, but not in men, from 1990 to 2002 but this increase in incidence of MS was not related to a better ascertainment of patients with mild disability. A total of 2871 MS patients were analyzed. For relapsing-remitting (RR) patients, a multivariate analysis showed that a shorter time to the assignment of an EDSS score of 3 and 4 was associated with the late onset MS, incomplete recovery from the first relapse and a high number of relapses during the first 5 years after the MS onset. Median times were not influenced by gender or by time between the first two relapses. The data were very different for the time between the assignment of scores of 4 and 6, since the median times were not influenced by any of the predicting variables.

Effects on skin blood flow by provocation during local analgesia.

PubMed

Arildsson, M; Nilsson, G E; Strömberg, T

2000-01-01

Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45 degrees C, respectively, were applied for 9 s by use of a copper probe (O12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments. Copyright 2000 Academic Press.

Domestic Violence and Vagal Reactivity to Peer Provocation

PubMed Central

Katz, Lynn Fainsilber

2007-01-01

This paper examined whether individual differences in children’s vagal reactivity to peer provocation was related to domestic violence within the family. It also examined the question of whether conduct-problem children who show vagal augmentation to peer provocation come from families with high levels of domestic violence. During the peer provocation, children were expecting to interact with a difficult peer while vagal reactivity was assessed. Groups were divided into children who showed vagal augmentation and vagal suppression to the stressful peer interaction. Findings indicated that conduct-problem children who showed vagal augmentation to interpersonal challenge came from families with the highest levels of domestic violence. Vagal augmentation was also associated with a greater number of conduct-related problems for those children exposed to high levels of domestic violence. Discussion highlights the role of individual differences in physiological reactivity in understanding children’s behavior problems in relation to domestic violence. PMID:17118516

Perpetrators and targets of bullying at work: role stress and individual differences.

PubMed

Matthiesen, Stig Berge; Einarsen, Ståle

2007-01-01

A workplace survey study (N = 2215, response rate 47%) revealed that about 16% of the sample may be categorized as either perpetrators (5.4%), provocative victims (2.1%), or as targets of bullying (8.3%). Targets of bullying, provocative victims, and bullies were compared with those 84% who do not report any involvement with respect to bullying at work, self-esteem, aggressive tendencies, prior experiences of bullying, or experiences of role stress. Perpetrators were found to have a higher level of aggression than did the comparison group and the targets. Provocative victims manifested a low level of self-esteem and social competency combined with a high level of aggressiveness. Targets of bullying revealed low levels of self-esteem and social competency. Targets, provocative victims, and perpetrators reported elevated levels of role stress in the form of unclear or conflicting demands and expectations around work tasks and daily work.

Clinical tube weaning supported by hunger provocation in fully-tube-fed children.

PubMed

Hartdorff, Caroline M; Kneepkens, C M Frank; Stok-Akerboom, Anita M; van Dijk-Lokkart, Elisabeth M; Engels, Michelle A H; Kindermann, Angelika

2015-04-01

Children with congenital malformations, mental retardation, and complex early medical history frequently have feeding problems. Although tube feeding is effective in providing the necessary energy and nutrients, it decreases the child's motivation to eat and may lead to oral aversion. In this study, we sought to confirm our previous results, showing that a multidisciplinary clinical hunger provocation program may lead to quick resumption of oral feeding. In a crossover study, 22 children of 9 to 24 months of age who were fully dependent on tube feeding were randomly assigned to one of two groups: group A, intervention group (2-week multidisciplinary clinical hunger provocation program); and group B, control group (4-week outpatient treatment by the same multidisciplinary team). Patients failing one treatment were reassigned to the other treatment group. Primary outcome measures were at least 75% orally fed at the conclusion of the intervention and fully orally fed and gaining weight 6 months after the intervention. In group A, 9/11 patients were successfully weaned from tube feeding (2 failures: 1 developed ulcerative colitis, 1 drop-out). In group B, only 1 patient was weaned successfully; 10/11 were reassigned to the clinical hunger provocation program, all being weaned successfully. Six months after the intervention, 1 patient had to resume tube feeding. In total, in the control group, 1/11 (9%) was weaned successfully as compared with 18/21 (86%) in the hunger provocation group (P < 0.001). Multidisciplinary clinical hunger provocation is an effective short-term intervention for weaning young children from tube feeding.

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis.

PubMed

Bozkaya, Duygu; Livingston, Terrie; Migliaccio-Walle, Kristen; Odom, Tanner

2017-03-01

The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs. To compare the cost-effectiveness of current DMTs for patients with RRMS in the US. A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20 mg daily), and subcutaneous interferon beta-1a (IFN, 44 mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses. Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs. Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed). The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

PubMed

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse.

PubMed

Schmiegelow, K; Heyman, M; Gustafsson, G; Lausen, B; Wesenberg, F; Kristinsson, J; Vettenranta, K; Schroeder, H; Forestier, E; Rosthoej, S

2010-04-01

Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (>or=10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS(12y):0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient=0.65, P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than non-adolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

Measurable residual disease testing in acute myeloid leukaemia.

PubMed

Hourigan, C S; Gale, R P; Gormley, N J; Ossenkoppele, G J; Walter, R B

2017-07-01

There is considerable interest in developing techniques to detect and/or quantify remaining leukaemia cells termed measurable or, less precisely, minimal residual disease (MRD) in persons with acute myeloid leukaemia (AML) in complete remission defined by cytomorphological criteria. An important reason for AML MRD-testing is the possibility of estimating the likelihood (and timing) of leukaemia relapse. A perfect MRD-test would precisely quantify leukaemia cells biologically able and likely to cause leukaemia relapse within a defined interval. AML is genetically diverse and there is currently no uniform approach to detecting such cells. Several technologies focused on immune phenotype or cytogenetic and/or molecular abnormalities have been developed, each with advantages and disadvantages. Many studies report a positive MRD-test at diverse time points during AML therapy identifies persons with a higher risk of leukaemia relapse compared with those with a negative MRD-test even after adjusting for other prognostic and predictive variables. No MRD-test in AML has perfect sensitivity and specificity for relapse prediction at the cohort- or subject levels and there are substantial rates of false-positive and -negative tests. Despite these limitations, correlations between MRD-test results and relapse risk have generated interest in MRD-test result-directed therapy interventions. However, convincing proof that a specific intervention will reduce relapse risk in persons with a positive MRD-test is lacking and needs testing in randomized trials. Routine clinical use of MRD-testing requires further refinements and standardization/harmonization of assay platforms and results reporting. Such data are needed to determine whether results of MRD-testing can be used as a surrogate end point in AML therapy trials. This could make drug-testing more efficient and accelerate regulatory approvals. Although MRD-testing in AML has advanced substantially, much remains to be done.

Error-related brain activity predicts cocaine use after treatment at 3-month follow-up.

PubMed

Marhe, Reshmi; van de Wetering, Ben J M; Franken, Ingmar H A

2013-04-15

Relapse after treatment is one of the most important problems in drug dependency. Several studies suggest that lack of cognitive control is one of the causes of relapse. In this study, a relative new electrophysiologic index of cognitive control, the error-related negativity, is investigated to examine its suitability as a predictor of relapse. The error-related negativity was measured in 57 cocaine-dependent patients during their first week in detoxification treatment. Data from 49 participants were used to predict cocaine use at 3-month follow-up. Cocaine use at follow-up was measured by means of self-reported days of cocaine use in the last month verified by urine screening. A multiple hierarchical regression model was used to examine the predictive value of the error-related negativity while controlling for addiction severity and self-reported craving in the week before treatment. The error-related negativity was the only significant predictor in the model and added 7.4% of explained variance to the control variables, resulting in a total of 33.4% explained variance in the prediction of days of cocaine use at follow-up. A reduced error-related negativity measured during the first week of treatment was associated with more days of cocaine use at 3-month follow-up. Moreover, the error-related negativity was a stronger predictor of recent cocaine use than addiction severity and craving. These results suggest that underactive error-related brain activity might help to identify patients who are at risk of relapse as early as in the first week of detoxification treatment. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Is there a predictive value of EEG and MRI after a first afebrile seizure in children?

PubMed

Tews, W; Weise, S; Syrbe, S; Hirsch, W; Viehweger, A; Merkenschlager, A; Bertsche, A; Kiess, W; Bernhard, M K

2015-03-01

After a first afebrile seizure, EEG in addition to cMRI is recommended for pediatric patients. Once indications requiring immediate treatment are excluded, it is of interest to determine if the results provide a prognostic tool for seizure relapses. Patients aged between 1 month and 18 years who had a first afebrile seizure between 2006 and 2008 were retrospectively studied and monitored for another 48 months. Out of 248 patients, 62.5% had generalized and 36.3% focal seizures. 34.7% of the EEG results were pathological. 176 patients had a cMRI that showed in 23.3% probable epileptogenic lesions. 3 patients with benign cerebral tumours needed surgical therapy. In the following 48 months 29.4% of the children showed seizure relapses. There was a correlation between epileptic patterns in the EEG and further seizures (p=0.0001). However, the sensitivity of the EEG based diagnoses was 0.6, the specificity 0.78 and the positive predictive value 0.52. There was no correlation between epileptogenic lesions and the probability of seizure relapses. The sensitivity of the cMRI to this effect was 0.36, the specificity 0.74 and the positive predictive value 0.34. The EEG is superior to cMRI for predicting seizure relapses. The percentage of noticeable cMRI findings is high but this has low therapeutic relevance and is assumed to largely represent "incidental findings". It is important to question the value of MRI investigations for sedated small children except in the case of emergencies. The key question is whether the cMRI should be deployed to diagnose epilepsy, the probability of seizure recurrences or to classify the entity of a most likely epilepsy. © Georg Thieme Verlag KG Stuttgart · New York.

Refractory relapsing polychondritis: challenges and solutions

PubMed Central

Lekpa, Fernando Kemta; Chevalier, Xavier

2018-01-01

Relapsing polychondritis is a severe systemic immune-mediated disease characterized by an episodic and progressive inflammatory condition with progressive destruction of cartilaginous structures. This disease has for nearly a century kept secrets not yet explained. The real incidence and prevalence of this rare disease are unknown. The multiple clinical presentations and episodic nature of relapsing polychondritis cause a significant diagnosis delay. No guidelines for the management of patients with relapsing polychondritis have been validated to date. The challenges remain, both in the understanding of its pathophysiology and diagnosis, evaluation of its activity and prognosis, and its treatment. Possible solutions involve the sharing of data for relapsing polychondritis from worldwide reference centers. Thus, we would be able to evolve toward a better knowledge of its pathophysiology, the publication of new diagnosis criteria, which will include biological markers and imaging findings, the prediction of life-threatening or organ-threatening situations, and the publication of therapeutic evidence-based guidelines after performing at randomized controlled trials. PMID:29391837

Patients' Competence in and Performance of Cognitive Therapy Skills: Relation to the Reduction of Relapse Risk Following Treatment for Depression

ERIC Educational Resources Information Center

Strunk, Daniel R.; DeRubeis, Robert J.; Chiu, Angela W.; Alvarez, Jennifer

2007-01-01

Cognitive therapy (CT) for depression is designed to teach patients material that is believed to help prevent relapse following successful treatment. This study of 35 moderately to severely depressed patients who responded to CT provides the 1st evidence to suggest that both development and independent use of these competencies predict reduced…

Smoking cessation results in a clinical lung cancer screening program

PubMed Central

McKee, Andrea B.; Regis, Shawn M.; Wald, Christoph; Flacke, Sebastian; McKee, Brady J.

2016-01-01

Background Lung cancer screening may provide a “teachable moment” for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Methods Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012® high-risk criteria and had an order for CT lung screening. Results A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715–1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143–0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477–0.877). Conclusions Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced relapse rates among smokers recently quit smoking. PMID:27606076

Smokers can quit regardless of motivation stage in a worksite smoking cessation programme in Malaysia.

PubMed

Yasin, Siti Munira; Retneswari, Masilamani; Moy, Foong Ming; Koh, David; Isahak, Marzuki

2011-01-01

There is an unclear relationship between smoker's early motivation and success rates. Here we aimed to explore the correlates of motivation and smoking abstinence and relapse in worksite smoking cessation programmes. This prospective cohort study involved employees from two major public universities in Malaysia. Participants were actively recruited into a smoking cessation programme. At the start of treatment, participants were administered a questionnaire on sociodemographic variables, smoking habits and 'stage of change'. Behaviour therapy with free nicotine replacement therapy (NRT) was given as treatment for two months. A similar stage of change questionnaire was given at six months, and their smoking status was determined. There were 185 smokers from both Universities, who joined the programme. At six months, 24 smokers reported sustained abstinence while the others had relapsed. Prior to the programme, the majority of smokers were seriously planning on quitting (59.5%--preparation stage), but over a third had no plans to quit (35.5%--contemplation stage). There was no significant difference noted in changes of motivation stage among the relapsers and the non quitters. In addition, logistic regression showed that sustained abstinence was not predicted by pre-session motivation stage, but this did predict higher relapse for the participants, compared to those in the preparation stage. It is possible to help smokers in the lower motivation groups to quit, provided extra caution is taken to prevent relapse. Healthcare providers' recruitment strategies for cessation programmes should thus encompass smokers in all motivation stages.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

PubMed

Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

2011-09-15

Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us to report new sets of genes that according to their gene expression and physical interactions are predicted to be differentially expressed in MS versus healthy subjects, and in MS patients in relapse versus remission. Some of these genes may be useful biomarkers for diagnosing MS and predicting relapses in MS patients.

Methacholine challenge testing: improved patient comfort with a 2-tiered protocol.

PubMed

Segel, Michael J; Rabinovich, Einat; Schwarz, Yehuda; Ben-Dov, Issahar

2013-06-01

The methacholine challenge test (MCT) is a test of bronchial hyperreactivity used as an aid in the diagnosis of asthma. MCT results are reported as the provocation concentration at which the forced expiratory volume in 1 second (FEV1) decreases 20% (PC20). The requirement for a 20% or greater decrease in FEV1 results in precipitous decreases in FEV1 in some patients. To improve MCT safety without compromising accuracy. We performed a retrospective analysis of 879 consecutive MCTs (derivation cohort). A novel protocol for MCT was developed and validated in a cohort of 564 MCTs performed in a second institution. In comparison with a PC20 cutoff of less than 8 mg/mL, a provocation concentration at which the FEV1 decreases 10% (PC10) cutoff of 1 mg/mL or less has a sensitivity of 86%, a specificity of 98%, a positive predictive value (PPV) of 97%, and a negative predictive value (NPV) of 91%. We propose a novel 2-tiered protocol for MCT. If the PC10 is 1 mg/mL or less, bronchial hyperreactivity is present; if the PC10 is greater than 1 mg/mL, the test is continued until the provocative concentration is 8 mg/mL or a 20% decrease in FEV1 is achieved. Compared with the standard protocol, the proposed protocol has a sensitivity, specificity, PPV, NPV, and overall accuracy of 100%, 98%, 97.6%, 100%, and 99%, respectively. The modified protocol would have enabled us to avoid 26 of 42 cases (62%) in which a 40% or greater decrease in FEV1 occurred and would save 0.65 dose for every MCT performed. The 2-tiered protocol performed well in the validation cohort; sensitivity, specificity, PPV, NPV, and overall accuracy were 100%, 98%, 87%, 100%, and 98%, respectively. The proposed 2-tiered protocol is accurate, saves time, and avoids precipitous decreases in FEV1. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

ALLERGEN PROVOCATION AUGMENTS ENDOTOXIN-INDUCED NASAL INFLAMMATION IN ATOPIC ASTHMATICS

EPA Science Inventory

Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis.
Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenges in subjects with atopi...

Alcohol's effect on triggered displaced aggression.

PubMed

Aviles, Fredy; Earleywine, Mitchell; Pollock, Vicki; Stratton, Joy; Miller, Norman

2005-03-01

The authors examined alcohol's effect on triggered displaced aggression, the hostile reaction to a second provoking person after provocation from a first. Participants consumed an alcoholic or a nonalcoholic beverage. Subsequently, one individual provoked all of them with moderate intensity. Then, 2 groups were studied: those who received or who failed to receive a second provocation of minimal intensity. Consistent with prior research, participants who received a second, minimal provocation displayed more aggression than those who did not. After participants drank alcohol, the magnitude of this difference was significantly greater, indicating that alcohol increases triggered displaced aggression. Copyright (c) 2005 APA, all rights reserved.

Social provocation modulates decision making and feedback processing: Examining the trajectory of development in adolescent participants.

PubMed

Pincham, Hannah L; Wu, Claire; Killikelly, Clare; Vuillier, Laura; Fearon, R M Pasco

2015-10-01

Increasingly, research is turning to the ways in which social context impacts decision making and feedback processing in adolescents. The current study recorded electroencephalography to examine the trajectory of development across adolescence, with a focus on how social context impacts cognition and behaviour. To that end, younger (10-12 years) and older (14-16 years) adolescents played a modified Taylor Aggression Paradigm against two virtual opponents: a low-provoker and a high-provoker. During the task's decision phase (where participants select punishment for their opponent), we examined two event-related potentials: the N2 and the late positive potential (LPP). During the outcome phase (where participants experience win or loss feedback), we measured the feedback related negativity (FRN). Although N2 amplitudes did not vary with provocation, LPP amplitudes were enhanced under high provocation for the younger group, suggesting that emotional reactivity during the decision phase was heightened for early adolescents. During the outcome phase, the FRN was reduced following win outcomes under high provocation for both groups, suggesting that a highly provocative social opponent may influence the reward response. Collectively, the data argue that social context is an important factor modulating neural responses in adolescent behavioural and brain development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lymphocyte blastogenic responses to inciting food allergens in dogs with food hypersensitivity.

PubMed

Ishida, Rinei; Masuda, Kenichi; Kurata, Keigo; Ohno, Koichi; Tsujimoto, Hajime

2004-01-01

Lymphocyte blastogenic responses against food allergens in dogs with food hypersensitivity were evaluated in this study. Eleven dogs with food hypersensitivity, based on food elimination and oral food provocation tests and allergic responses to food allergens, were examined by various tests such as intradermal testing, antigen-specific IgE testing, and lymphocyte blastogenic responses. The number and kinds of food allergens identified as positive by these tests were compared with the offending food allergens that were found in an oral food provocation test. In 9 (82%) of the 11 dogs with food hypersensitivity, there was close agreement for positive allergens between the results of lymphocyte blastogenic responses and oral food provocation test; however, there was little agreement for intradermal and IgE testing of the positive allergens with those of the oral food provocation test (11% and 31%, respectively). In the 9 dogs, the stimulation indices of lymphocyte blastogenic responses increased to 2.0-10.1 upon food provocation but decreased significantly to 0.7-1.4 upon feeding the elimination diet until clinical signs disappeared. These results indicate that lymphocyte blastogenic responses may fluctuate because of exposure to offending food allergens in dogs with food hypersensitivity. Lymphocytes reactive to food allergens may play an important role in the pathogenesis of food hypersensitivity in dogs.

Oxytocin strengthens the link between provocation and aggression among low anxiety people.

PubMed

Pfundmair, Michaela; Reinelt, Annika; DeWall, C Nathan; Feldmann, Lisa

2018-07-01

Oxytocin (OT) not only modulates positive social interactions but also affects negative ones. Several studies have established a link between OT and aggression. However, they also resulted in an inconsistent picture and showed methodological issues. The current studies aimed to address these lacks and test the hypothesis that OT increases provocation-induced aggression in people low in anxiety. Therefore, two studies with 56 males (Study 1) as well as 40 females and 24 males (Study 2) were conducted. After responding to a trait anxiety questionnaire, participants self-administered OT or a placebo. Thereafter, provocation was manipulated by rejecting vs. accepting (Study 1) or insulting vs. accepting (Study 2) the participants by real human counterparts. Aggressive behavior was quantified by measuring how much hot sauce (Study 1) or unpleasant blasts of white noise (Study 2) participants delivered to their opponents, using two classic aggression paradigms. Both studies provided evidence that OT promotes aggression in response to provocation in low anxiety people which was not the case with no provocation or in high anxiety people. These findings confirm the idea that OT can be involved in the creation of aggressive behavior when accounting for situational and dispositional features. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictors of exercise relapse in a college population.

PubMed

Sullum, J; Clark, M M; King, T K

2000-01-01

Exercise improves physical and mental health. Nevertheless, most 20-year-olds do not exercise, and approximately 50% of the participants in exercise programs drop out in the first 3 to 6 months. In view of the health benefits of exercise, college health educators and clinicians need to be able to identify factors that predict exercise relapse in a student population. The authors administered questionnaires measuring Prochaska's 10 processes of change for exercise, self-efficacy, and decisional balance to 52 physically active undergraduate students. They assessed baseline exercise levels in October and reassessed them about 8 weeks later. At baseline, relapsers had significantly lower self-efficacy scores than those who maintained their exercise levels. The relapsers also had higher perceived negative views of exercise. These findings provide support for applying the transtheoretical model of behavioral change to a college population.

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

PubMed

Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

2018-05-02

Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clothing and Attributions Concerning Sexual Harassment.

ERIC Educational Resources Information Center

Johnson, Kim K. P.; Workman, Jane E.

1992-01-01

Photographs shown to 98 male and 102 female students illustrated provocative versus nonprovocative clothing on both men and women. Subjects rated provocative clothing more likely to induce sexual harassment. Females who had not experienced harassment rated those wearing nonprovocative clothing unlikely to be harassed. (SK)

Syphilis and neurosyphilis in a human immunodeficiency virus type-1 seropositive population: evidence for frequent serologic relapse after therapy.

PubMed

Malone, J L; Wallace, M R; Hendrick, B B; LaRocco, A; Tonon, E; Brodine, S K; Bowler, W A; Lavin, B S; Hawkins, R E; Oldfield, E C

1995-07-01

To describe clinical and treatment aspects of syphilis infection among patients seropositive for the human immunodeficiency virus (HIV). Results of serologic tests for syphilis, CD4+ T-lymphocyte counts, and clinical response to therapy were retrospectively monitored in 100 HIV-infected adults with syphilis from a tertiary-care military HIV program. Of the 1,206 HIV-infected patients, 100 (8.3%) in the cohort had syphilis; 61 patients were treated for active syphilis. Serologic or clinical relapse eventually occurred in 10 of the 56 treated patients (17.9%) with follow-up available; 7 of the 10 who relapsed had previously received high-dose intravenous or procaine penicillin therapy. Relapse occurred more than 12 months after initial therapy in 6 of 10 patients (60%) who experienced relapse; 5 patients experienced multiple relapses. The mean CD4+ T-lymphocyte count was not predictive of relapse. Patients with reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test titers (4 of 7 patients [57%]) or the rash of secondary syphilis (4 of 14 patients [29%]) were at highest risk of subsequent relapse or treatment failure when monitored for an average of 2 years. Standard penicillin regimens, including high-dose intravenous penicillin, transiently lowered serum VDRL titers in nearly all cases, but were sometimes inadequate in preventing serologic and clinical relapse in patients infected with HIV type-1, especially among those with secondary syphilis and reactive CSF VDRL titers. Careful long-term follow-up is essential, and repeated courses of therapy may be needed for patients infected with HIV type-1 who have syphilis.

Prognostic significance of cytogenetic abnormalities in patients with chronic myelogenous leukemia.

PubMed

Przepiorka, D; Thomas, E D

1988-03-01

The cytogenetic data for 126 patients with Ph-positive chronic myelogenous leukemia (CML) in accelerated phase or blast crisis were analysed for clonal chromosomal abnormalities in addition to the standard Ph prior to allogeneic or syngeneic bone marrow transplantation (BMT). Additional clonal abnormalities were found in 84%, and 14% had a variant Ph (VPh). In decreasing order of frequency, the most common clonal abnormalities were a second Ph, +8, i(17q), -Y and +19. A second Ph, VPh or +8 occurred more frequently in patients who relapsed following BMT than in those who survived disease-free for at least 1 1/2 years. The presence of an i(17q) alone did not correlate with relapse. The patients with a second Ph, VPh or +8 had a median time to relapse of 19 months, and the risk of relapse at 3 years was 73%. Those with other or no additional clonal abnormalities had not reached a median time to relapse and had a 3-year risk of relapse of 31% (p = 0.002). This analysis suggests that specific cytogenetic abnormalities may be useful indicators of resistance to therapy for CML and should be included in proportional hazard models to predict outcome after BMT.

The value and safety of specific nasal provocation in the diagnosis of allergic rhinitis in mild persistent asthma under inhaled steroid therapy.

PubMed

Tuskan, Tansu Cengiz; Gemicioglu, Bilun; Ikitimur, Hande; Yilmaz, Nail; Tuskan, Kemal; Oz, Ferhan; Can, Gunay

2010-01-01

Although specific nasal provocation is an objective diagnostic test for allergic rhinitis, it can also increase the lower airway responsiveness in asthmatic patients. Our goal was to determine the value and safety of specific nasal provocation test for the diagnosis of allergic rhinitis in mild persistent asthmatic patients under low-dose inhaled steroid therapy. The study was performed on 32 mild persistent, stable, mite-sensitive allergic asthmatics (group 1), 9 mild persistent nonallergic asthmatics (group 2) and 9 healthy non-smokers (group 3). Nasal symptoms were noted, paranasal sinus computerized tomography (PNCT) and rhinoscopic evaluations were performed. Cases with pathologic-anatomic changes in PNCT and rhinoscopy were excluded. Symptom scoring, flow-volume, peak expiratory flow (PEF), serum and nasal lavage eosinophil cationic protein (ECP) and nasal lavage eosinophil counts were performed before mite specific nasal provocation test and at the 0th, 4th and 24th hours following the test. No adverse effects were observed in all diagnostic procedures. Total diagnostic value of nasal symptoms were found to be at 92%, while being 70% for rhinoscopy and 88% for specific nasal provocation test respectively in the diagnosis of allergic rhinitis in group 1. Statistically significant differences were found between basal nasal lavage eosinophil values (p < 0.001) and ECP levels (p < 0.05) when group 1 was compared with both group 2 and group 3. In the remaining measured values between three groups, no statistically significant differences were found. Specific nasal provocation test is a safe method for mild house dust mite allergic asthma cases under low-dose inhaled steroid therapy, but history of rhinitis might be sufficient for the diagnosis of allergic rhinitis.

Histaminergic and cholinergic neuron systems in the impairment of human thermoregulation during motion sickness.

PubMed

Nobel, Gerard; Tribukait, Arne; Mekjavic, Igor B; Eiken, Ola

2010-05-31

Motion sickness (MS) exaggerates body cooling during cold-water immersion. The aim of the present study was to investigate whether such MS-induced predisposition to hypothermia is influenced by two anti-MS drugs: the histamine-receptor blocker dimenhydrinate (DMH) and the muscarine-receptor blocker scopolamine (Scop). Nine healthy male subjects were immersed in 15 degrees C water for a maximum of 90min in five conditions: (1) control (CN): no medication, no MS provocation; (2) MS-control (MS-CN): no medication, MS provocation; (3) MS-placebo (MS-P): placebo DMH and placebo Scop, MS provocation; (4) MS-DMH: DMH and placebo Scop, MS provocation; (5) MS-Scop: Scop and placebo DMH, MS provocation. MS was induced by use of a rotating chair. Throughout the experiments rectal temperature (T(re)), the difference in temperature between the non-immersed right forearm and third finger (T(ff)) as an index of peripheral vasoconstriction, and oxygen uptake (VO(2)) as a measure of shivering thermogenesis, were recorded. DMH and Scop were similarly efficacious in ameliorating nausea. The fall in T(re) was greater in the MS-CN and MS-P conditions than in the CN condition. DMH, but not Scop, prevented the MS-induced increase in body-core cooling. MS attenuated the cold-induced vasoconstriction, an effect which was fully prevented by DMH but only partially by Scop. MS provocation did not affect VO(2) in any condition. The results suggest that the MS-induced predisposition to hypothermia is predominantly mediated by histaminergic mechanisms and that DMH might be useful in conjunction with maritime accidents or other scenarios where exposure to cold and MS are imminent features. Copyright (c) 2010 Elsevier Inc. All rights reserved.

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

Does Tobacco-Control Mass Media Campaign Exposure Prevent Relapse Among Recent Quitters?

PubMed Central

Bowe, Steven J.; Durkin, Sarah J.; Yong, Hua-Hie; Spittal, Matthew J.; Simpson, Julie A.; Borland, Ron

2013-01-01

Objective: To determine whether greater mass media campaign exposure may assist recent quitters to avoid relapse. Method: Using date of data collection and postcode, media market estimates of televised tobacco-control advertising exposure measured by gross ratings points (GRPs) were merged with a replenished cohort study of 443 Australians who had quit in the past year. Participants’ demographic and smoking characteristics prior to quitting, and advertising exposure in the period after quitting, were used to predict relapse 1 year later. Results: In multivariate analysis, each increase in exposure of 100 GRPs (i.e., 1 anti-smoking advertisement) in the three-month period after the baseline quit was associated with a 5% increase in the odds of not smoking at follow-up (OR = 1.05, 95% CI 1.02–1.07, p < 0.001). This relationship was linear and unmodified by length of time quit prior to the baseline interview. At the mean value of 1081 GRPs in the 3 months after the baseline-quit interview, the predicted probability of being quit at follow-up was 52%, whereas it was 41% for the minimum (0) and 74% for the maximum (3,541) GRPs. Conclusion: Greater exposure to tobacco-control mass media campaigns may reduce the likelihood of relapse among recent quitters. PMID:22949574

Teens With Heavy Prenatal Cocaine Exposure Respond to Experimental Social Provocation with Escape Not Aggression

PubMed Central

Greenwald, M.K.; Chiodo, L.M.; Hannigan, J.H.; Sokol, R.J.; Janisse, J.; Delaney-Black, V.

2010-01-01

Preclinical data show that, compared to no exposure, prenatal cocaine exposure (PCE) has age-dependent effects on social interaction and aggression. The aim of this clinical study was to determine how heavy/persistent PCE – after controlling for other prenatal drug exposures, sex and postnatal factors – predicts behavioral sensitivity to provocation (i.e., reactive aggression) using a well-validated human laboratory model of aggression. African American teens (mean = 14.2 yrs old) with histories of heavy/persistent PCE (maternal cocaine use ≥ 2 times/week during pregnancy, or positive maternal or infant urine/meconium test at delivery; n = 86) or none/some exposure (NON: maternal cocaine use < 2 times/week during pregnancy; n = 330) completed the Point Subtraction Aggression Paradigm. In this task, teens competed in a computer game against a fictitious opponent. There were three possible responses: (a) earn points, to exchange for money later; or (b) “aggress” against the fictitious opponent by subtracting their points; or (c) escape temporarily from point subtraction perpetrated by the fictitious opponent. The PCE group responded significantly more frequently on the escape option than the NON group, but did not differ in aggressive or money-earning responses. These data indicate that PCE-teens provoked with a social stressor exhibit a behavioral preference for escape (negative reinforcement) more than for aggressive (retaliatory) or appetitive (point- or money-reinforced) responses. These findings are consistent with preclinical data showing that social provocation of adolescent or young adult offspring after PCE is associated with greater escape behavior, inferring greater submission, social withdrawal, or anxiety, as opposed to aggressive behavior. PMID:20600841

Testosterone reactivity to provocation mediates the effect of early intervention on aggressive behavior.

PubMed

Carré, Justin M; Iselin, Anne-Marie R; Welker, Keith M; Hariri, Ahmad R; Dodge, Kenneth A

2014-05-01

We tested the hypotheses that the Fast Track intervention program for high-risk children would reduce adult aggressive behavior and that this effect would be mediated by decreased testosterone responses to social provocation. Participants were a subsample of males from the full trial sample, who during kindergarten had been randomly assigned to the 10-year Fast Track intervention or to a control group. The Fast Track program attempted to develop children's social competencies through child social-cognitive and emotional-coping skills training, peer-relations coaching, academic tutoring, and classroom management, as well as training for parents to manage their child's behavior. At a mean age of 26 years, participants responded to laboratory provocations. Results indicated that, relative to control participants, men assigned to the intervention demonstrated reduced aggression and testosterone reactivity to social provocations. Moreover, reduced testosterone reactivity mediated the effect of intervention on aggressive behavior, which provides evidence for an enduring biological mechanism underlying the effect of early psychosocial intervention on aggressive behavior in adulthood.

Role of motivation to respond to provocation, the social environment, and trait aggression in alcohol-related aggression.

PubMed

Tremblay, Paul F; Mihic, Ljiljana; Graham, Kathryn; Jelley, Jennifer

2007-01-01

Little attention has been paid to the motivation to respond to provocation and to the interaction between this motivation, alcohol, the drinking environment, and individual characteristics. Undergraduates at six Canadian universities (N = 1,232) read three vignettes describing conflict situations with social environmental manipulations while imagining themselves as either sober or intoxicated. Self-ratings assessed likelihood of assertive and aggressive responses and motivational indices of anger, offensiveness of the instigator's actions, and importance to respond to the provocation. Respondents also completed a measure of trait aggression. Multi-group structural equation models supported the hypothesis that perceived likelihood of reactive aggression is influenced by perceived alcohol intoxication, gender, trait aggression, social environmental factors, and motivation to respond to the provocation. In addition, a number of interactions were found among the predictors. These results provide insight into the types of factors that may influence aggression in drinking situations. Copyright 2007 Wiley-Liss, Inc.

Neural stress reactivity relates to smoking outcomes and differentiates between mindfulness and cognitive-behavioral treatments.

PubMed

Kober, Hedy; Brewer, Judson A; Height, Keri L; Sinha, Rajita

2017-05-01

Stress and negative affect are known contributors to drug use and relapse, and several known treatments for addictions include strategies for managing them. In the current study, we administered a well-established stress provocation during functional magnetic resonance imaging (fMRI) to 23 participants who completed either mindfulness training (MT; N=11) or the American Lung Association's Freedom From Smoking (FFS; N=12), which is a cognitive-behavioral treatment (CBT) for smoking cessation. Across the entire sample, we found that stress reactivity in several brain regions including the amygdala and anterior/mid insula was related to reductions in smoking after treatment, as well as at 3-month post-treatment follow-up. Moreover, conjunction analysis revealed that these same regions also differentiated between treatment groups such that the MT group showed lower stress-reactivity compared to the FFS/CBT group. This suggests that reduction in stress reactivity may be one of the mechanisms that underlie the efficacy of MT in reducing smoking over time. The findings have important implications for our understanding of stress, the neural and psychological mechanisms that underlie mindfulness-based treatments, and for smoking cessation treatments more broadly. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic Avoidance Tendencies for Alcohol Cues Predict Drinking After Detoxification Treatment in Alcohol Dependence

PubMed Central

2016-01-01

Alcohol dependence is characterized by conflict between approach and avoidance motivational orientations for alcohol that operate in automatic and controlled processes. This article describes the first study to investigate the predictive validity of these motivational orientations for relapse to drinking after discharge from alcohol detoxification treatment in alcohol-dependent patients. One hundred twenty alcohol-dependent patients who were nearing the end of inpatient detoxification treatment completed measures of self-reported (Approach and Avoidance of Alcohol Questionnaire; AAAQ) and automatic (modified Stimulus-Response Compatibility task) approach and avoidance motivational orientations for alcohol. Their drinking behavior was assessed via telephone follow-ups at 2, 4, and 6 months after discharge from treatment. Results indicated that, after controlling for the severity of alcohol dependence, strong automatic avoidance tendencies for alcohol cues were predictive of higher percentage of heavy drinking days (PHDD) at 4-month (β = 0.22, 95% CI [0.07, 0.43]) and 6-month (β = 0.22, 95% CI [0.01, 0.42]) follow-ups. We failed to replicate previous demonstrations of the predictive validity of approach subscales of the AAAQ for relapse to drinking, and there were no significant predictors of PHDD at 2-month follow-up. In conclusion, strong automatic avoidance tendencies predicted relapse to drinking after inpatient detoxification treatment, but automatic approach tendencies and self-reported approach and avoidance tendencies were not predictive in this study. Our results extend previous findings and help to resolve ambiguities with earlier studies that investigated the roles of automatic and controlled cognitive processes in recovery from alcohol dependence. PMID:27935726

Isolating the Role of Psychological Dysfunction in Smoking Cessation Failure: Relations of Personality and Psychopathology to Attaining Smoking Cessation Milestones

PubMed Central

Leventhal, Adam M.; Japuntich, Sandra J.; Piper, Megan E.; Jorenby, Douglas E.; Schlam, Tanya R.; Baker, Timothy B.

2012-01-01

Research exploring psychological dysfunction as a predictor of smoking cessation success may be limited by nonoptimal predictor variables (i.e., categorical psychodiagnostic measures vs. continuous personality-based manifestations of dysfunction) and imprecise outcomes (i.e., summative point prevalence abstinence vs. constituent cessation milestone measures). Accordingly, this study evaluated the unique and overlapping relations of broad-spectrum personality traits (positive emotionality, negative emotionality, and constraint) and past-year psychopathology (anxiety, mood, and substance use disorder) to point prevalence abstinence and three smoking cessation milestones: (1) initiating abstinence; (2) first lapse; and (3) transition from lapse to relapse. Participants were daily smokers (N=1365) enrolled in a smoking cessation treatment study. In single predictor regression models, each manifestation of internalizing dysfunction (lower positive emotionality, higher negative emotionality, and anxiety and mood disorder) predicted failure at one or more cessation milestone. In simultaneous predictor models, lower positive and higher negative emotionality significantly predicted failure to achieve milestones after controlling for psychopathology. Psychopathology did not predict any outcome when controlling for personality. Negative emotionality showed the most robust and consistent effects, significantly predicting failure to initiate abstinence, earlier lapse, and lower point prevalence abstinence rates. Substance use disorder and constraint did not predict cessation outcomes, and no single variable predicted lapse-to-relapse transition. These findings suggest that personality-related manifestations of internalizing dysfunction are more accurate markers of affective sources of relapse risk than mood and anxiety disorders. Further, individuals with high trait negative emotionality may require intensive intervention to promote the initiation and early maintenance of abstinence. PMID:22642858

Human Correlates of Provocative Questions in Pancreatic Pathology

PubMed Central

McDonald, Oliver G.; Maitra, Anirban; Hruban, Ralph H.

2012-01-01

Studies of cell lines and of animal models of pancreatic cancer have raised a number of provocative questions about the nature and origins of human pancreatic cancer and have provided several leads into exciting new approaches for the treatment of this deadly cancer. In addition, clinicians with little or no contact with human pathology have challenged the way that pancreatic pathology is practiced, suggesting that “genetic signals” may be more accurate than today’s multi-modal approach to diagnoses. In this review we consider eight provocative issues in pancreas pathology, with an emphasis on “the evidence derived from man.” PMID:23060061

Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence.

PubMed

Wojnar, Marcin; Brower, Kirk J; Strobbe, Stephen; Ilgen, Mark; Matsumoto, Halina; Nowosad, Izabela; Sliwerska, Elzbieta; Burmeister, Margit

2009-04-01

The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger. The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

Association between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

PubMed Central

Wojnar, Marcin; Brower, Kirk J.; Strobbe, Stephen; Ilgen, Mark; Matsumoto, Halina; Nowosad, Izabela; Sliwerska, Elzbieta; Burmeister, Margit

2009-01-01

Background The purpose of this study was to examine relationships between genetic markers of central serotonin and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. Methods The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately one year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. Results Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse (OR = 2.62; p = 0.019), and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (HR = 4.93, p = 0.001) were even stronger. Conclusions The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies. PMID:19170664

Significance of definitions of relapse after discontinuation of oral antivirals in HBeAg-negative chronic hepatitis B.

PubMed

Papatheodoridis, George V; Manolakopoulos, Spilios; Su, Tung-Hung; Siakavellas, Spyros; Liu, Chun-Jen; Kourikou, Anastasia; Yang, Hung-Chih; Kao, Jia-Horng

2017-08-31

Relapses are observed in most hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long-term NA therapy. In total, 130 HBeAg-negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on-therapy virological remission for ≥24 months and close follow-up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on-therapy virological remission was 43 months. During a median off-NAs follow-up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%-49%, 4%-73%, 11%-82%, and 16%-90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. In HBeAg-negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off-NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off-NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (Hepatology 2017). © 2017 by the American Association for the Study of Liver Diseases.

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

PubMed

Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

2016-07-01

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study.

PubMed

Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Bouadballah, R; Radford, J; Bargetzi, M; Ribrag, V; Dührsen, U; Ma, D; Briere, J; Thieblemont, C; Bachy, E; Moskowitz, C H; Glass, B; Gisselbrecht, C

2017-02-01

In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.

Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males

PubMed Central

Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

2018-01-01

Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status–seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants’ choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se. In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone. PMID:29551966

Emotional reactivity to threat modulates activity in mentalizing network during aggression.

PubMed

Beyer, Frederike; Münte, Thomas F; Erdmann, Christian; Krämer, Ulrike M

2014-10-01

Aggression is a common response to provocation, albeit with considerable interindividual differences. In this fMRI study, we investigated emotional reactivity to threat as possible link between provocation and aggression, as well as the neural correlates of this relationship. We hypothesized that emotional reactivity, measured as fear potentiation (FP) of the startle response, would be negatively associated with aggressive behavior and would modulate neural activity during an aggressive interaction. In 30 healthy female participants, FP was measured as the difference between blink amplitudes while watching threatening vs neutral pictures. Participants subsequently engaged in a variant of the Taylor Aggression Paradigm (TAP), while being scanned. During the TAP, participants selected a punishment level for either a highly provoking or a nonprovoking opponent. There was no difference in aggressive behavior between participants high and low in FP. However, we found a negative correlation between FP and the neural provocation effect in several regions of a network previously associated with mentalizing including the medial prefrontal cortex, precuneus and the temporo-parietal junction. Independently of the FP variability, aggressive behavior correlated with the provocation effect on activity in the caudate nucleus. Our results indicate that during a provocative confrontation, high emotional reactivity to threat suppresses recruitment of the mentalizing network. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males.

PubMed

Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

2018-01-01

Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status-seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants' choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se . In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

Discontinuation of Buprenorphine Maintenance Therapy: Perspectives and Outcomes

PubMed Central

Bentzley, Brandon S.; Barth, Kelly S.; Back, Sudie E.; Book, Sarah W.

2015-01-01

Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers’ or patients’ reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation. PMID:25601365

Peer Provocation in Physical Education: Experiences of Botswana Adolescents

ERIC Educational Resources Information Center

Shehu, Jimoh

2009-01-01

Critical incidents of peer provocation in physical education were investigated among 675 junior secondary school students in Botswana. Data were generated through a brief, open-ended questionnaire requesting the students to narrate their experiences of bad, hurtful and offensive peer behaviours during physical education classes. Six overlapping…

78 FR 48216 - Culturally Significant Objects Imported for Exhibition Determinations: “Balthus: Cats and Girls...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-07

... DEPARTMENT OF STATE [Public Notice 8410] Culturally Significant Objects Imported for Exhibition Determinations: ``Balthus: Cats and Girls--Paintings and Provocations'' SUMMARY: Notice is hereby given of the... that the objects to be included in the exhibition ``Balthus: Cats and Girls--Paintings and Provocations...

Time to relapse following treatment for methamphetamine use: a long-term perspective on patterns and predictors.

PubMed

Brecht, Mary-Lynn; Herbeck, Diane

2014-06-01

This paper describes methamphetamine (MA) use patterns, specifically the duration of continuing abstinence ("time to relapse") for periods averaging 5 years post-discharge from treatment for MA use, and the relationship with selected user and treatment characteristics. A sample of 350 treatment admissions from a large county substance use disorder (SUD) treatment system was randomly selected (within gender, race/ethnicity, treatment modality strata). Retrospective self-report data are from natural history interviews (NHI) conducted approximately 3 years after treatment and a follow-up of 2-3 years later. Relapse is defined as any use of MA with time as the number of months of continuous MA abstinence after treatment discharge until relapse. This outcome was constructed from a monthly MA use timeline using NHI data. A Cox model was used to examine time to relapse and predictors. Sixty-one percent of the sample relapsed to MA use within 1 year after treatment discharge and 14% during years 2-5. Significant protective factors predicting longer time to relapse included having experienced serious MA-related psychiatric/behavioral problems (hazard ratio [HR]=0.75, p=0.027), longer duration of the index treatment episode (HR=0.93, p=0.001), and participating in self-help or other treatment during the post-treatment abstinence period (HR=0.29, p<0.001); risk factors for shorter time to relapse included having a parent with alcohol and/or drug use problems (HR=1.35, p=0.020) and involvement in MA sales (HR=1.48, p=0.002). Results contribute a long-term perspective on patterns of MA use following treatment and support a need for early post-treatment and long-term continuing care and relapse-prevention services. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

PubMed

Radujkovic, Aleksandar; Guglielmi, Cesare; Bergantini, Stefania; Iacobelli, Simona; van Biezen, Anja; Milojkovic, Dragana; Gratwohl, Alois; Schattenberg, Antonius V M B; Verdonck, Leo F; Niederwieser, Dietger W; de Witte, Theo; Kröger, Nicolaus; Olavarria, Eduardo

2015-07-01

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pharmacological Strategies in the Prevention of Relapse Following Electroconvulsive Therapy

PubMed Central

Prudic, Joan; Haskett, Roger; McCall, W. Vaughn; Isenberg, Keith; Cooper, Thomas; Rosenquist, Peter B.; Mulsant, Benoit H.; Sackeim, Harold A.

2012-01-01

Objective To determine whether starting antidepressant medication at the start of ECT reduces postECT relapse and to determine whether continuation pharmacotherapy with nortriptyline and lithium (NT-Li) differs in efficacy or side effects from continuation pharmacotherapy with venlafaxine and lithium (VEN-Li). Method During an acute ECT phase, 319 patients were randomized to treatment with moderate dosage bilateral ECT or high dosage right unilateral ECT. They were also randomized to concurrent treatment with placebo, NT, or VEN. Of 181 patients to meet postECT remission criteria, 122 (67.4%) participated in a second continuation pharmacotherapy phase. Patients earlier randomized to NT or VEN continued on the antidepressant, while patients earlier randomized to placebo were now randomized to NT or VEN. Li was added for all patients who were followed until relapse or 6 months. Results Starting an antidepressant medication at the beginning of the ECT course did not impact on the rate or timing of relapse relative to starting pharmacotherapy after ECT completion. The combination of NT-Li did not differ from VEN-Li in any relapse or side effect measure. Older age was strongly associated with lower relapse risk, whereas the type of ECT administered in the acute phase and medication resistance were not predictive. Across sites, 50% of patients relapsed, 33.6% continued in remission 6 months postECT, and 16.4% dropped out. Conclusions Starting an antidepressant medication during ECT does not impact relapse and there are concerns about administering Li during an acute ECT course. Nortriptyline and venlafaxine were equally effective in prolonging remission, although relapse rates following ECT are substantial despite intensive pharmacology. As opposed to the usual abrupt cessation of ECT, the impact of an ECT taper should be evaluated. PMID:23303417

Transient impairment of olfactory threshold in acute multiple sclerosis relapse.

PubMed

Bsteh, Gabriel; Hegen, Harald; Ladstätter, Felix; Berek, Klaus; Amprosi, Matthias; Wurth, Sebastian; Auer, Michael; Di Pauli, Franziska; Deisenhammer, Florian; Lutterotti, Andreas; Berger, Thomas

2018-05-18

Impairment of olfactory threshold is a feature of early and active relapsing remitting multiple sclerosis (RRMS). It predicts inflammatory disease activity and was reported to be transient. However, the timing of onset and resolve of olfactory threshold impairment remains unclear. To prospectively assess the development of olfactory threshold in acute MS relapse over time in comparison to stable MS patients. In a prospective observational design, we measured olfactory threshold by performing the Sniffin' Sticks test (minimum score 0, maximum score 16 reflecting optimal olfactory function) at baseline and after 4, 12 and 24 weeks. We included 30 RRMS patients with acute MS relapse and 30 clinically stable RRMS patients (defined as no relapse within the last 12 months) as a control group. Olfactory threshold was impaired in patients with acute MS relapse at baseline (median difference = -3.5; inter-quartile range [IQR] -4.5- - 2.5; p < 0.001), week 4 (-2.5; IQR -3.0 - -2.0; p < 0.001), week 12 (-1.5; IQR -2.0 - -0.5; p = 0.002) and week 24 (-0.5; IQR -1.0 - 0.0; p = 0.159) compared to stable MS patients. Of note, in relapsing patients in whom disease-modifying treatment was initiated or escalated after relapse, threshold did not differ anymore from stable patients at week 12 (-0.5; IQR -1.0 - 0.5; p = 0.247) and week 24 (0.0; IQR -1.0 - 1.0; p = 0.753). Olfactory threshold impairment seems to be a transient bystander feature of MS relapse. It may be correlated to the level of inflammation within the CNS and might be a useful biomarker in this regard. Copyright © 2018 Elsevier B.V. All rights reserved.

Prediction of the space adaptation syndrome

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Homick, J. L.; Ryan, P.; Moseley, E. C.

1984-01-01

The univariate and multivariate relationships of provocative measures used to produce motion sickness symptoms were described. Normative subjects were used to develop and cross-validate sets of linear equations that optimally predict motion sickness in parabolic flights. The possibility of reducing the number of measurements required for prediction was assessed. After describing the variables verbally and statistically for 159 subjects, a factor analysis of 27 variables was completed to improve understanding of the relationships between variables and to reduce the number of measures for prediction purposes. The results of this analysis show that none of variables are significantly related to the responses to parabolic flights. A set of variables was selected to predict responses to KC-135 flights. A series of discriminant analyses were completed. Results indicate that low, moderate, or severe susceptibility could be correctly predicted 64 percent and 53 percent of the time on original and cross-validation samples, respectively. Both the factor analysis and the discriminant analysis provided no basis for reducing the number of tests.

Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.

PubMed

Park, Sunhee; Abdi, Tsion; Gentry, Mark; Laine, Loren

2016-12-01

Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission. Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present. Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission at baseline. UC patients with histological remission have a significant 52% RR reduction in clinical relapse/exacerbation compared with those with histological activity. Histological remission is also superior to endoscopic and clinical remission in predicting clinical outcomes. As ~30% of patients with endoscopic and clinical remission still have histological activity, addition of histological status as an end point in clinical trials or practice has the potential to improve clinical outcomes.

Clinical utility of host genetic IL-28B variants in hepatitis C virus genotype 1 Asian patients retreated with pegylated interferon plus ribavirin.

PubMed

Huang, Chung-Feng; Yeh, Ming-Lun; Hsieh, Meng-Hsuan; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Wang, Liang-Yen; Huang, Jee-Fu; Juo, Suh-Hang Hank; Lin, Yi-Ching; Dai, Chia-Yen; Chuang, Wan-Long; Yu, Ming-Lung

2013-09-01

Host interleukin-28B (IL-28B) genetic variants determine a sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) treatment-naïve patients. Its impact on treatment-experienced Asian patients with peginterferon/ribavirin in is to be elucidated. IL-28B rs8099917 genotype was determined in 70 HCV-1 treatment-experienced patients retreated with 48-week peginterferon/ribavirin. The SVR rate was 60.0% and was significantly higher in previous relapsers than in nonresponders (72.7% and 13.3%, P < 0.001). Multivariate analysis revealed that the most important factor predictive of an SVR was previous relapse (Odds ratio [OR]/95% confidence interval [CI]: 14.76/2.72-80.06, P = 0.002), followed by the carriage of rs8099917 TT genotype (OR/95% C.I.: 7.67/1.27-46.49, P = 0.03). Comparing to patients with TG/GG genotype, those with TT genotype had significantly higher rates of rapid virological response (29.3% vs 0%, P = 0.03), end-of-treatment virological response (86.2% vs 50.0%, P = 0.01), SVR (69.0% vs 16.7%, P = 0.002), and lower relapse rate (22.0 % vs 66.7%, P = 0.04). The SVR rate was similarly low between previous nonresponders with different rs8099917 genotypes (12.5% vs 14.3%, P = 1). On the contrary, previous relapsers with rs8099917 TT genotype had a significantly higher SVR rate than those who carried rs8099917 TG/GG genotype (78.0 % vs 20.0%, P = 0.02). Stepwise logistic regression analysis revealed that the only factor predictive of an SVR in previous relapsers was the carriage of rs809997 TT genotype (OR/95% CI:18.50/1.82-188.39, P = 0.014). Host IL-28B genetic variants played a role in Asian relapsers but not nonresponders retreated with peginterferon/ribavirin. Direct antiviral agents might be possibly avoidable in Asian relapsers with favorable IL-28B genotype. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Treatment outcome and patterns of relapse following adjuvant carboplatin for stage I testicular seminomatous germ-cell tumour: results from a 17-year UK experience.

PubMed

Chau, C; Cathomas, R; Wheater, M; Klingbiel, D; Fehr, M; Bennett, J; Markham, H; Lee, C; Crabb, S J; Geldart, T

2015-09-01

Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%-5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4-214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5-109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A Case of Cardiac Cephalalgia Showing Reversible Coronary Vasospasm on Coronary Angiogram

PubMed Central

Yang, YoungSoon; Jin, Dong Gyu; Jang, Il Mi; Jang, YoungHee; Na, Hae Ri; Kim, SanYun

2010-01-01

Background Under certain conditions, exertional headaches may reflect coronary ischemia. Case Report A 44-year-old woman developed intermittent exercise-induced headaches with chest tightness over a period of 10 months. Cardiac catheterization followed by acetylcholine provocation demonstrated a right coronary artery spasm with chest tightness, headache, and ischemic effect of continuous electrocardiography changes. The patient's headache disappeared following intra-arterial nitroglycerine injection. Conclusions A coronary angiogram with provocation study revealed variant angina and cardiac cephalalgia, as per the International Classification of Headache Disorders (code 10.6). We report herein a patient with cardiac cephalalgia that manifested as reversible coronary vasospasm following an acetylcholine provocation test. PMID:20607049

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

PubMed

Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

1996-07-01

To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

Self-regulatory failure and intimate partner violence perpetration.

PubMed

Finkel, Eli J; DeWall, C Nathan; Slotter, Erica B; Oaten, Megan; Foshee, Vangie A

2009-09-01

Five studies tested the hypothesis that self-regulatory failure is an important predictor of intimate partner violence (IPV) perpetration. Study 1 participants were far more likely to experience a violent impulse during conflictual interaction with their romantic partner than they were to enact a violent behavior, suggesting that self-regulatory processes help individuals refrain from perpetrating IPV when they experience a violent impulse. Study 2 participants high in dispositional self-control were less likely to perpetrate IPV, in both cross-sectional and residualized-lagged analyses, than were participants low in dispositional self-control. Study 3 participants verbalized more IPV-related cognitions if they responded immediately to partner provocations than if they responded after a 10-s delay. Study 4 participants whose self-regulatory resources were experimentally depleted were more violent in response to partner provocation (but not when unprovoked) than were nondepleted participants. Finally, Study 5 participants whose self-regulatory resources were experimentally bolstered via a 2-week training regimen exhibited less violent inclinations than did participants whose self-regulatory resources had not been bolstered. These findings hint at the power of incorporating self-regulation dynamics into predictive models of IPV perpetration. (c) 2009 APA, all rights reserved).

Proton Magnetic Resonance Spectroscopic Imaging in Newly Diagnosed Glioblastoma: Predictive Value for the Site of Postradiotherapy Relapse in a Prospective Longitudinal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laprie, Anne; Laboratory of Biophysics and Medical Imaging, Universite Toulouse III Paul Sabatier, Toulouse; Catalaa, Isabelle

Purpose: To investigate the association between magnetic resonance spectroscopic imaging (MRSI)-defined, metabolically abnormal tumor regions and subsequent sites of relapse in data from patients treated with radiotherapy (RT) in a prospective clinical trial. Methods and Materials: Twenty-three examinations were performed prospectively for 9 patients with newly diagnosed glioblastoma multiforme studied in a Phase I trial combining Tipifarnib and RT. The patients underwent magnetic resonance imaging (MRI) and MRSI before treatment and every 2 months until relapse. The MRSI data were categorized by the choline (Cho)/N-acetyl-aspartate (NAA) ratio (CNR) as a measure of spectroscopic abnormality. CNRs corresponding to T1 and T2more » MRI for 1,207 voxels were evaluated before RT and at recurrence. Results: Before treatment, areas of CNR2 (CNR {>=}2) represented 25% of the contrast-enhancing (T1CE) regions and 10% of abnormal T2 regions outside T1CE (HyperT2). The presence of CNR2 was often an early indicator of the site of relapse after therapy. In fact, 75% of the voxels within the T1CE+CNR2 before therapy continued to exhibit CNR2 at relapse, compared with 22% of the voxels within the T1CE with normal CNR (p < 0.05). The location of new contrast enhancement with CNR2 corresponded in 80% of the initial HyperT2+CNR2 vs. 20.7% of the HyperT2 voxels with normal CNR (p < 0.05). Conclusion: Metabolically active regions represented a small percentage of pretreatment MRI abnormalities and were predictive for the site of post-RT relapse. The incorporation of MRSI data in the definition of RT target volumes for selective boosting may be a promising avenue leading to increased local control of glioblastomas.« less

Predictive value of minimal residual disease in Philadelphia-chromosome-positive acute lymphoblastic leukemia treated with imatinib in the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia, based on immunoglobulin/T-cell receptor and BCR/ABL1 methodologies

PubMed Central

Cazzaniga, Giovanni; De Lorenzo, Paola; Alten, Julia; Röttgers, Silja; Hancock, Jeremy; Saha, Vaskar; Castor, Anders; Madsen, Hans O.; Gandemer, Virginie; Cavé, Hélène; Leoni, Veronica; Köhler, Rolf; Ferrari, Giulia M.; Bleckmann, Kirsten; Pieters, Rob; van der Velden, Vincent; Stary, Jan; Zuna, Jan; Escherich, Gabriele; zur Stadt, Udo; Aricò, Maurizio; Conter, Valentino; Schrappe, Martin; Valsecchi, Maria Grazia; Biondi, Andrea

2018-01-01

The prognostic value of minimal residual disease (MRD) in Philadelphia-chromosome-positive (Ph+) childhood acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors is not fully established. We detected MRD by real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes (IG/TR) and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving Berlin-Frankfurt-Münster (BFM) high-risk (HR) therapy and post-induction intermittent imatinib (the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) study). MRD was monitored after induction (time point (TP)1), consolidation Phase IB (TP2), HR Blocks, reinductions, and at the end of therapy. MRD negativity progressively increased over time, both by IG/TR and BCR/ABL1. Of 90 patients with IG/TR MRD at TP1, nine were negative and none relapsed, while 11 with MRD<5×10−4 and 70 with MRD≥5×10−4 had a comparable 5-year cumulative incidence of relapse of 36.4 (15.4) and 35.2 (5.9), respectively. Patients who achieved MRD negativity at TP2 had a low relapse risk (5-yr cumulative incidence of relapse (CIR)=14.3[9.8]), whereas those who attained MRD negativity at a later date showed higher CIR, comparable to patients with positive MRD at any level. BCR/ABL1 MRD negative patients at TP1 had a relapse risk similar to those who were IG/TR MRD negative (1/8 relapses). The overall concordance between the two methods is 69%, with significantly higher positivity by BCR/ABL1. In conclusion, MRD monitoring by both methods may be functional not only for measuring response but also for guiding biological studies aimed at investigating causes for discrepancies, although from our data IG/TR MRD monitoring appears to be more reliable. Early MRD negativity is highly predictive of favorable outcome. The earlier MRD negativity is achieved, the better the prognosis. PMID:29079599

Predicting relapse risk in childhood acute lymphoblastic leukaemia.

PubMed

Teachey, David T; Hunger, Stephen P

2013-09-01

Intensive multi-agent chemotherapy regimens and the introduction of risk-stratified therapy have substantially improved cure rates for children with acute lymphoblastic leukaemia (ALL). Current risk allocation schemas are imperfect, as some children are classified as lower-risk and treated with less intensive therapy relapse, while others deemed higher-risk are probably over-treated. Most cooperative groups previously used morphological clearance of blasts in blood and marrow during the initial phases of chemotherapy as a primary factor for risk group allocation; however, this has largely been replaced by the detection of minimal residual disease (MRD). Other than age and white blood cell count (WBC) at presentation, many clinical variables previously used for risk group allocation are no longer prognostic, as MRD and the presence of sentinel genetic lesions are more reliable at predicting outcome. Currently, a number of sentinel genetic lesions are used by most cooperative groups for risk stratification; however, in the near future patients will probably be risk-stratified using genomic signatures and clustering algorithms, rather than individual genetic alterations. This review will describe the clinical, biological, and response-based features known to predict relapse risk in childhood ALL, including those currently used and those likely to be used in the near future to risk-stratify therapy. © 2013 John Wiley & Sons Ltd.

Neural Correlates of Graphic Cigarette Warning Labels Predict Smoking Cessation Relapse

PubMed Central

Owens, Max M.; MacKillop, James; Gray, Joshua C.; Hawkshead, Brittany E.; Murphy, Cara M.; Sweet, Lawrence H.

2017-01-01

Exposure to graphic warning labels (GWLs) on cigarette packaging has been found to produce heightened activity in brain regions central to emotional processing and higher-order cognitive processes. The current study extends this literature by using functional magnetic resonance imaging (fMRI) to investigate neural activation in response to GWLs and use it to predict relapse in an evidence-based smoking cessation treatment program. Participants were 48 treatment-seeking nicotine-dependent smokers who completed an fMRI paradigm in which they were exposed to GWLs, text-only warning labels (TOLs), and matched control stimuli. Subsequently, they enrolled in smoking cessation treatment and their smoking behavior was monitored. Activation in bilateral amygdala, right dorsolateral prefrontal cortex, right inferior frontal gyrus, left medial temporal gyrus, bilateral occipital lobe, and bilateral fusiform gyrus was greater during GWLs than TOLs. Neural response in the ventromedial prefrontal cortex (vmPFC) during exposure to GWLs (relative to a visual control image) predicted relapse during treatment beyond baseline demographic and dependence severity, but response in the amygdala to GWLs did not. These findings suggest that neurocognitive processes in the vmPFC may be critical to understanding how GWL’s induce behavior change and may be useful as a predictor of smoking cessation treatment prognosis. PMID:28236714

Centralization as a predictor of provocation discography results in chronic low back pain, and the influence of disability and distress on diagnostic power.

PubMed

Laslett, Mark; Oberg, Birgitta; Aprill, Charles N; McDonald, Barry

2005-01-01

The "centralization phenomenon" (CP) is the progressive retreat of referred pain towards the spinal midline in response to repeated movement testing (a McKenzie evaluation). A previous study suggested that it may have utility in the clinical diagnosis of discogenic pain and may assist patient selection for discography and specific treatments for disc pain. Estimation of the diagnostic predictive power of centralization and the influence of disability and patient distress on diagnostic performance, using provocation discography as a criterion standard for diagnosis, in chronic low back pain patients. This study was a prospective, blinded, concurrent, reference standard-related validity design carried out in a private radiology clinic specializing in diagnosis of chronic spinal pain. Consecutive patients with persistent low back pain were referred to the study clinic by orthopedists and other medical specialists for interventional radiological diagnostic procedures. Patients were typically disabled and displayed high levels of psychosocial distress. The sample included patients with previous lumbar surgery, and most had unsuccessful conservative therapies previously. results of provocation discography. The CP. Psychometric evaluation: Roland-Morris, Zung, Modified Somatic Perception questionnaires, Distress Risk Assessment Method, and 100-mm visual analog scales for pain intensity. Patients received a single physical therapy examination, followed by lumbar provocation discography. Sensitivity, specificity, and likelihood ratios of the CP were estimated in the group as a whole and in subgroups defined by psychometric measures. A total of 107 patients received the clinical examination and discography at two or more levels and post-discography computed tomography. Thirty-eight could not tolerate a full physical examination and were excluded from the main analysis. Disability and pain intensity ratings were high, and distress was common. Sensitivity, specificity, and positive likelihood ratios for centralization observed during repeated movement testing for pain distribution and intensity changes were 40%, 94%, and 6.9 respectively. In the presence of severe disability, sensitivity, specificity, and positive likelihood ratios were 46%, 80%, 3.2 and for distress, 45%, 89%, 4.1. In the subgroups with moderate, minimal, or no disability, sensitivity and specificity were 37%, 100% and for no or minimal distress 35%, 100%. Centralization is highly specific to positive discography but specificity is reduced in the presence of severe disability or psychosocial distress.

The Novaco Anger Scale--Provocation Inventory (1994 Version) in Dutch Forensic Psychiatric Patients

ERIC Educational Resources Information Center

Hornsveld, Ruud H. J.; Muris, Peter; Kraaimaat, Floris W.

2011-01-01

We examined the psychometric properties of the Novaco Anger Scale--Provocation Inventory (NAS-PI, 1994 version) in Dutch violent forensic psychiatric patients and secondary vocational students. A confirmatory factor analysis of the subscale structure of the NAS was carried out, reliability was investigated, and relations were calculated between…

Creating Crossroads for Self-Authorship: Investigating the Provocative Moment

ERIC Educational Resources Information Center

Pizzolato, Jane Elizabeth

2005-01-01

Through examination of 613 students' narratives about self-selected important decisions, I investigated the student and situation characteristics related to provocation and use of self authored ways of knowing. The findings gesture toward both particular skills students may need to develop in order to self-author, as well as suggest that movement…

Children's Moral Reasoning about Family and Peer Violence: The Role of Provocation and Retribution.

ERIC Educational Resources Information Center

Astor, Ron A.

1994-01-01

Examined violent and nonviolent inner-city children's moral reasoning about violence in family and peer situations. All of the children condemned unprovoked violence. With provoked situations, the violent group focused more on the immorality of the provocation and perceived force akin to reciprocal justice, whereas the nonviolent group perceived…

Provocative Pedagogies in e-Learning: Making the Invisible Visible

ERIC Educational Resources Information Center

Sinclair, Anne

2009-01-01

The purpose of this case study was to explore the experiences of participants (practicing teachers) involved in an online course entitled: "Reflective Practice for Teachers." Using a provocative pedagogy in the course, the teachers were challenged to confront beliefs and assumptions about teaching and learning and become active participants in the…

Making Choices: Simultaneous Report and Provocative Statements, Tools for Appreciative Inquiry

ERIC Educational Resources Information Center

Nelson, Eric M.; Wright, Christine M.

2011-01-01

Many educators find that students do not participate actively in class, and are constantly seeking a variety of techniques to encourage student participation. The focus of this paper is to show how simultaneous report and provocative statements can be combined to foster appreciative inquiry, thereby, creating a learning environment with greater…

Automatic avoidance tendencies for alcohol cues predict drinking after detoxification treatment in alcohol dependence.

PubMed

Field, Matt; Di Lemma, Lisa; Christiansen, Paul; Dickson, Joanne

2017-03-01

Alcohol dependence is characterized by conflict between approach and avoidance motivational orientations for alcohol that operate in automatic and controlled processes. This article describes the first study to investigate the predictive validity of these motivational orientations for relapse to drinking after discharge from alcohol detoxification treatment in alcohol-dependent patients. One hundred twenty alcohol-dependent patients who were nearing the end of inpatient detoxification treatment completed measures of self-reported (Approach and Avoidance of Alcohol Questionnaire; AAAQ) and automatic (modified Stimulus-Response Compatibility task) approach and avoidance motivational orientations for alcohol. Their drinking behavior was assessed via telephone follow-ups at 2, 4, and 6 months after discharge from treatment. Results indicated that, after controlling for the severity of alcohol dependence, strong automatic avoidance tendencies for alcohol cues were predictive of higher percentage of heavy drinking days (PHDD) at 4-month (β = 0.22, 95% CI [0.07, 0.43]) and 6-month (β = 0.22, 95% CI [0.01, 0.42]) follow-ups. We failed to replicate previous demonstrations of the predictive validity of approach subscales of the AAAQ for relapse to drinking, and there were no significant predictors of PHDD at 2-month follow-up. In conclusion, strong automatic avoidance tendencies predicted relapse to drinking after inpatient detoxification treatment, but automatic approach tendencies and self-reported approach and avoidance tendencies were not predictive in this study. Our results extend previous findings and help to resolve ambiguities with earlier studies that investigated the roles of automatic and controlled cognitive processes in recovery from alcohol dependence. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS.

PubMed

Tomassini, V; De Giglio, L; Reindl, M; Russo, P; Pestalozza, I; Pantano, P; Berger, T; Pozzilli, C

2007-11-01

The aim of this study was to test the contribution of anti-myelin antibodies in predicting conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) when considering either Poser's or McDonald's diagnostic criteria. Fifty-one patients with CIS and abnormal brain MRI were imaged monthly for six months and then at 12, 18, 24, 36 months. At baseline serum samples testing antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) and myelin basic protein (anti-MBP) were collected. During the 36-month follow-up, 26 (51%) patients developed a relapse thus becoming clinically definite MS (CDMS) according to Poser's criteria; 46 (90.2%) patients converted to MS according to McDonald's criteria. Out of 51 patients, 28 (54.9%) had either double or single positivity for anti-myelin antibodies. Antibody status significantly predicted MS according to Poser's criteria (P=0.004), but did not according to the McDonald's criteria. When compared to antibody negative patients, the risk of developing a relapse was 8.9 (95% CI: 2.7-29.8; P<0.001) for anti-MBP positive (anti-MBP+) patients and 1.5 (95% CI: 0.4-5.4; P=0.564) for those anti-MOG positive (anti-MOG+); double positive patients (ie, anti-MBP+/anti-MOG+) had a risk of relapse's occurrence equal to 3.4 (95% CI: 1.1-10.2; P=0.031). Also, the antibody status predicted the median time span from CIS to CDMS, that was of 36 months in the anti-MOG-/anti-MBP- group, 33 months in the anti-MOG+/anti-MBP- group, 24 months in the anti-MOG+/anti-MBP+ group and 12 months in the anti-MOG-/anti-MBP+ patients (P=0.003 by ANOVA). Our data support the prognostic value of anti-myelin antibodies in CIS patients at risk of CDMS, with positive patients showing shorter time interval to relapse occurrence than negative patients.

A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis.

PubMed

Arias, Maria Theresa; Vande Casteele, Niels; Vermeire, Séverine; de Buck van Overstraeten, Anthony; Billiet, Thomas; Baert, Filip; Wolthuis, Albert; Van Assche, Gert; Noman, Maja; Hoffman, Ilse; D'Hoore, Andre; Gils, Ann; Rutgeerts, Paul; Ferrante, Marc

2015-03-01

Infliximab is effective for patients with refractory ulcerative colitis (UC), but few factors have been identified that predict long-term outcome of therapy. We aimed to identify a panel of markers associated with outcome of infliximab therapy to help physicians make personalized treatment decisions. We collected data from the first 285 patients with refractory UC (41% female; median age, 39 y) treated with infliximab before July 2012 at University Hospitals Leuven, in Belgium. We performed a Cox regression analysis to identify independent factors that predicted relapse-free and colectomy-free survival, and used these factors to create a panel of markers (risk panel). During a median follow-up period of 5 years, 61% of patients relapsed and 20% required colectomy. Independent predictors of relapse-free survival included short-term complete clinical response (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.35-5.97; P < .001), mucosal healing (OR, 1.87; 95% CI, 1.17-2.98; P = .009), and absence of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) (OR, 1.96; 95% CI, 1.23-3.12; P = .005). Independent predictors of colectomy-free survival included short-term clinical response (OR, 7.74; 95% CI, 2.76-21.68; P < .001), mucosal healing (OR, 4.02; 95% CI, 1.16-13.97; P = .028), baseline level of C-reactive protein (CRP) of 5 mg/L or less (OR, 2.95; 95% CI, 1.26-6.89; P = .012), and baseline level of albumin of 35 g/L or greater (OR, 3.03; 95% CI, 1.12-8.22; P = .029). Based on serologic analysis of a subgroup of 112 patients, levels of infliximab greater than 2.5 μg/mL at week 14 of treatment predicted relapse-free survival (P < .001) and colectomy-free survival (P = .034). A risk panel that included levels of pANCA, CRP, albumin, clinical response, and mucosal healing identified patients at risk for UC relapse or colectomy (both P < .001). Clinical response and mucosal healing were confirmed as independent predictors of long-term outcome from infliximab therapy in patients with UC. We identified additional factors (levels of pANCA, CRP, and albumin) to create a risk panel that predicts long-term outcomes of therapy. Serum levels of infliximab at week 14 of treatment also were associated with patient outcomes. Our risk panel and short-term serum levels of infliximab therefore might be used to guide therapy. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Prognostic Prediction Model for Second Allogeneic Stem-Cell Transplantation in Patients With Relapsed Acute Myeloid Leukemia: Single-Center Report.

PubMed

Park, Sung-Soo; Kim, Hee-Je; Min, Kyoung Il; Min, Gi June; Jeon, Young-Woo; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung

2018-04-01

To identify factors affecting survival outcomes and to develop a prognostic model for second allogeneic stem-cell transplantation (allo-SCT2) for relapsed acute myeloid leukemia (AML) after the first autologous or allogeneic stem-cell transplantation. Seventy-eight consecutive adult AML patients who received allo-SCT2 were analyzed in this retrospective study. The 4-year overall survival (OS) rate was 28.7%. In multivariate analysis, poor cytogenetic risk at diagnosis, circulating blast ≥ 20% at relapse, duration from first transplantation to relapse < 9 months, and failure to achieve morphologic complete remission after allo-SCT2 were factors associated with poor OS. A prognostic model was developed with the following score system: intermediate and poor cytogenetic risk at diagnosis (0.5 and 1 point), peripheral blast ≥ 20% at relapse (1 point), duration from the first transplantation to relapse < 9 months (1 point), and failure to achieve morphologic complete remission after allo-SCT2 (1 point). The model identified 2 subgroups according to the 4-year OS rate: 51.3% in the low-risk group (score < 2) and 2.8% in the high-risk group (score ≥ 2) (P < .001). This prognostic model might be useful to make an appropriate decision for allo-SCT2 in relapsed AML after the first autologous or allogeneic stem-cell transplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

PubMed Central

Gross, V; Andus, T; Ecker, K; Raedler, A; Loeschke, K; Plauth, M; Rasenack, J; Weber, A; Gierend, M; Ewe, K; Scholmerich, J; Budesonide, S

1998-01-01

Background—The relapse rate after steroid induced remission in Crohn's disease is high. 
Aims—To test whether oral pH modified release budesonide (3 × 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. 
Methods—In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 × 1 mg budesonide (n=84) or placebo (n=95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. 
Results—Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. 
Conclusion—Oral pH modified release budesonide at a dose of 3 × 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease. 

 Keywords: budesonide; Crohn's disease; maintenance of remission PMID:9616309

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

PubMed

Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

2017-08-01

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

Predicting Time-to-Relapse in Breast Cancer Using Neural Networks

DTIC Science & Technology

1997-12-01

CODE 17. SECURITY CLASSIFICATION OF REPORT Unclassified 118. SECURITY CLASSIFICATION OF THIS PAGE Unclassified 19. SECURITY CLASSIFICATION OF...Lowell WE, and Davis GL. A neural network that predicts psychiatric length of stay. MD Computing 10:87-92, 1993. Ebell MH. Artificial neural netowrks

Predictive modeling of addiction lapses in a mobile health application.

PubMed

Chih, Ming-Yuan; Patton, Timothy; McTavish, Fiona M; Isham, Andrew J; Judkins-Fisher, Chris L; Atwood, Amy K; Gustafson, David H

2014-01-01

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-comprehensive health enhancement support system (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients' recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support. © 2013.

Predictive Modeling of Addiction Lapses in a Mobile Health Application

PubMed Central

Chih, Ming-Yuan; Patton, Timothy; McTavish, Fiona M.; Isham, Andrew; Judkins-Fisher, Chris L.; Atwood, Amy K.; Gustafson, David H.

2013-01-01

The chronically relapsing nature of alcoholism leads to substantial personal, family, and societal costs. Addiction-Comprehensive Health Enhancement Support System (A-CHESS) is a smartphone application that aims to reduce relapse. To offer targeted support to patients who are at risk of lapses within the coming week, a Bayesian network model to predict such events was constructed using responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol-dependent individuals who recently completed residential treatment. The Weekly Check-in is a self-monitoring service, provided in A-CHESS, to track patients’ recovery progress. The model showed good predictability, with the area under receiver operating characteristic curve of 0.829 in the 10-fold cross-validation and 0.912 in the external validation. The sensitivity/specificity table assists the tradeoff decisions necessary to apply the model in practice. This study moves us closer to the goal of providing lapse prediction so that patients might receive more targeted and timely support. PMID:24035143

Predicting the Initial Lapse Using a Mobile Health Application after Alcohol Detoxification

ERIC Educational Resources Information Center

Chih, Ming-Yuan

2013-01-01

The prediction and prevention of the initial lapse--which is defined as the first lapse after a period of abstinence--is important because the initial lapse often leads to subsequent lapses (within the same lapse episode) or relapse. The prediction of the initial lapse may allow preemptive intervention to be possible. This dissertation reports on…

Utility of the PET-CT in the evaluation of early response to treatment in the diffuse large B-cell lymphoma. Preliminary results.

PubMed

Cortés Romera, M; Gámez Cenzano, C; Caresia Aróztegui, A P; Martín-Comín, J; González-Barca, E; Ricart Brulles, Y; Palacios Abufón, A; Robles Barba, J; Rodríguez-Bel, L; Rossi Seoane, S; Fernández de Sevilla, A

2012-01-01

To assess the role of FDG-PET/CT performed after the first cycles of chemotherapy in the prediction of response to treatment in patients with diffuse large B-cell lymphoma. Twenty patients (mean age: 48 years) were included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3 times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response assessment), and 3) End of treatment (evaluation of final response). Early PET/CT findings were correlated to the end-treatment PET/CT and follow-up. The evaluation of the response was established according to the decrease in uptake of the lesions (SUVmax). In the early assessment, a good response indicator (GRI) was obtained when the lesion disappeared or had more than 50% reduction in SUVmax. At the end of the treatment, a complete metabolic response (CMR) was determined in negative PET scans. Follow-up was superior to 19 months and final outcome was established as progression/relapse or no evidence of disease (NED). At the early treatment evaluation, 16/16 patients of initial staging (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation, 14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were alive with NED in the follow-up while 1 relapsed. In the second group, 2/2 patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and another relapsed. FDG-PET/CT after the first cycles of chemotherapy is useful to monitor treatment due to its high negative predictive value (87.5%), using it to modify treatment early in the non-responders. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated Vasculitis

PubMed Central

Jones, Britta E.; Yang, Jiajin; Muthigi, Akhil; Hogan, Susan L.; Hu, Yichun; Starmer, Joshua; Henderson, Candace D.; Poulton, Caroline J.; Brant, Elizabeth J.; Pendergraft, William F.; Jennette, J. Charles; Falk, Ronald J.

2017-01-01

ANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase (MPO) and proteinase 3 (PRTN3) in leukocytes of patients with ANCA-associated vasculitis observed longitudinally (n=82) and of healthy controls (n=32). Patients with active disease demonstrated hypomethylation of MPO and PRTN3 and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, MPO and PRTN3 expression correlated with DNA methylation. Kaplan–Meier estimate of relapse revealed patients with increased DNA methylation at the PRTN3 promoter had a significantly greater probability of a relapse-free period (P<0.001), independent of ANCA serotype. Patients with decreased DNA methylation at the PRTN3 promoter had a greater risk of relapse (hazard ratio, 4.55; 95% confidence interval, 2.09 to 9.91). Thus, changes in the DNA methylation status of the PRTN3 promoter may predict the likelihood of stable remission and explain autoantigen gene regulation. PMID:27821628

[Clinical research on clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia].

PubMed

Yi, Zhi-gang; Cui, Lei; Gao, Chao; Jin, Mei; Zhang, Rui-dong; Li, Zhi-gang; Wu, Min-yuan

2011-03-01

To investigate the clinical value of clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia (BCP-ALL), and to assess the applicative value of different indexes. From April 2005 to April 2008, 206 children with de novo BCP-ALL were admitted. We firstly analyzed the effect of clearance of leukemic cells during induction of remission therapy on relapse-free survival (RFS). Four indexes were used to assess the clearance of leukemic cells including prednisone response on day 8 (d8-PR), percentage of lymphoblast in bone marrow on day 22 (d22-BM) and day 33 (d33-BM), and bone marrow (BM) minimal residual disease (MRD) detection on day 33 (d33-MRD). Then the sensitivity, specificity, positive predictive value and negative predictive value of the four indexes to assess their ability to predict relapse were analyzed. Finally, the consistency between two of the four indexes to explore the relationships among them were analyzed. There were significant differences between RFS of the sub-groups divided according to d8-PR, d22-BM, d33-BM, d33-MRD (P < 0.01); Cox proportional hazard model analysis showed that d33-MRD ≥ 10(-3) and positive BCR/ABL fusion gene were the independent prognostic factors. Sensitivity of d33-MRD was higher than that of morphology detection (d22-BM, d33-BM and d8-PR) in prediction of relapse, and positive predictive value of morphology detection was higher than that of d33-MRD. Sensitivity could be greatly increased by combination with clinical and biological characteristics. Consistency could not be found between d8-PR and d22-BM, d33-BM, d33-MRD, as well as between d22-BM, d33-BM, and d33-MRD. However, all cases of d22-BM, d33-BM M2/M3 were d33-MRD ≥ 10(-3), while the same phenomenon could not be found for patients with poor d8-PR. Clearance of leukemic cell during induction of remission therapy in children with BCP-ALL had important clinical value. Sensitivity of MRD detection after induction of remission therapy was higher than that of morphological analysis to predict relapse. Morphological analysis could only identify a few patients with very high risk of relapse and the sensitivity could be increased by combination with clinical biological characteristics. The simple prednisone response may contain some prognostic information that could not be covered by analysis of BM cells. It may be the best way to assess the clearance of leukemic cells to combine the prednisone response with MRD detection after induction of remission therapy.

Mother–Child Communication and Maternal Depressive Symptoms in Families of Children With Cancer: Integrating Macro and Micro Levels of Analysis

PubMed Central

Dunn, Madeleine J.; Zuckerman, Teddi; Hughart, Leighann; Vannatta, Kathryn; Gerhardt, Cynthia A.; Saylor, Megan; Schuele, C. Melanie; Compas, Bruce E.

2013-01-01

Objectives This study examines associations between maternal depressive symptoms and macro- and micro-level aspects of mothers’ communication about their children’s cancer. Methods Mothers reported depressive symptoms after diagnosis or relapse (child mean age = 10.4 years; 53% male). Mother–child dyads (N = 94) were subsequently observed discussing the child’s cancer and maternal communication was coded. Results Macro-level indicators (positive and negative communication) were associated with certain micro-level indicators of communication (topic maintenance, reflections, reframes, and imperatives). Higher depressive symptoms predicted lower positive communication and higher negative communication. Maternal reflections and imperatives predicted positive communication, and topic maintenance and reframes predicted negative communication, beyond child age, family income, and depressive symptoms. Conclusions Findings suggest concrete targets for improving communication in families after diagnosis or relapse. PMID:23616622

Individual Differences in Responses to Provocation and Frequent Victimization by Peers

ERIC Educational Resources Information Center

Champion, Kelly M.; Clay, Daniel L.

2007-01-01

This study examined associations between victimization by peers and intention to respond to provocative events as a function of anger arousal and motivation to improve the situation in a cross-sectional sample of school-age children (N = 506, 260 males, 246 females). Results demonstrated that more intense anger and more retaliatory motivation were…

Children's Emotion Regulation: Self-Report and Physiological Response to Peer Provocation

ERIC Educational Resources Information Center

Hessler, Danielle M.; Katz, Lynn Fainsilber

2007-01-01

The authors examined the notion that children's emotion regulation (ER) is a uniform skill by (a) investigating the concordance between self-report of ER and physiological measures and by (b) examining ER in a specific context (e.g., peer provocation) and context-free manner (e.g., during a semistructured interview of ER abilities). Seventy-two…

The Photomontages of John Heartfield: A Provocative Teaching Tool for "Landeskunde."

ERIC Educational Resources Information Center

Mathieu, Gustave Bording

1992-01-01

A case is made for the use of the politically provocative photomontages of Heartfield (a.k.a. Berlin-born Helmut Herzfeld) in the German classroom. The interplay of language, art, culture, and history makes them especially useful as realia. A model for teaching them is presented, including a chronology and nine reproductions. (Author/LB)

Manifestation of J wave induced by acetylcholine applied for a coronary spasm provocation test in a patient with aborted sudden cardiac death.

PubMed

Kodama, Hiroyuki; Fujita, Kazumasa; Moriyama, Shouhei; Irie, Kei; Noda, Hirotaka; Yokoyama, Taku; Fukata, Mitsuhiro; Arita, Takeshi; Odashiro, Keita; Maruyama, Toru; Akashi, Koichi

2017-06-01

A 51-year-old man with a resuscitation episode was referred to our hospital. Coronary angiography revealed a focal spasm overlapped with organic stenosis where a bare metal stent was implanted. Acetylcholine (ACh) provocation test did not induce chest pain. It revealed no discernible ST-T changes but unmasked a J wave at the end of the QRS complex, which was associated with short-coupled repetitive premature ventricular beats. A J wave reportedly appears immediately before the onset of ventricular fibrillation caused by vasospastic angina. However, a J wave observed newly after a coronary spasm provocation test using ACh without ST-T changes is informative when considering the mechanisms of the J wave.

A behavioral economic reward index predicts drinking resolutions: moderation revisited and compared with other outcomes.

PubMed

Tucker, Jalie A; Roth, David L; Vignolo, Mary J; Westfall, Andrew O

2009-04-01

Data were pooled from 3 studies of recently resolved community-dwelling problem drinkers to determine whether a behavioral economic index of the value of rewards available over different time horizons distinguished among moderation (n = 30), abstinent (n = 95), and unresolved (n = 77) outcomes. Moderation over 1- to 2-year prospective follow-up intervals was hypothesized to involve longer term behavior regulation processes than abstinence or relapse and to be predicted by more balanced preresolution monetary allocations between short-term and longer term objectives (i.e., drinking and saving for the future). Standardized odds ratios (ORs) based on changes in standard deviation units from a multinomial logistic regression indicated that increases on this "Alcohol-Savings Discretionary Expenditure" index predicted higher rates of abstinence (OR = 1.93, p = .004) and relapse (OR = 2.89, p < .0001) compared with moderation outcomes. The index had incremental utility in predicting moderation in complex models that included other established predictors. The study adds to evidence supporting a behavioral economic analysis of drinking resolutions and shows that a systematic analysis of preresolution spending patterns aids in predicting moderation.

Predictors of heroin relapse: Personality traits, impulsivity, COMT gene Val158met polymorphism in a 5-year prospective study in Shanghai, China.

PubMed

Su, Hang; Li, Zhibin; Du, Jiang; Jiang, Haifeng; Chen, Zhikang; Sun, Haiming; Zhao, Min

2015-12-01

Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse. © 2015 Wiley Periodicals, Inc.

Preoperative [18F]-fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes may aid in selecting patients with oral cavity squamous cell carcinoma for salvage therapy after relapse.

PubMed

Liao, Chun-Ta; Chang, Joseph Tung-Chieh; Wang, Hung-Ming; Ng, Shu-Hang; Huang, Shiang-Fu; Chen, I-How; Hsueh, Chuen; Lee, Li-Yu; Lin, Chih-Hung; Cheng, Ann-Joy; Yen, Tzu-Chen

2009-11-01

Relapse of tumours in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a dismal outcome. In this prospective study, we sought to investigate the clinical significance of the preoperative maximal standardized uptake value (SUVmax) at the neck lymph nodes in selecting patients with OSCC for salvage therapy after relapse. Between 2002 and 2007, 108 patients with early relapse of OSCC (n=75) or late relapse of OSCC (n=33) were identified. Salvage therapy was performed in 47 patients. All patients underwent 2-deoxy-2[(18)F]-fluoro-D: -glucose positron emission tomography during the 2 weeks before surgery and neck dissection. All patients were followed for 12 months or more after surgery or until death. The optimal cut-off value for the neck lymph node SUVmax (SUVnodal-max) was selected according to the 5-year disease-specific survival (DSS) rate. Independent risk factors were identified by Cox regression analysis. The mean follow-up for all patients was 20.3 months (41.1 months for surviving patients). In the early relapse group, several prognostic factors were identified in univariate and multivariate analyses, including a SUVnodal-max value of >or=4.2. A scoring system based on univariate analysis was formulated. Patients with a score of 0 had a better 5-year DSS than those with scores of 1 or higher (58% vs. 5%, p=0.0003). In patients with late relapse, a SUVnodal-max value of >or=4.2 had the highest prognostic value for predicting the 5-year DSS (45% vs. 0%, p=0.0005). Among patients with relapsed OSCC, the SUVnodal-max value may aid in selecting patients for salvage therapy.

Hostile attributional bias and aggressive behavior in global context.

PubMed

Dodge, Kenneth A; Malone, Patrick S; Lansford, Jennifer E; Sorbring, Emma; Skinner, Ann T; Tapanya, Sombat; Tirado, Liliana Maria Uribe; Zelli, Arnaldo; Alampay, Liane Peña; Al-Hassan, Suha M; Bacchini, Dario; Bombi, Anna Silvia; Bornstein, Marc H; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Oburu, Paul; Pastorelli, Concetta

2015-07-28

We tested a model that children's tendency to attribute hostile intent to others in response to provocation is a key psychological process that statistically accounts for individual differences in reactive aggressive behavior and that this mechanism contributes to global group differences in children's chronic aggressive behavior problems. Participants were 1,299 children (mean age at year 1 = 8.3 y; 51% girls) from 12 diverse ecological-context groups in nine countries worldwide, followed across 4 y. In year 3, each child was presented with each of 10 hypothetical vignettes depicting an ambiguous provocation toward the child and was asked to attribute the likely intent of the provocateur (coded as benign or hostile) and to predict his or her own behavioral response (coded as nonaggression or reactive aggression). Mothers and children independently rated the child's chronic aggressive behavior problems in years 2, 3, and 4. In every ecological group, in those situations in which a child attributed hostile intent to a peer, that child was more likely to report that he or she would respond with reactive aggression than in situations when that same child attributed benign intent. Across children, hostile attributional bias scores predicted higher mother- and child-rated chronic aggressive behavior problems, even controlling for prior aggression. Ecological group differences in the tendency for children to attribute hostile intent statistically accounted for a significant portion of group differences in chronic aggressive behavior problems. The findings suggest a psychological mechanism for group differences in aggressive behavior and point to potential interventions to reduce aggressive behavior.

Hostile attributional bias and aggressive behavior in global context

PubMed Central

Dodge, Kenneth A.; Malone, Patrick S.; Lansford, Jennifer E.; Sorbring, Emma; Skinner, Ann T.; Tapanya, Sombat; Tirado, Liliana Maria Uribe; Zelli, Arnaldo; Alampay, Liane Peña; Al-Hassan, Suha M.; Bacchini, Dario; Bombi, Anna Silvia; Bornstein, Marc H.; Chang, Lei; Deater-Deckard, Kirby; Di Giunta, Laura; Oburu, Paul; Pastorelli, Concetta

2015-01-01

We tested a model that children’s tendency to attribute hostile intent to others in response to provocation is a key psychological process that statistically accounts for individual differences in reactive aggressive behavior and that this mechanism contributes to global group differences in children’s chronic aggressive behavior problems. Participants were 1,299 children (mean age at year 1 = 8.3 y; 51% girls) from 12 diverse ecological-context groups in nine countries worldwide, followed across 4 y. In year 3, each child was presented with each of 10 hypothetical vignettes depicting an ambiguous provocation toward the child and was asked to attribute the likely intent of the provocateur (coded as benign or hostile) and to predict his or her own behavioral response (coded as nonaggression or reactive aggression). Mothers and children independently rated the child’s chronic aggressive behavior problems in years 2, 3, and 4. In every ecological group, in those situations in which a child attributed hostile intent to a peer, that child was more likely to report that he or she would respond with reactive aggression than in situations when that same child attributed benign intent. Across children, hostile attributional bias scores predicted higher mother- and child-rated chronic aggressive behavior problems, even controlling for prior aggression. Ecological group differences in the tendency for children to attribute hostile intent statistically accounted for a significant portion of group differences in chronic aggressive behavior problems. The findings suggest a psychological mechanism for group differences in aggressive behavior and point to potential interventions to reduce aggressive behavior. PMID:26170281

Risk-adapted, treosulfan-based therapy with auto- and allo-SCT for relapsed/refractory aggressive NHL: a prospective phase-II trial.

PubMed

Koenigsmann, M; Casper, J; Kahl, C; Basara, N; Sayer, H G; Behre, G; Theurich, S; Christopeit, M; Mohren, M; Reichle, A; Metzner, B; Ganser, A; Stadler, M; Uharek, L; Balleisen, L; Hinke, A; Hinke, R; Niederwieser, D

2014-03-01

Since the outcome of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) is highly variable, a risk-adapted treatment approach was evaluated. After two cycles of DHAP, patients received high-dose treosulfan/etoposide/carboplatinum (TEC) and autologous stem cell rescue. After TEC, low-risk patients with late relapse (>1 year after first CR who achieved CR after DHAP received no further treatment. Patients with late relapse who achieved CR or PR only after TEC underwent a second cycle of TEC. High-risk patients with early relapse/refractory disease received treosulfan/fludarabine followed by allogeneic transplantation. Rituximab was added in patients with B-cell lymphoma (86%). At entry, 36% of all 57 patients had refractory disease, 32% early and 32% late relapse. During DHAP treatment, progression occurred in 32% of patients. Of 33 patients who received TEC, 5 received second TEC and 15 allogeneic transplantation. Main toxicity after TEC was oral mucositis (CTC grades 3 and 4 in 50% and 13%, respectively). In total, 42% patients achieved CR. Median OS was 21.4 months for all patients and 32.6 for those who underwent allogeneic transplantation. International prognostic index (IPI) at study entry was highly discriminative at predicting OS (P<0.0001). Risk-adapted, treosulfan-based therapy with auto- and allo-SCT is feasible. Long-term survival is possible with allogeneic transplantation.

Adolescents' responses to online peer conflict: How self‐evaluation and ethnicity matter

PubMed Central

Bos, Marieke G.N.; Stevenson, Claire E.

2017-01-01

Abstract For parents, online platforms where their children interact with others often feel like a “black box” in terms of what exactly is happening. In this study, we developed an ecologically valid online computer game in which a (computer‐generated) peer teammate tried to provoke frustration, in order to examine (a) adolescents' responses and (b) how indices of self‐evaluation (i.e., sense of coherence and self‐esteem) and demographic variables (i.e., gender and ethnicity) matter to these responses. Like gender, being a member of a minority or majority group may influence how provocations by peers are interpreted, influencing how one responds. Fifteen‐year‐old Dutch and Moroccan‐Dutch adolescents (N = 167) completed self‐reports and played the online computer game. The game indeed elicited frustration, with increased self‐reported anger. Moreover, expressions of displeasure were much more common during and after provocation than before provocation. Crucially, perceived self‐evaluation mattered; higher levels of sense of coherence but lower levels of self‐esteem (only in Moroccan‐Dutch group) contributed to fewer expressions of displeasure. Gender did not play a moderating role. Our findings provide initial insights into individual differences in adolescents' responses in an online peer‐conflict situation. Highlights We studied Dutch and Moroccan-Dutch adolescents' responses during online peer provocation and how self-evaluation and demographic variables matter.Provocation by the (computer-generated) peer teammate increased expressions of displeasure.More sense of coherence but less self-esteem was associated with fewer expressions of displeasure, but ethnicity moderated the effect with self-esteem. PMID:29780286

Food hypersensitivity reactions in Soft Coated Wheaten Terriers with protein-losing enteropathy or protein-losing nephropathy or both: gastroscopic food sensitivity testing, dietary provocation, and fecal immunoglobulin E.

PubMed

Vaden, S L; Hammerberg, B; Davenport, D J; Orton, S M; Trogdon, M M; Melgarejo, L T; VanCamp, S D; Williams, D A

2000-01-01

The purpose of this study was to evaluate Soft Coated Wheaten Terriers (SCWTs) affected with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) or both for allergy to food. We performed gastroscopic food-sensitivity testing, a provocative dietary trial, and measurement of fecal immunoglobulin E (IgE) in 6 SCWTs affected with PLE or PLN or both. Positive gastroscopic food-sensitivity test reactions were noted in 5 of 6 dogs. Positive reactions were found to milk in 4 dogs, to lamb in 2 dogs, and to wheat and chicken each in 1 dog. Adverse reactions to food (diarrhea, vomiting, or pruritus) were detected in all 6 dogs during the provocative dietary trial. Adverse reactions were found to corn in 5 dogs, to tofu in 3 dogs, to cottage cheese in 2 dogs, to milk in 2 dogs, to farina cream of wheat in 2 dogs, and to lamb in 2 dogs. Serum albumin concentrations significantly decreased and fecal alpha1-protease inhibitor concentration significantly increased 4 days after the provocative trial when compared with baseline values. Antigen-specific fecal IgE varied throughout the provocative trial, with peak levels following ingestion of test meals. We conclude that food hypersensitivities are present in SCWTs affected with the syndrome of PLE/PLN. Mild inflammatory bowel disease was already established in the 6 SCWTs of this report at the time of study, making it impossible to determine if food allergies were the cause or result of the enteric disease.

Adolescents' responses to online peer conflict: How self-evaluation and ethnicity matter.

PubMed

Novin, Sheida; Bos, Marieke G N; Stevenson, Claire E; Rieffe, Carolien

2018-01-01

For parents, online platforms where their children interact with others often feel like a "black box" in terms of what exactly is happening. In this study, we developed an ecologically valid online computer game in which a (computer-generated) peer teammate tried to provoke frustration, in order to examine (a) adolescents' responses and (b) how indices of self-evaluation (i.e., sense of coherence and self-esteem) and demographic variables (i.e., gender and ethnicity) matter to these responses. Like gender, being a member of a minority or majority group may influence how provocations by peers are interpreted, influencing how one responds. Fifteen-year-old Dutch and Moroccan-Dutch adolescents (N = 167) completed self-reports and played the online computer game. The game indeed elicited frustration, with increased self-reported anger. Moreover, expressions of displeasure were much more common during and after provocation than before provocation. Crucially, perceived self-evaluation mattered; higher levels of sense of coherence but lower levels of self-esteem (only in Moroccan-Dutch group) contributed to fewer expressions of displeasure. Gender did not play a moderating role. Our findings provide initial insights into individual differences in adolescents' responses in an online peer-conflict situation. We studied Dutch and Moroccan-Dutch adolescents' responses during online peer provocation and how self-evaluation and demographic variables matter.Provocation by the (computer-generated) peer teammate increased expressions of displeasure.More sense of coherence but less self-esteem was associated with fewer expressions of displeasure, but ethnicity moderated the effect with self-esteem.

Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation.

PubMed

Fakhouri, Fadi; Fila, Marc; Provôt, François; Delmas, Yahsou; Barbet, Christelle; Châtelet, Valérie; Rafat, Cédric; Cailliez, Mathilde; Hogan, Julien; Servais, Aude; Karras, Alexandre; Makdassi, Raifah; Louillet, Feriell; Coindre, Jean-Philippe; Rondeau, Eric; Loirat, Chantal; Frémeaux-Bacchi, Véronique

2017-01-06

The complement inhibitor eculizumab has dramatically improved the outcome of atypical hemolytic uremic syndrome. However, the optimal duration of eculizumab treatment in atypical hemolytic uremic syndrome remains debated. We report on the French atypical hemolytic uremic syndrome working group's first 2-year experience with eculizumab discontinuation in patients with atypical hemolytic uremic syndrome. Using the French atypical hemolytic uremic syndrome registry database, we retrospectively identified all dialysis-free patients with atypical hemolytic uremic syndrome who discontinued eculizumab between 2010 and 2014 and reviewed their relevant clinical and biologic data. The decision to discontinue eculizumab was made by the clinician in charge of the patient. All patients were closely monitored by regular urine dipsticks and blood tests. Eculizumab was rapidly (24-48 hours) restarted in case of relapse. Among 108 patients treated with eculizumab, 38 patients (nine children and 29 adults) discontinued eculizumab (median treatment duration of 17.5 months). Twenty-one patients (55%) carried novel or rare complement genes variants. Renal recovery under eculizumab was equally good in patients with and those without complement gene variants detected. After a median follow-up of 22 months, 12 patients (31%) experienced atypical hemolytic uremic syndrome relapse. Eight of 11 patients (72%) with complement factor H variants, four of eight patients (50%) with membrane cofactor protein variants, and zero of 16 patients with no rare variant detected relapsed. In relapsing patients, early reintroduction (≤48 hours) of eculizumab led to rapid (<7 days) hematologic remission and a return of serum creatinine to baseline level in a median time of 26 days. At last follow-up, renal function remained unchanged in nonrelapsing and relapsing patients compared with baseline values before eculizumab discontinuation. Pathogenic variants in complement genes were associated with higher risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Prospective studies are needed to identify biomarkers predictive of relapse and determine the best strategy of retreatment in relapsing patients. Copyright © 2016 by the American Society of Nephrology.

Seeing the World through Mortal Kombat-Colored Glasses: Violent Video Games and the Development of a Short-Term Hostile Attribution Bias.

ERIC Educational Resources Information Center

Kirsh, Steven J.

1998-01-01

Investigated the effects of playing violent versus non-violent video games on the interpretation of ambiguous provocation situation. Found that children playing a violent video game responded more negatively to three of six ambiguous provocation story questions than children playing the non-violent video game. Data suggest that playing violent…

Brain responses to symptom provocation and trauma-related short-term memory recall in coal mining accident survivors with acute severe PTSD.

PubMed

Hou, Cailan; Liu, Jun; Wang, Kun; Li, Lingjiang; Liang, Meng; He, Zhong; Liu, Yong; Zhang, Yan; Li, Weihui; Jiang, Tianzi

2007-05-04

Functional neuroimaging studies have largely been performed in patients with longstanding chronic posttraumatic stress disorder (PTSD). Additionally, memory function of PTSD patients has been proved to be impaired. We sought to characterize the brain responses of patients with acute PTSD and implemented a trauma-related short-term memory recall paradigm. Individuals with acute severe PTSD (n=10) resulting from a mining accident and 7 men exposed to the mining accident without PTSD underwent functional magnetic resonance imaging (fMRI) while performing the symptom provocation and trauma-related short-term memory recall paradigms. During symptom provocation paradigm, PTSD subjects showed diminished responses in right anterior cingulate gyrus, left inferior frontal gyrus and bilateral middle frontal gyrus and enhanced left parahippocampal gyrus response compared with controls. During the short-term memory recall paradigm, PTSD group showed diminished responses in right inferior frontal gyrus, right middle frontal and left middle occipital gyrus in comparison with controls. PTSD group exhibited diminished right parahippocampal gyrus response during the memory recall task as compared to the symptom provocation task. Our findings suggest that neurophysiological alterations and memory performance deficit have developed in acute severe PTSD.

Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

PubMed

Mamez, A C; Lévy, V; Chevallier, P; Blaise, D; Vigouroux, S; Xhaard, A; Fegueux, N; Contentin, N; Beguin, Y; Ifrah, N; Bulabois, C E; Suarez, F; Yakoub-Agha, I; Turlure, P; Deconink, E; Lamy, T; Cahn, J Y; Huynh, A; Maury, S; Fornecker, L M; Ouzegdouh, M; Bay, J O; Guillerm, G; Maillard, N; Michallet, M; Malfuson, J V; Bourhis, J H; Rialland, F; Oumedaly, R; Jubert, C; Leblond, V; Boubaya, M; Mohty, M; Nguyen, S

2016-03-01

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

PubMed

Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-07-02

Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

Reactivity to negative affect in smokers: the role of implicit associations and distress tolerance in smoking cessation.

PubMed

Cameron, Amy; Reed, Kathleen Palm; Ninnemann, Andrew

2013-12-01

Avoidance of negative affect is one motivational factor that explains smoking cessation relapse during cessation attempts. This negative reinforcement model of smoking cessation and relapse has demonstrated the importance of one's ability to tolerate nicotine withdrawal symptoms, particularly negative affect states, in remaining abstinent from smoking. Distress tolerance and implicit associations are two individual constructs that may influence the strength of this relationship. In this pilot study the authors examined implicit associations related to avoidance and negative affect using a modified Implicit Association Test (IAT), a measure designed to examine implicit associations related to negative affect and avoidance, and the relationship of these associations to distress tolerance and smoking relapse. In total, 40 participants were recruited through community flyers as part of a larger smoking cessation study. Participants completed a brief smoking history, behavioral distress tolerance assessments, and the modified IAT. Smoking status was assessed via phone 3days and 6days post-quit date. Results from a Cox proportional hazard model revealed that implicit associations between avoidance and negative affect were significantly negatively correlated with time to relapse after a smoking cessation attempt, whereas the behavioral distress tolerance assessments did not predict time to relapse. This study provides novel information about the cognitive associations that may underlie avoidant behavior in smokers, and may be important for understanding smoking relapse when negative affect states are particularly difficult to tolerate. Authors discuss the importance of implicit associations in understanding smoking relapse and how they can be targeted in treatment. © 2013.

Predictors of 12-Months Relapse After Withdrawal Treatment in Hospitalized Patients With Chronic Migraine Associated With Medication Overuse: A Longitudinal Observational Study.

PubMed

Raggi, Alberto; Giovannetti, Ambra M; Leonardi, Matilde; Sansone, Emanuela; Schiavolin, Silvia; Curone, Marcella; Grazzi, Licia; Usai, Susanna; D'Amico, Domenico

2017-01-01

Studies addressing relapse rates conflate relapse into chronic migraine (CM) and medication overuse (MO), and the consequent need to repeat withdrawal. We aim to identify 12-months predictors of relapse into CM (based on headaches frequency) separately from occurrence of another structured withdrawal. Hospitalized patients with CM-MO under withdrawal were enrolled. Candidate predictors included demographic, disability, quality of life, depression scores, general self-efficacy, social support, headaches frequency and intensity, class of overused medications, history of withdrawal treatment in the three years prior to enrollment, attendance to emergency room (ER) between enrollment and follow-up, nonattendance to outpatient neurological examinations. Logistic regressions was used to address the significant predictors for the two outcomes. Complete data were available for 177 patients: 60 (33.9%) relapsed into CM, 38 (21.5%) underwent another withdrawal treatment. Recent history of withdrawal treatments, ER admission after discharge and high baseline BDI-II scores were significant predictors in both models. In addition to this, high baseline headache frequency predicted relapse into another withdrawal treatment. Predictors or relapse into CM and of occurrence of another withdrawal by 12-months are somehow similar. It is important to assess presence of recent previous withdrawal treatments and to plan regular follow-up afterwards, in particular for patients with high headache frequency and relevant mood disturbances: in this way, it will be more likely that situations requiring further structured withdrawal treatments can be identified before patients have to refer to ER. © 2016 American Headache Society.

Correlates of motivation to change in pathological gamblers completing cognitive-behavioral group therapy.

PubMed

Gómez-Peña, Mónica; Penelo, Eva; Granero, Roser; Fernández-Aranda, Fernando; Alvarez-Moya, Eva; Santamaría, Juan José; Moragas, Laura; Neus Aymamí, Maria; Gunnard, Katarina; Menchón, José M; Jimenez-Murcia, Susana

2012-07-01

The present study analyzes the association between the motivation to change and the cognitive-behavioral group intervention, in terms of dropouts and relapses, in a sample of male pathological gamblers. The specific objectives were as follows: (a) to estimate the predictive value of baseline University of Rhode Island Change Assessment scale (URICA) scores (i.e., at the start of the study) as regards the risk of relapse and dropout during treatment and (b) to assess the incremental predictive ability of URICA scores, as regards the mean change produced in the clinical status of patients between the start and finish of treatment. The relationship between the URICA and the response to treatment was analyzed by means of a pre-post design applied to a sample of 191 patients who were consecutively receiving cognitive-behavioral group therapy. The statistical analysis included logistic regression models and hierarchical multiple linear regression models. The discriminative ability of the models including the four URICA scores regarding the likelihood of relapse and dropout was acceptable (area under the receiver operating haracteristic curve: .73 and .71, respectively). No significant predictive ability was found as regards the differences between baseline and posttreatment scores (changes in R(2) below 5% in the multiple regression models). The availability of useful measures of motivation to change would enable treatment outcomes to be optimized through the application of specific therapeutic interventions. © 2012 Wiley Periodicals, Inc.

Evaluation of expressed emotion in schizophrenia: a comparison of Caucasians and Mexican-Americans.

PubMed

Kopelowicz, Alex; Zarate, Roberto; Gonzalez, Veronica; Lopez, Steven R; Ortega, Paula; Obregon, Nora; Mintz, Jim

2002-05-01

Social desirability, while a recognized source of respondent bias among Mexican-Americans, has not been evaluated as an explanation for the lower rate of high expressed emotion (EE) found in the family members of Mexican-Americans versus Caucasians with schizophrenia. In this study, we tested the hypothesis that the lower rate of high EE (hostility and criticism) among Mexican-Americans was the result of cultural factors impacting on how information was reported by the Mexican-American relative of a patient with schizophrenia. We compared the ratings of EE between Caucasian (N = 17) and Mexican-American (N = 44) patients with schizophrenia or schizoaffective disorder and their key relatives using the level of expressed emotion (LEE) scale (paper and pencil instrument rated by the patient and relative separately) and the Five Minute Speech Sample (observational experimenter rated). The ability of the various measures to predict relapse over two years was also examined. Contrary to our hypothesis, there were no differences between patient and family measures within ethnic group. Mexican-American patients and relatives reported lower rates of high EE than Caucasians across all measures. High EE predicted relapse across measures for Caucasian participants, but did not predict relapse for Mexican-Americans on any of the measurement instruments. We discuss the implications of these findings on cross-cultural research and family interventions for individuals with psychotic disorders.

Optimal use of novel agents in chronic lymphocytic leukemia.

PubMed

Smith, Mitchell R; Weiss, Robert F

2018-05-07

Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse. The outcomes differ depending on the underlying clonal architecture, raising the concept that personalized approaches based on clinical evaluation of each patient's clonal architecture might optimize outcomes while minimizing toxicity and cost. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assaultive behavior. Does provocation begin in the front office?

PubMed

Blair, D T

1991-05-01

1. Provocation is an important risk predictor because these issues can be recognized, assessed, and appropriate interventions can be implemented to reduce the associated risks. It is only by the reduction of such "non-fixed" risk factors that any reduction of assaults can be accomplished. 2. Involuntary admission, patients with dementia or organic brain disorder, physical or verbal limits, staff attitude, denial of the possibility of assaults, and the educational level and clinical experience of the staff may help provoke an assaultive episode. 3. An important step is assessing the assault to identify provocation due to certain medical causes, and to document the extent of degeneration in patients with dementia or organic brain disorder. Medical intervention would be indicated and would appropriately address the causes of some violent episodes.

Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.

PubMed

Teter, Barbara; Agashivala, Neetu; Kavak, Katelyn; Chouhfeh, Lynn; Hashmonay, Ron; Weinstock-Guttman, Bianca

2014-06-01

Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. This retrospective study analyzed patients with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p = 0.009). Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation. © The Author(s) 2013.

A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.

PubMed

Sho, Shonan; Court, Colin M; Winograd, Paul; Russell, Marcia M; Tomlinson, James S

2017-12-01

Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Whole-exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse-free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap-validation was used to examine internal/external validity. We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%). In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54). Our proposed mutation panel identifies CRC patients at high-risk for recurrence, which may help guide adjuvant therapy and post-operative surveillance protocols. © 2017 Wiley Periodicals, Inc.

Changes in Religious Coping and Relapse to Drug Use Among Opioid-Dependent Patients Following Inpatient Detoxification

PubMed Central

Skalski, Linda M.; Meade, Christina S.

2013-01-01

Relapse rates remain high among people with opioid dependence. Identifying psychosocial factors associated with outcomes is important for informing behavioral treatments. This study examined religious coping, opioid use, and 12-step participation among 45 participants receiving inpatient opioid detoxification at baseline and follow-up. At baseline, higher positive coping was related to less frequent opioid use pre-admission (β = −.44, p < .001) and history of 12-step participation (OR = 2.33, p < .05). Decreases in negative coping after discharge predicted less opioid use (β = .55, p < .001), and increases in positive coping predicted more frequent 12-step program participation (β = .42, p < .05). Positive religious coping may be protective, while negative religious coping may be a barrier to treatment. PMID:21125425

Decreased dopamine activity predicts relapse in methamphetamine abusers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang G. J.; Wang, G.-J.; Smith, L.

2011-01-20

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested withinmore » 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.« less

Decreased dopamine activity predicts relapse in methamphetamine abusers.

PubMed

Wang, G J; Smith, L; Volkow, N D; Telang, F; Logan, J; Tomasi, D; Wong, C T; Hoffman, W; Jayne, M; Alia-Klein, N; Thanos, P; Fowler, J S

2012-09-01

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

Social knowledge in children with language impairments: examination of strategies, predicted consequences, and goals in peer conflict situations.

PubMed

Timler, Geralyn R

2008-09-01

This study investigated social knowledge in school-age children, aged 8-12 years, with and without language impairment (LI and TD groups). A hypothetical peer conflict task was administered to examine the relationship among prosocial responses and parent/teacher ratings of children's social behaviours. Stimuli included 12 hypothetical peer conflict vignettes presented in an open-ended and forced choice condition. The LI group generated (open-ended) and selected (forced choice) fewer prosocial strategies. When asked to predict a friend's reaction to a selected conflict resolution strategy, the LI group predicted fewer positive consequences; however, the proportion of prosocial strategies followed by prediction of a positive peer consequence was similar across groups. Both groups identified more self-interest than relationship goals as the rationale for selected strategies. In the LI group, teacher ratings of children's social skills and problems in peer provocation situations were associated with selection of prosocial strategies. Implications for clinical service providers are discussed.

A theoretical physicist's journey into biology: from quarks and strings to cells and whales.

PubMed

West, Geoffrey B

2014-10-08

Biology will almost certainly be the predominant science of the twenty-first century but, for it to become successfully so, it will need to embrace some of the quantitative, analytic, predictive culture that has made physics so successful. This includes the search for underlying principles, systemic thinking at all scales, the development of coarse-grained models, and closer ongoing collaboration between theorists and experimentalists. This article presents a personal, slightly provocative, perspective of a theoretical physicist working in close collaboration with biologists at the interface between the physical and biological sciences.

Fluorescence lifetime spectroscopy: potential for in-vivo estimation of skin fluorophores changes after low power laser treatment

NASA Astrophysics Data System (ADS)

Ferulova, Inesa; Lihachev, Alexey; Spigulis, Janis

2013-11-01

The impact of visible cwlaser irradiation on skin autofluorescence lifetimes was investigated in spectral range from 450 nm to 600 nm. Skin optical provocations were performed during 1 min by 405 nm low power cw laser with power density up to 20 mW/cm2. Autofluorescence lifetimes were measured before and immediately after the optical provocation.

The Relation between Early Adolescents' Trust Beliefs in Peers and Reactions to Peer Provocation: Attributions of Intention and Retaliation

ERIC Educational Resources Information Center

Rotenberg, Ken J.; Betts, Lucy R.; Moore, Jolene

2013-01-01

The authors examined the relation between early adolescents' trust beliefs in peers and both their attributions for, and retaliatory aggression to, peer provocation. One hundred and eight-five early adolescents (102 male) from the United Kingdom (M age = 12 years, 2 months, SD = 3 months) completed the Children's Generalized Trust Beliefs in peer…

Living Large: Affect Amplification in Visual Perception Predicts Emotional Reactivity to Events in Daily Life

PubMed Central

Palder, Spencer L.; Ode, Scott; Liu, Tianwei; Robinson, Michael D.

2012-01-01

It was hypothesized that affect-amplifying individuals would be more reactive to affective events in daily life. Affect amplification was quantified in terms of overestimating the font size of positive and negative, relative to neutral, words in a basic perception task. Subsequently, the same (N = 70) individuals completed a daily diary protocol in which they reported on levels of daily stressors, provocations, and social support as well as six emotion-related outcomes for 14 consecutive days. Individual differences in affect amplification moderated reactivity to daily affective events in all such analyses. For example, daily stressor levels predicted cognitive failures at high, but not low, levels of affect amplification. Affect amplification, then, appears to have widespread utility in understanding individual differences in emotional reactivity. PMID:22989107

Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal Cortex Activation to Negative Emotional Stimuli and General Risk-Taking

PubMed Central

Cyders, Melissa A.; Dzemidzic, Mario; Eiler, William J.; Coskunpinar, Ayca; Karyadi, Kenny A.; Kareken, David A.

2015-01-01

The tendency toward impulsive behavior under emotional duress (negative and positive urgency) predicts a wide range of maladaptive risk-taking and behavioral disorders. However, it remains unclear how urgency relates to limbic system activity as induced from emotional provocation. This study used functional magnetic resonance imaging to examine the relationship between brain responses to visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos) images during 6 fMRI scans. Brain activation was extracted from a priori limbic regions previously identified in studies of emotional provocation. The right posterior orbitofrontal cortex (OFC) and left amygdala were activated in the [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu] contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P = 0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative urgency also mediated the relationship between [Neg>Neu] activation and general risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left amygdala). Emotional cue-induced activation in right lateral OFC and left amygdala might relate to emotion-based risk-taking through negative urgency. PMID:24904065

[Latest advances in chronic pancreatitis].

PubMed

Domínguez-Muñoz, J Enrique

2014-09-01

This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma. | Office of Cancer Genomics

Cancer.gov

Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who have a poor response to chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients. In this study, we examined whether circulating miRNAs can be used as biomarkers in osteosarcoma patients.

Optimization of the intravenous glucose tolerance test in T2DM patients using optimal experimental design.

PubMed

Silber, Hanna E; Nyberg, Joakim; Hooker, Andrew C; Karlsson, Mats O

2009-06-01

Intravenous glucose tolerance test (IVGTT) provocations are informative, but complex and laborious, for studying the glucose-insulin system. The objective of this study was to evaluate, through optimal design methodology, the possibilities of more informative and/or less laborious study design of the insulin modified IVGTT in type 2 diabetic patients. A previously developed model for glucose and insulin regulation was implemented in the optimal design software PopED 2.0. The following aspects of the study design of the insulin modified IVGTT were evaluated; (1) glucose dose, (2) insulin infusion, (3) combination of (1) and (2), (4) sampling times, (5) exclusion of labeled glucose. Constraints were incorporated to avoid prolonged hyper- and/or hypoglycemia and a reduced design was used to decrease run times. Design efficiency was calculated as a measure of the improvement with an optimal design compared to the basic design. The results showed that the design of the insulin modified IVGTT could be substantially improved by the use of an optimized design compared to the standard design and that it was possible to use a reduced number of samples. Optimization of sample times gave the largest improvement followed by insulin dose. The results further showed that it was possible to reduce the total sample time with only a minor loss in efficiency. Simulations confirmed the predictions from PopED. The predicted uncertainty of parameter estimates (CV) was low in all tested cases, despite the reduction in the number of samples/subject. The best design had a predicted average CV of parameter estimates of 19.5%. We conclude that improvement can be made to the design of the insulin modified IVGTT and that the most important design factor was the placement of sample times followed by the use of an optimal insulin dose. This paper illustrates how complex provocation experiments can be improved by sequential modeling and optimal design.

Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients.

PubMed

Wesołowska-Andersen, A; Borst, L; Dalgaard, M D; Yadav, R; Rasmussen, K K; Wehner, P S; Rasmussen, M; Ørntoft, T F; Nordentoft, I; Koehler, R; Bartram, C R; Schrappe, M; Sicheritz-Ponten, T; Gautier, L; Marquart, H; Madsen, H O; Brunak, S; Stanulla, M; Gupta, R; Schmiegelow, K

2015-02-01

Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10-15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin-Frankfurt-Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6-6.3%) for the best group (72% of patients) to 76% (95% CI: 41-90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation.

Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

PubMed

Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

2018-05-01

The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

The interplay of history of depression and craving in terms of smoking relapse among treatment seeking smokers.

PubMed

Rodríguez-Cano, Rubén; Paulus, Daniel J; López-Durán, Ana; Martínez-Vispo, Carmela; Fernández Del Río, Elena; Becoña, Elisardo; Zvolensky, Michael J

2017-01-01

Although there is an interconnection between history of major depressive disorder and smoking, there has been relatively limited scientific attention oriented on the interplay between history of major depressive disorder and smoking maintenance processes. The current study sought to address whether history of major depressive disorder and post-cessation craving interact in the prediction of relapse among treatment-seeking smokers. Separate models were evaluated as a function of sex. Participants (n = 319, Mage = 41.7, 62.1% female) were treatment-seeking smokers who were abstinent at the end of six weekly 1-hour sessions involving psychosocial treatment for cessation. Participants completed a baseline assessment and reported post-cessation craving. Smoking status was assessed at 1-, 2-, 3-, 6-, and 12-month follow-up after the end of treatment. There was a significant interactive effect evident for females (B = 0.05, OR = 1.05, p = 0.013), but not males. The form of the interaction indicated females with history of major depressive disorder and greater post-treatment craving evinced the highest rate of relapse. Findings suggest that history of major depressive disorder and post-treatment craving are related to increased risk of relapse for female, but not male, smokers. Sex differences play a fundamental role in the explanation of the interaction of history of major depressive disorder and craving post-treatment in smoking relapse. Considering sex differences related to smoking relapse may help to tailor smoking cessation treatments.

Individual differences in responses to provocation and frequent victimization by peers.

PubMed

Champion, Kelly M; Clay, Daniel L

2007-02-01

This study examined associations between victimization by peers and intention to respond to provocative events as a function of anger arousal and motivation to improve the situation in a cross-sectional sample of school-age children (N = 506, 260 males, 246 females). Results demonstrated that more intense anger and more retaliatory motivation were positively associated with intentions to aggress and with frequency of victimization. The association between aggressive intentions to respond to anger provocation and victimization could be accounted for by subjective feelings of anger and motivation to retaliate. The contribution of emotion processes was stronger for boys than for girls. A post hoc examination of non-bullying participants revealed that motivation accounted for aggressive intentions among the non-bullies. Results support including anger management programs in prevention efforts that target the school climate and victims' risk for psychopathology.

Provocation testing to assist craniomandibular pain diagnosis.

PubMed

DuPont, John S; Brown, Christopher E

2010-04-01

Patients with TMD often present with complex pain symptoms, which can make it difficult to reach a diagnosis. Usually palpation of the masticatory muscles and TM joints, range of motion testing and imaging are used in the diagnostic process. Sometimes it is necessary to evaluate the jaw moving muscles from a functional prospective because they cannot be palpated due to inaccessibility or because they have other structures that are more superficial to them. In these instances, provocation testing can be a helpful adjunct in providing some insight into what is occurring in the area being tested and localizing a suspected source of pain. Anesthesia blocking can be used to confirm any positive findings. This article explores several provocation tests that can be used to evaluate conditions of the masticatory musculature, the TM joints and the stylomandibular ligament.

A Behavioral Economic Reward Index Predicts Drinking Resolutions: Moderation Re-visited and Compared with Other Outcomes

PubMed Central

Tucker, Jalie A.; Roth, David L.; Vignolo, Mary J.; Westfall, Andrew O.

2014-01-01

Data were pooled from three studies of recently resolved community-dwelling problem drinkers to determine whether a behavioral economic index of the value of rewards available over different time horizons distinguished among moderation (n = 30), abstinent (n = 95), and unresolved (n = 77) outcomes. Moderation over 1-2 year prospective follow-up intervals was hypothesized to involve longer term behavior regulation processes compared to abstinence or relapse and to be predicted by more balanced pre-resolution monetary allocations between short- and longer-term objectives (i.e., drinking and saving for the future). Standardized odds ratios (OR) based on changes in standard deviation units from a multinomial logistic regression indicated that increases on this “Alcohol-Savings Discretionary Expenditure” index predicted higher rates of both abstinence (OR = 1.93, p = .004) and relapse (OR = 2.89, p < .0001) compared to moderation outcomes. The index had incremental utility in predicting moderation in complex models that included other established predictors. The study adds to evidence supporting a behavioral economic analysis of drinking resolutions and shows that a systematic analysis of pre-resolution spending patterns aids in predicting moderation. PMID:19309182

Implicit but not explicit self-esteem predicts future depressive symptomatology.

PubMed

Franck, Erik; De Raedt, Rudi; De Houwer, Jan

2007-10-01

To date, research on the predictive validity of implicit self-esteem for depressive relapse is very sparse. In the present study, we assessed implicit self-esteem using the Name Letter Preference Task and explicit self-esteem using the Rosenberg self-esteem scale in a group of currently depressed patients, formerly depressed individuals, and never depressed controls. In addition, we examined the predictive validity of explicit, implicit, and the interaction of explicit and implicit self-esteem in predicting future symptoms of depression in formerly depressed individuals and never depressed controls. The results showed that currently depressed individuals reported a lower explicit self-esteem as compared to formerly depressed individuals and never depressed controls. In line with previous research, all groups showed a positive implicit self-esteem not different from each other. Furthermore, after controlling for initial depressive symptomatology, implicit but not explicit self-esteem significantly predicted depressive symptoms at six months follow-up. Although implicit self-esteem assessed with the Name Letter Preference Test was not different between formerly depressed individuals and never depressed controls, the findings suggest it is an interesting variable in the study of vulnerability for depression relapse.

When Habits Are Dangerous: Alcohol Expectancies and Habitual Decision Making Predict Relapse in Alcohol Dependence.

PubMed

Sebold, Miriam; Nebe, Stephan; Garbusow, Maria; Guggenmos, Matthias; Schad, Daniel J; Beck, Anne; Kuitunen-Paul, Soeren; Sommer, Christian; Frank, Robin; Neu, Peter; Zimmermann, Ulrich S; Rapp, Michael A; Smolka, Michael N; Huys, Quentin J M; Schlagenhauf, Florian; Heinz, Andreas

2017-12-01

Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. Ninety detoxified, medication-free, alcohol-dependent patients and 96 age- and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Impact of comorbid psychiatric disorders on the outcome of substance abusers: a six year prospective follow-up in two Norwegian counties

PubMed Central

Landheim, Anne Signe; Bakken, Kjell; Vaglum, Per

2006-01-01

Background Most help-seeking substance abusers have comorbid psychiatric disorders. The importance of such disorders for the long-term course of substance abuse is, however, still unclear. The aim of this paper is to describe six-year outcomes regarding death and relapse among alcoholics and poly-substance abusers and to analyse the predictive value of lifetime psychiatric disorders on relapse. Methods A consecutive sample of substance-dependent patients who received treatment in two counties in Norway (n = 287) was followed up after approximately six years. Information on socio-demographics, Axis I (CIDI) and II disorders (MCMI-II) and mental distress (HSCL-25) was gathered at baseline. At follow-up, detailed information regarding socio-demographics, use of substances (AUDIT and DUDIT) and mental distress (HSCL-25) was recorded (response rate: 63%). Results At six-year follow-up, 11% had died, most often male alcoholics (18%). Among the surviving patients, 70% had drug or alcohol related problems the year prior to follow-up. These patients were, classified as "relapsers". There were no significant differences in the relapse rate between women and men and among poly-substance abusers and alcoholics. The relapsers had an earlier onset of a substance use disorder, and more frequently major depression and agoraphobia. Multivariate analysis indicated that both psychiatric disorders (major depression) and substance use factors (early onset of a substance use disorder) were independent predictors of relapse. Conclusion For reducing the risk of long-term relapse, assessment and treatment of major depression (and agoraphobia) are important. In addition, we are in need of a comprehensive treatment and rehabilitation program that also focuses on the addictive behaviour. PMID:17054775

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

PubMed

Zois, E; Vollstädt-Klein, S; Hoffmann, S; Reinhard, I; Charlet, K; Beck, A; Jorde, A; Kirsch, M; Walter, H; Heinz, A; Kiefer, F

2017-10-01

Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence

PubMed Central

Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

2016-01-01

ABSTRACT Background: Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. Case presentation: A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. Discussion: CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. Conclusion: In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration. PMID:27105248

Bridging the gap: using microsociological theory to understand how expressed emotion predicts clinical outcomes.

PubMed

Stanhope, Victoria; Solomon, Phyllis

2007-06-01

Research has shown that expressed emotion (EE) among families is a strong predictor of relapse for people with severe mental illness. Recent studies have also found the presence of EE in consumer-provider relationships. Despite high consistency in the findings related to EE and relapse, the concept has weak validity as little is known about how exactly it triggers relapse. Microsociological theory provides a framework with which to analyze social interaction and, more specifically, understand how interactions relate to the emotions of pride and shame. By identifying the components of interaction rituals, the theory provides insight into the key processes underlying EE and demonstrates how methodologies based on direct observation have the potential to measure EE with greater validity. This article describes how microsociological theory can be applied to the concept of EE.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans

PubMed Central

Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

2017-01-01

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to non-alcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent pre-morbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. PMID:28394145

Lorenz system in the thermodynamic modelling of leukaemia malignancy.

PubMed

Alexeev, Igor

2017-05-01

The core idea of the proposed thermodynamic modelling of malignancy in leukaemia is entropy arising within normal haematopoiesis. Mathematically its description is supposed to be similar to the Lorenz system of ordinary differential equations for simplified processes of heat flow in fluids. The hypothetical model provides a description of remission and relapse in leukaemia as two hierarchical and qualitatively different states of normal haematopoiesis with their own phase spaces. Phase space transition is possible through pitchfork bifurcation, which is considered the common symmetrical scenario for relapse, induced remission and the spontaneous remission of leukaemia. Cytopenia is regarded as an adaptive reaction of haematopoiesis to an increase in entropy caused by leukaemia clones. The following predictions are formulated: a) the percentage of leukaemia cells in marrow as a criterion of remission or relapse is not necessarily constant but is a variable value; b) the probability of remission depends upon normal haematopoiesis reaching bifurcation; c) the duration of remission depends upon the eradication of leukaemia cells through induction or consolidation therapies; d) excessively high doses of chemotherapy in consolidation may induce relapse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhanced pain perception prior to smoking cessation is associated with early relapse.

PubMed

Nakajima, Motohiro; al'Absi, Mustafa

2011-09-01

Accumulated evidence suggests that nicotine induces analgesia, and endogenous pain regulatory mechanisms may be altered by chronic smoking. The extent to which individual differences in pain perception are related to smokers' ability to abstain from smoking has not been directly examined. Seventy-one smokers who were interested in quitting completed a pre-cessation laboratory session which included the cold pressor test (CPT). Pain ratings were collected during and after CPT. Also, mood changes, cardiovascular measures, and salivary cortisol samples were evaluated prior to, during, and after CPT. Participants attended 4 weekly follow-up assessment sessions after their quit day. Cox regression analysis revealed that higher pain ratings during and after CPT predicted greater risk for smoking relapse. These results remained significant after affective and physiological responses to CPT were controlled, suggesting that pain ratings prior to smoking cessation are potentially useful in identifying smokers who are at greater risk of early smoking relapse and may reflect underlying putative risk for nicotine dependence and relapse. Copyright © 2011 Elsevier B.V. All rights reserved.

A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data.

PubMed

Spelman, Tim; Gray, Orla; Lucas, Robyn; Butzkueven, Helmut

2015-12-09

This report describes a novel Stata-based application of trigonometric regression modelling to 55 years of multiple sclerosis relapse data from 46 clinical centers across 20 countries located in both hemispheres. Central to the success of this method was the strategic use of plot analysis to guide and corroborate the statistical regression modelling. Initial plot analysis was necessary for establishing realistic hypotheses regarding the presence and structural form of seasonal and latitudinal influences on relapse probability and then testing the performance of the resultant models. Trigonometric regression was then necessary to quantify these relationships, adjust for important confounders and provide a measure of certainty as to how plausible these associations were. Synchronization of graphing techniques with regression modelling permitted a systematic refinement of models until best-fit convergence was achieved, enabling novel inferences to be made regarding the independent influence of both season and latitude in predicting relapse onset timing in MS. These methods have the potential for application across other complex disease and epidemiological phenomena suspected or known to vary systematically with season and/or geographic location.

Expression of FAS-L Differs from Primary to Relapsed Low-grade Gliomas and Predicts Progression-free Survival.

PubMed

Werner, Jan-Michael; Kuhl, Saskia; Stavrinou, Pantelis; Röhn, Gabriele; Krischek, Boris; Blau, Tobias; Goldbrunner, Roland; Timmer, Marco

2017-12-01

The tumor necrosis factor FAS is overexpressed in high-grade gliomas (HGG). Only little is known about FAS or FAS ligand (FAS-L) in low-grade gliomas (LGG). We explored FAS/FAS-L expression in LGG, focusing on differences in primary and relapsed LGG and on its prognostic value. A total of 133 glioma samples (73 LGG, 60 HGG) were collected. The LGG samples included 15 matched pairs of primary and relapsed tumors. RT-PCR was performed to measure FAS/FAS-L expression, using subunit A, flavoprotein variant (SDHA) as housekeeper. Clinical data included progression free- (PFS) and overall survival (OS). LGG showed significantly lower FAS but higher FAS-L expression than HGG. The FAS-L expression was higher in primary compared to relapsed LGG and had a positive prognostic value concerning PFS (median 45.20 vs. 31.37 months). FAS-L could act as a prognostic marker and potential target in primary LGG. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Mobile kidney pain provocation ultrasonography before surgery for symptomatic mobile kidney: A prospective study of 43 consecutive patients.

PubMed

Arnerlöv, Conny; Söderström, Minette; Öhberg, Lars

2016-01-01

The aim of this study was to evaluate whether mobile kidney pain provocation ultrasonography together with intravenous pyelography in supine and standing positions and a full medical history can confirm the diagnosis of the clinical condition of symptomatic mobile kidney and aid the selection of patients for surgical treatment. In a consecutive study, 43 patients with the clinical picture of symptomatic mobile kidney, a positive mobile kidney pain provocation ultrasonography and a renal descent of at least 2 lumbar vertebral heights on intravenous pyelography in the standing position, were operated on with nephropexy. Patients' pain relief after nephropexy was evaluated by clinical follow-up, a questionnaire and visual analogue scale (VAS) scoring. Reduction of pain after nephropexy was associated with a significant decrease in VAS scoring from a median of 8 (range 4-10) preoperatively to a median of 0 (range 0-7) postoperatively (p < 0.001). Thirty-four patients (79%) were cured of their pain and seven patients (16%) experienced substantial relief from their pain symptoms. In two patients (5%) the symptoms were unchanged. The results indicate that mobile kidney pain provocation ultrasonography and intravenous pyelography in supine and standing positions can verify the diagnosis of symptomatic mobile kidney and aid the selection of patients who will benefit from nephropexy.

Intimate partner violence perpetration corresponds to a dorsal-ventral gradient in medial PFC reactivity to interpersonal provocation.

PubMed

Chester, David S; DeWall, C Nathan

2018-01-22

Intimate partner violence (IPV) perpetration is often preceded by perceived interpersonal provocations such as slights, insults, and rejections. Yet the neural mechanisms that link provocation to IPV remain unclear. In the context of interactions with strangers, the medial prefrontal cortex (MPFC) has been repeatedly shown to respond to provocation, with more dorsal activation associated with more aggressive reactions and more ventral activation associated with less aggressive reactions. We used functional brain imaging to test whether this dorsal-ventral MPFC reactivity gradient would also correlate with greater aggression towards an unexamined target: intimate partners. To do so, 61 undergraduates (27.87% male, age range: 18-22) reported whether they had ever committed various acts of IPV perpetration (e.g., punching, hitting, shoving) and then were repeatedly provoked by a stranger while undergoing functional MRI (fMRI) scanning. Individuals with a disproportionately dorsal, rather than ventral, MPFC response were more likely to have perpetrated IPV and had perpetrated more kinds of IPV, even when controlling for gender. These findings provide further evidence that the dorsal-ventral MPFC gradient is a critical, biological indicator of whether an individual is more or less likely to react aggressively and suggest new avenues for understanding and potentially preventing IPV perpetration.

State narcissism and aggression: The mediating roles of anger and hostile attributional bias.

PubMed

Li, Caina; Sun, Ying; Ho, Man Yee; You, Jin; Shaver, Phillip R; Wang, Zhenhong

2016-07-01

Prior research has documented a relationship between narcissism and aggression but has focused only on dispositional narcissism without considering situational factors that may increase narcissism temporarily. This study explored the possibility that an increase in state narcissism would foster aggressive responding by increasing anger and hostile attributional bias following unexpected provocation among 162 college students from China. We created a guided-imagination manipulation to heighten narcissism and investigated its effects on anger, aroused hostile attribution bias, and aggressive responses following a provocation with a 2 (narcissism/neutral manipulation) × 2 (unexpected provocation/positive evaluation condition) between-subjects design. We found that the manipulation did increase self-reported state narcissism. The increase in state narcissism in turn heightened aggression, and this relation was mediated by increased anger. Regardless of the level of state narcissism, individuals were more aggressive after being provoked and this effect of provocation was mediated by hostile attributional bias. The findings indicate that narcissism can be temporarily heightened in a nonclinical sample of individuals, and that the effect of state narcissism on aggression is mediated by anger. Differences between state and trait narcissism and possible influences of culture are discussed. Aggr. Behav. 42:333-345, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

[Prodromal symptoms in schizophrenic relapse: A descriptive and comparative study].

PubMed

Bouhlel, S; Jones, Y; Khelifa, E; Msolly, M; Melki, W; El-Hechmi, Z

2012-10-01

Schizophrenia is a severe, chronic psychiatric disorder. After recovery from a first psychotic episode, 70% of patients have exacerbations. These exacerbations are preceded in 66 to 100% of cases by early signs. Prevention of relapses is the main object of dealing with schizophrenia. In fact, after a psychotic relapse, 17% of patients develop residual symptoms which did not exist before the relapse. Moreover, symptoms resistant to antipsychotics appear in 35% of patients after a relapse. Each relapse increases the risk of future relapses. Finally, the cost of treating patients with relapses is four times higher than in patients without relapses. Prevention of relapses is possible if we detect early signs. In fact, when specific interventions are applied in time, relapses can be avoided. Surprisingly, there is a scarcity of data on prodromal symptoms of schizophrenic relapses in the literature. In this study, we aimed to describe early signs of schizophrenic relapses, which are comparatively more frequent than those in stabilized outpatients. We conducted a retrospective, descriptive and comparative trial. We included 30 patients with schizophrenia who had recently experienced a psychotic relapse and a member of their families. We also included a control group of 30 stabilized outpatients with schizophrenia. All of the patients were diagnosed schizophrenic according to the DSM IV and had no secondary diagnosis. Only patients aged from 18 to 55 years and having an illness with an episodic evolution were included. The relapse group must have had a period off illness of more than one year and duration of the last remission greater than 3 months. We built a structured interview based on the data of the literature on early symptoms of relapses and on our clinical experience. It contained 93 items describing symptoms and feelings relevant to the period of relapse. The interview lasted about 1h. We collected demographic information from both groups. The relapse group was composed of 21 men and nine women. Their average age was 34 years and their level of education was 9.3 years. The mean number of hospitalizations was 3.8 and 73.3% of patients had interrupted their medication. The stabilized outpatients group included 25 men and five women with an average age of 40.3 years. The mean level of education was 8.3 years, the number of hospitalizations was 2.7 and 16.7% of patients had interrupted their medication. The mean time interval between the beginning of symptoms and the need for hospitalization was 160.5 days. The more frequent symptoms in the relapse group than in stabilized patients were: overinvested ideas/delusions (93.3% of relapsing patients), trouble sleeping (80%), symptoms of disorganization (80%), and excitement/mood changes (73.3%). Globally, non-specific symptoms precede specific symptoms (149.4 days vs. 94.8 days). The earlier signs were influence syndrome (113.4 days before relapse), verbal aggressions against others (108.1 days) and suicidal thoughts (94.8 days). The latest signs were physical aggression against others (37.3 days), unmotivated smiles (35.4 days), aggression against self (35 days), strange thoughts (30.7 days) and breaking things (25.3 days). The time between perception of symptoms and hospitalization in schizophrenic patients in this study was very long (approximately 6 months). Non-psychotic prodromal symptoms precede psychotic symptoms. We recommend a major focus on teaching the patient and his/her family how to recognize early signs of decompensation and what steps to take to ensure effective treatment. We also recommend further research to determine the predictive positive value of early signs of relapse. Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Prediction of acute GVHD and relapse by metabolic biomarkers after allogeneic hematopoietic stem cell transplantation.

PubMed

Wu, Xiaojin; Xie, Yiyu; Wang, Chang; Han, Yue; Bao, Xiebing; Ma, Shoubao; Yilmaz, Ahmet; Yang, Bingyu; Ji, Yuhan; Xu, Jinge; Liu, Hong; Chen, Suning; Zhang, Jianying; Yu, Jianhua; Wu, Depei

2018-05-03

There are very few studies investigating metabolic biomarkers to predict acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Metabolic models can provide a framework for analyzing the information-rich omics data sets in this setting. Four hundred and fifty-six samples from one hundred and fourteen consecutive patients who underwent HSCT from January 2012 to May 2014 were collected for this study. The changes in serum metabolite levels were investigated using a gas chromatography-mass spectrometry-based metabolomics approach and underwent statistical analysis. Significant metabolic changes were observed on day 7. The stearic acid/palmitic acid (SA/PA) ratio was effective in the diagnosis of grade II-IV aGVHD. Multivariate analysis showed that patients with high SA/PA ratios on day 7 after HSCT were less likely to develop II-IV aGVHD than patients with low SA/PA ratios (odds ratio [OR] = 0.06, 95% CI 0.02-0.18, P < 0.001). After the adjustment for clinical characteristics, the SA/PA ratio had no significant effect on overall survival (hazard ratio [HR] = 1.95, 95% CI 0.92-4.14, P = 0.08), and patients in the high SA/PA ratio group were significantly more likely to relapse than those in the low ratio group (HR = 2.26, 95% CI 1.04-4.91, P = 0.04). Our findings suggest that the SA/PA ratio on day 7 after HSCT is an excellent biomarker to predict both aGVHD and relapse. The serum SA/PA ratio measured on day 7 after transplantation may improve risk stratification for aGVHD and relapse after allogeneic stem cell transplantation. National Natural Science Foundation of China (81470346, 81773361), Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Natural Science Foundation (BK20161204), Innovation Capability Development Project of Jiangsu Province (BM2015004), Jiangsu Medical Junior Talent Person award (QNRC2016707), and NIH (AI129582 and NS106170).

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

PubMed

Mackenzie, P; Pryor, D; Burmeister, E; Foote, M; Panizza, B; Burmeister, B; Porceddu, S

2014-10-01

To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

PubMed

Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas

2012-08-01

In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.

A comparison of skin endpoint titration and skin-prick testing in the diagnosis of allergic rhinitis.

PubMed

Gungor, Anil; Houser, Steven M; Aquino, Benjamin F; Akbar, Imran; Moinuddin, Rizwan; Mamikoglu, Bulent; Corey, Jacquelynne P

2004-01-01

Among the many methods of allergy diagnosis are intradermal testing (IDT) and skin-prick testing (SPT). The usefulness of IDT has been called into question by some authors, while others believe that studies demonstrating that SPT was superior might have been subject to bias. We conducted a study to compare the validity of SPT and IDT--specifically, the skin endpoint titration (SET) type of IDT--in diagnosing allergic rhinitis. We performed nasal provocation testing on 62 patients to establish an unbiased screening criterion for study entry. Acoustic rhinometric measurements of the nasal responses revealed that 34 patients tested positive and 28 negative. All patients were subsequently tested by SET and SPT. We found that SPT was more sensitive (85.3 vs 79.4%) and more specific (78.6 vs 67.9%) than SET as a screening procedure. The positive predictive value of SPT was greater than that of SET (82.9 vs 75.0%), as was the negative predictive value (81.5 vs 73.0%). None of these differences was statistically significant; because of the relatively small sample size, our study was powered to show only equivalency. The results of our study suggest that the information obtained by the SET method of IDT is comparable to that obtained by SPT in terms of sensitivity, specificity, and overall performance and that both SET and SPT correlate well with nasal provocation testing for ragweed. Therefore, the decision as to which to use can be based on other factors, such as the practitioner's training, the desire for quantitative results, the desire for rapid results, and the type of treatment (i.e., immunotherapy or pharmacotherapy) that is likely to be chosen on the basis of test results.

Targeted intervention: Computational approaches to elucidate and predict relapse in alcoholism.

PubMed

Heinz, Andreas; Deserno, Lorenz; Zimmermann, Ulrich S; Smolka, Michael N; Beck, Anne; Schlagenhauf, Florian

2017-05-01

Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood. Based on the reinforcing effects of drugs of abuse, animal experiments showed that drug, cue and stress exposure affect Pavlovian and instrumental learning processes, which can increase salience of drug cues and promote habitual drug intake. In humans, computational approaches can help to quantify changes in key learning mechanisms during the development and maintenance of alcohol dependence, e.g. by using sequential decision making in combination with computational modeling to elucidate individual differences in model-free versus more complex, model-based learning strategies and their neurobiological correlates such as prediction error signaling in fronto-striatal circuits. Computational models can also help to explain how alcohol-associated cues trigger relapse: mechanisms such as Pavlovian-to-Instrumental Transfer can quantify to which degree Pavlovian conditioned stimuli can facilitate approach behavior including alcohol seeking and intake. By using generative models of behavioral and neural data, computational approaches can help to quantify individual differences in psychophysiological mechanisms that underlie the development and maintenance of AUD and thus promote targeted intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

PubMed

Fotopoulou, Christina; Sehouli, Jalid; Ewald-Riegler, Nina; de Gregorio, Nikolaus; Reuss, Alexander; Richter, Rolf; Mahner, Sven; Kommoss, Friedrich; Schmalfeldt, Barbara; Fehm, Tanja; Hanker, Lars; Wimberger, Pauline; Canzler, Ulrich; Pfisterer, Jacobus; Kommoss, Stefan; Hauptmann, Steffen; du Bois, Andreas

2015-09-01

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

A prospective multicenter study of factors associated with hospital admission among adults with acute asthma.

PubMed

Weber, Ellen J; Silverman, Robert A; Callaham, Michael L; Pollack, Charles V; Woodruff, Prescott G; Clark, Sunday; Camargo, Carlos A

2002-10-01

We sought to determine patient characteristics associated with hospital admission after emergency treatment for asthma, and whether disposition guidelines are followed. We performed a prospective multicenter cohort study involving 64 emergency departments in the United States and Canada. Consecutive adult patients with asthma exacerbations were interviewed, and their charts were reviewed using standardized protocols. Telephone follow-up at 2 weeks determined relapse. Of 1805 patients, 363 (20%; 95% confidence interval [CI]: 18% to 22%) were hospitalized. Among patients with severe exacerbations (final peak flow <50% of predicted), 122 (49%; 95% CI: 43% to 55%) were hospitalized. Admission was associated with final peak flow, female sex, nonwhite race, severity of chronic illness, and severity of exacerbation. Admission predictors were similar regardless of hospital funding, region, or size. Among patients with mild or moderate exacerbations of asthma (peak flow >or=50% predicted), the likelihood of admission was associated significantly with the number of predefined risk factors for death from asthma. Of patients who were discharged from the emergency department, 62 (5%; 95% CI: 4% to 6%) relapsed within 72 hours. Relapse was not associated with final peak flow (P = 0.39). Associations between patient characteristics and disposition were similar across sites. Despite guidelines to the contrary, half of patients with final peak flow <50% were discharged. After emergency department treatment and discharge, short-term relapse was uncommon among patients with asthma, suggesting that strict peak flow cutoffs may be unnecessary if risk factors in patients with mild or moderate exacerbations are considered.

Hypersomnia Subtypes, Sleep and Relapse in Bipolar Disorder

PubMed Central

Kaplan, Katherine A.; McGlinchey, Eleanor L.; Soehner, Adriane; Gershon, Anda; Talbot, Lisa S.; Eidelman, Polina; Gruber, June; Harvey, Allison G.

2015-01-01

Background Though poorly defined, hypersomnia is associated with negative health outcomes, and new-onset and recurrence of psychiatric illness. Lack of definition impedes generalizability across studies. The present research clarifies hypersomnia diagnoses in bipolar disorder by exploring possible subgroups and their relationship to prospective sleep data and relapse into mood episodes. Methods A community sample of 159 adults (ages 18–70) with bipolar spectrum diagnoses, euthymic at study entry, were included. Self-report inventories and clinician-administered interviews determined features of hypersomnia. Participants completed sleep diaries and wore wrist actigraphy at home to obtain prospective sleep data. Approximately seven months later, psychiatric status was reassessed. Factor analysis and latent profile analysis explored empirical groupings within hypersomnia diagnoses. Results Factor analyses confirmed two separate subtypes of hypersomnia (‘long sleep’ and ‘excessive sleepiness’) that were uncorrelated. Latent profile analyses suggested a four-class solution, with ‘long sleep’ and ‘excessive sleepiness’ again representing two separate classes. Prospective sleep data suggested that the sleep of ‘long sleepers’ is characterized by long time in bed, not long sleep duration. Longitudinal assessment suggested that ‘excessive sleepiness’ at baseline predicted mania/hypomania relapse. Conclusions This study is the largest of hypersomnia to include objective sleep measurement, and refines our understanding of classification, characterization and associated morbidity. Hypersomnia appears to be comprised of two separate subgroups, long sleep and excessive sleepiness. Long sleep is characterized primarily by long bedrest duration. Excessive sleepiness is not associated with longer sleep or bedrest, but predicts relapse to mania/hypomania. Understanding these entities has important research and treatment implications. PMID:25515854

Evaluation of the Lactate-to-N-Acetyl-aspartate Ratio Defined With Magnetic Resonance Spectroscopic Imaging Before Radiation Therapy as a New Predictive Marker of the Site of Relapse in Patients With Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deviers, Alexandra; UMR; INP

Purpose: Because lactate accumulation is considered a surrogate for hypoxia and tumor radiation resistance, we studied the spatial distribution of the lactate-to-N-acetyl-aspartate ratio (LNR) before radiation therapy (RT) with 3D proton magnetic resonance spectroscopic imaging (3D-{sup 1}H-MRSI) and assessed its impact on local tumor control in glioblastoma (GBM). Methods and Materials: Fourteen patients with newly diagnosed GBM included in a phase 2 chemoradiation therapy trial constituted our database. Magnetic resonance imaging (MRI) and MRSI data before RT were evaluated and correlated to MRI data at relapse. The optimal threshold for tumor-associated LNR was determined with receiver-operating-characteristic (ROC) curve analysis ofmore » the pre-RT LNR values and MRI characteristics of the tumor. This threshold was used to segment pre-RT normalized LNR maps. Two spatial analyses were performed: (1) a pre-RT volumetric comparison of abnormal LNR areas with regions of MRI-defined lesions and a choline (Cho)-to- N-acetyl-aspartate (NAA) ratio ≥2 (CNR2); and (2) a voxel-by-voxel spatial analysis of 4,186,185 voxels with the intention of evaluating whether pre-RT abnormal LNR areas were predictive of the site of local recurrence. Results: A LNR of ≥0.4 (LNR-0.4) discriminated between tumor-associated and normal LNR values with 88.8% sensitivity and 97.6% specificity. LNR-0.4 voxels were spatially different from those of MRI-defined lesions, representing 44% of contrast enhancement, 64% of central necrosis, and 26% of fluid-attenuated inversion recovery (FLAIR) abnormality volumes before RT. They extended beyond the overlap with CNR2 for most patients (median: 20 cm{sup 3}; range: 6-49 cm{sup 3}). LNR-0.4 voxels were significantly predictive of local recurrence, regarded as contrast enhancement at relapse: 71% of voxels with a LNR-0.4 before RT were contrast enhanced at relapse versus 10% of voxels with a normal LNR (P<.01). Conclusions: Pre-RT LNR-0.4 in GBM indicates tumor areas that are likely to relapse. Further investigations are needed to confirm lactate imaging as a tool to define additional biological target volumes for dose painting.« less

Hostile attribution biases for relationally provocative situations and event-related potentials.

PubMed

Godleski, Stephanie A; Ostrov, Jamie M; Houston, Rebecca J; Schlienz, Nicolas J

2010-04-01

This exploratory study investigates how hostile attribution biases for relationally provocative situations may be related to neurocognitive processing using the P300 event-related potential. Participants were 112 (45 women) emerging adults enrolled in a large, public university in upstate New York. Participants completed self-report measures on relational aggression and hostile attribution biases and performed an auditory perseveration task to elicit the P300. It was found that hostile attribution biases for relational provocation situations was associated with a larger P300 amplitude above and beyond the role of hostile attribution biases for instrumental situations, relational aggression, and gender. Larger P300 amplitude is interpreted to reflect greater allocation of cognitive resources or enhanced "attending" to salient stimuli. Implications for methodological approaches to studying aggression and hostile attribution biases and for theory are discussed, as well as implications for the fields of developmental psychology and psychopathology. Copyright 2010 Elsevier B.V. All rights reserved.

Evaluation of 5-fluorouracil metabolic enzymes as predictors of response to adjuvant chemotherapy outcomes in patients with stage II/III colorectal cancer: a decision-curve analysis.

PubMed

Shigeta, Kohei; Ishii, Yoshiyuki; Hasegawa, Hirotoshi; Okabayashi, Koji; Kitagawa, Yuko

2014-12-01

The effectiveness of 5-fluorouracil (5-FU)-based adjuvant chemotherapy is reported in patients with colorectal cancer (CRC), but the usefulness of 5-FU metabolic enzymes as predictive biomarkers of the efficacy of this chemotherapy remains unclear. This study aims to verify whether 5-FU metabolic enzymes are predictive biomarkers in the clinical setting of adjuvant chemotherapy for stage II/III CRC. In total, 179 patients with stage II/III CRC who were treated at our institute between 2000 and 2010 were enrolled. Messenger RNA (mRNA) expression of major 5-FU metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase (TP), orotate phosphoribosyl transferase, and β-actin (control) was evaluated using the Danenberg Tumor Profile method. mRNA expression and other clinicopathological data were investigated with regard to CRC relapse. A total of 78 patients underwent surgery alone, while 101 underwent adjuvant chemotherapy (5-FU plus leucovorin [LV] or tegafur plus uracil /LV) following surgery. Relapse-free survival was longer and risk of recurrence was lower in association with high TP mRNA expression than in association with low TP mRNA expression in the adjuvant chemotherapy group (hazard ratio 0.66; 95 % confidence interval 0.47-0.92; p = 0.016), but not in the surgery alone group. mRNA expression of no other enzymes was associated with relapse in both groups. In decision-curve analyses, the predictive efficiency of TP mRNA expression plus clinicopathological factors was slightly better than that of clinicopathological factors only. TP mRNA expression in tumors predicted the effects of adjuvant chemotherapy for stage II/III CRC, although the beneficial effects were marginal.

Affective and Cognitive Orientations in Intergroup Perception

PubMed Central

Wolf, Lukas J.; von Hecker, Ulrich; Maio, Gregory R.

2017-01-01

Three studies examined the role of need for affect (NFA) and need for cognition (NFC) in intergroup perception. We hypothesized that NFA predicts a preference for stereotypically warm groups over stereotypically cold groups, whereas NFC predicts a preference for stereotypically competent groups over stereotypically incompetent groups. Study 1 supported these hypotheses for attitudes toward stereotypically ambivalent groups, which are stereotyped as high on one of the trait dimensions (e.g., high warmth) and low on the other (e.g., low competence), but not for stereotypically univalent groups, which are seen as high or low on both dimensions. Studies 2 and 3 replicated this pattern for stereotypically ambivalent groups, and yielded provocative evidence regarding several putative mechanisms underlying these associations. Together, these findings help integrate and extend past evidence on attitude-relevant individual differences with research on intergroup perception. PMID:28903673

Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.

PubMed

Desjonquères, A; Chevallier, P; Thomas, X; Huguet, F; Leguay, T; Bernard, M; Bay, J-O; Tavernier, E; Charbonnier, A; Isnard, F; Hunault, M; Turlure, P; Renaud, M; Bastié, J-N; Himberlin, C; Lepretre, S; Lioure, B; Lhéritier, V; Asnafi, V; Beldjord, K; Lafage-Pochitaloff, M; Béné, M C; Ifrah, N; Dombret, H

2016-12-09

The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.

Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking.

PubMed

Chesworth, Rose; Corbit, Laura H

2017-01-01

One of the principal barriers to overcoming addiction is the propensity to relapse, even after months or years of abstinence. Relapse can be precipitated by cues and contexts associated with drug use; thus, decreasing the conditioned properties of these cues and contexts may assist in preventing relapse. The predictive power of drug cues and contexts can be reduced by repeatedly presenting them in the absence of the drug reinforcer, a process known as extinction. The potential of extinction to limit relapse has generated considerable interest and research over the past few decades. While pre-clinical animal models suggest extinction learning assists relapse prevention, treatment efficacy is often lacking when extinction learning principles are translated into clinical trials. Conklin and Tiffany (Addiction, 2002) suggest the lack of efficacy in clinical practice may be due to limited translation of procedures demonstrated through animal research and propose several methodological improvements to enhance extinction learning for drug addiction. This review will examine recent advances in the behavioural and pharmacological manipulation of extinction learning, based on research from pre-clinical models. In addition, the translation of pre-clinical findings-both those suggested by Conklin and Tiffany () and novel demonstrations from the past 13 years-into clinical trials and the efficacy of these methods in reducing craving and relapse, where available, will be discussed. Finally, we highlight areas where promising pre-clinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods. © 2015 Society for the Study of Addiction.

Hip range of motion and provocative physical examination tests reliability and agreement in asymptomatic volunteers

PubMed Central

Prather, H; Harris-Hayes, M; Hunt, D; Steger-May, K; Mathew, V; Clohisy, JC

2012-01-01

Objective The objectives of this study are the following: 1) report passive hip ROM in asymptomatic young adults, 2) report the intra-tester and inter-tester reliability of hip ROM measurements among testers of multiple disciplines, 3) report the results of provocative hip tests and tester agreement. Design descriptive epidemiology study Setting tertiary university Participants Twenty-eight young adult volunteers without musculoskeletal symptoms, history of disorder or surgery involving the lumbar spine or lower extremities were enrolled and completed the study. Methods Asymptomatic young adult volunteers completed questionnaires and were examined by two blinded examiners during a single session. The testers were physical therapists and physicians. Hip range of motion and provocative tests were completed by both examiners on each hip. Main Outcome Measurements Inter and intra-rater reliability for ROM and agreement for provocative tests was determined. Results Twenty-eight asymptomatic adults with mean age 31 years old (range 18–51 years) and mean modified Harris Hip Score of 99.5 ± 1.5 and UCLA Activity score of 8.8 ± 1.2 completed the study. Intra-rater agreement was excellent for all hip range of motion measurements, with intraclass correlation coefficients (ICCs) ranging from 0.76 to 0.97 with similar agreement if the examiner was a physical therapist or a physician. Excellent inter-rater reliability was found for hip flexion ICC 0.87 (95% CI 0.78 to 0.92), supine internal rotation ICC 0.75 (95% CI 0.60 to 0.84) and prone internal rotation ICC 0.79 (95% CI 0.66 to 0.87). The least reliable measurements were supine hip abduction (ICC 0.34) and supine external rotation (ICC 0.18). Agreement between examiners ranged from 96–100% for provocative hip tests which included the hip impingement, resisted straight leg raise, FABER/Patrick’s and log roll tests. Conclusions Specific hip ROM measures show excellent inter-rater reliability and provocative hip tests show good agreement among multiple examiners and medical disciplines. Further studies are needed to assess the utilization of these measurements and tests as a part of a hip screening examination to assess for young adults at risk intra-articular hip disorders prior to the onset of degenerative changes. PMID:20970757

Clinical significance of minimal residual disease at day 15 and at the end of therapy in childhood acute lymphoblastic leukaemia.

PubMed

Sutton, Rosemary; Venn, Nicola C; Tolisano, Jonathan; Bahar, Anita Y; Giles, Jodie E; Ashton, Lesley J; Teague, Lochie; Rigutto, Gemma; Waters, Keith; Marshall, Glenn M; Haber, Michelle; Norris, Murray D

2009-08-01

Detection of minimal residual disease (MRD) after induction and consolidation therapy is highly predictive of outcome for childhood acute lymphoblastic leukaemia (ALL) and is used to identify patients at high risk of relapse in several current clinical trials. To evaluate the prognostic significance of MRD at other treatment phases, MRD was measured by real-time quantitative polymerase chain reaction on a selected group of 108 patients enrolled on the Australian and New Zealand Children's Cancer Study Group Study VII including 36 patients with a bone marrow or central nervous system relapse and 72 matched patients in first remission. MRD was prognostic of outcome at all five treatment phases tested: at day 15 (MRD > or = 5 x 10(-2), log rank P < 0.0001), day 35 (> or =1 x 10(-2), P = 0.0001), 4 months (> or =5 x 10(-4), P < 0.0001), 12 months (MRD > or = 1 x 10(-4), P = 0.006) and 24 months (MRD > or = 1 x 10(-4), P < 0.0001). Day 15 was the best early MRD time-point to differentiate between patients with high, intermediate and low risk of relapse. MRD testing at 12 and particularly at 24 months, detected molecular relapses in some patients up to 6 months before clinical relapse. This raised the question of whether a strategy of late monitoring and salvage therapy will improve outcome.

Serotonin at the Nexus of Impulsivity and Cue Reactivity in Cocaine Addiction

PubMed Central

Cunningham, Kathryn A.; Anastasio, Noelle C.

2014-01-01

Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction. PMID:23850573

Life adversity is associated with smoking relapse after a quit attempt.

PubMed

Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

2016-09-01

Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal course of panic disorder with and without agoraphobia using the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

PubMed

Nay, William; Brown, Ruth; Roberson-Nay, Roxann

2013-06-30

Few naturalistic, longitudinal studies of panic disorder with and without agoraphobia (PD/PDA) exist, limiting our knowledge of the temporal rates of incidence, relapse, and chronicity, or the factors that predict category transition. Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) wave 1 (n=43,093) and wave 2 (n=34,653) were utilized to determine transitional rates, and predictors of category transitions, over a 3-year period. Analyses revealed very high 3-year remission rates for PD and PDA (75% and 67%, respectively), although relapse also was relatively frequent (PD=12%; PDA=21%). Logistic regression revealed previous history of panic attacks, generalized anxiety disorder/major depression (GAD/MDD), nicotine dependence, female sex, younger age, and major financial crises to be reliable predictors of incidence and relapse. The direction and magnitude of association of many predictor variables were similar for PD and PDA, with notable exceptions for social anxiety and romantic relationship factors. Clinicians should be aware of the relapsing-remitting nature of PD and PDA and, thus, take caution to not reduce or eliminate effective treatments prematurely. Similarly, the current study suggests clinicians pay particular attention to concurrent factors relevant to relapse in PD/PDA that may also be clinically addressed (e.g., co-morbid MDD/GAD and nicotine dependence). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The roles of ingroup identification and outgroup entitativity in intergroup retribution.

PubMed

Stenstrom, Douglas M; Lickel, Brian; Denson, Thomas F; Miller, Norman

2008-11-01

A new aspect of intergroup conflict was investigated- vicarious retribution-in which neither the agent of retribution nor the target of retribution are directly involved in the initial intergroup provocation. The underlying processes involved in vicarious intergroup retribution were tested correlationally (Study 1) and experimentally (Study 2). Both ingroup identification and outgroup entitativity predict the degree of vicarious retribution. In both studies, there was evidence of motivated cognition, specifically that highly identified individuals perceived the outgroup as higher in entitativity than individuals low in identification. Structural equation modeling demonstrated that part of the effect of identification on retribution against the outgroup was mediated through perceptions of entitativity.

Esophageal manometry in gastroesophageal reflux disease.

PubMed

Mello, Michael; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery. Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD. Copyright © 2014 Elsevier Inc. All rights reserved.

Reaching Out to Problem Anger: Assessing the Effectiveness of One-Day Cognitive Behavioural Workshops in a Community Setting in the UK.

PubMed

Illman, Nathan A; Brown, June S L

2016-09-01

Problem anger is frequently experienced by the general population and is known to cause significant problems for the individual and those around them. Whilst psychological treatments for problem anger are becoming increasingly established, this is still an under-researched area of mental health. We present an evaluation of a series of one-day anger management workshops for the public, targeting problem anger with a cognitive-behavioural approach. The main aim was to evaluate the effectiveness of a brief group-based anger intervention in terms of subjectively reported anger provocation levels and of depression and anxiety. Workshop participants completed a number of questionnaire measures at baseline before the intervention and at 1 month follow-up. The key questionnaires measured self-reported anger provocation levels (Novaco Anger Scale-Provocation Inventory), depressive symptomatology (PHQ-9) and symptoms of generalized anxiety (GAD-7). Change scores were analysed using repeated measures analyses. We found a significant reduction in anger provocation among workshop participants at 1 month follow-up (p = .03). Reductions in depression and anxiety were not statistically significant. We conclude that this brief psychoeducational anger intervention was effective in a small community sample and suggest future work should assess the effectiveness on similar brief interventions using a larger client group and examine outcomes on a broader range of anger measures.

Can conjunctival provocation test facilitate the diagnosis of food allergy in children?

PubMed

Krane Kvenshagen, B; Jacobsen, M; Halvorsen, R

2010-01-01

Food allergy is common in children, occurring in 5-7.5%. The diagnosis may, however, be difficult. Elevated IgE or positive skin prick test to a food allergen is often considered proof of allergy, but may represent sensitisation without clinical manifestations. For a precise diagnosis oral challenge is necessary, but this is often not performed because of risk of serious allergic reactions. The aim of this study was to evaluate whether conjunctival provocation test would facilitate the diagnosis of IgE-mediated food allergy. One hundred and forty-nine children with 174 possible diagnoses of food allergy were included. General examination, skin prick test and specific IgE were performed, as well as conjunctival provocation test of the suspected food allergen. Open food challenges and double-blind placebo controlled tests were performed in order to diagnose possible food allergy. Forty-six children with strongly positive conjunctival reactions (rubor, itching, oedema) to fifty food allergens were all proven to have allergy to the food in question. The children with negative conjunctival provocation tests showed no allergic reactions when challenged. We find that a strongly positive conjunctival reaction to a food allergen correlates well with true allergy. An oral challenge should be carefully performed. With a negative conjunctival test an oral challenge may safely be performed. Copyright © 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Influence of body mass index on the growth hormone response to provocative testing in short children without growth hormone deficiency.

PubMed

Lee, Jieun; Yoon, Juyoung; Kang, Min Jae; Lee, Young Ah; Lee, Seong Yong; Shin, Choong Ho; Yang, Sei Won

2013-09-01

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

Ergonovine-induced changes of coronary artery diameter in patients with nonsignificant coronary artery stenosis : relation with lipid profile.

PubMed

Nedeljkovic, Milan A; Ostojic, Miodrag C; Beleslin, Branko D; Nedeljkovic, Ivana; Milic, Natasa; Vukcevic, Vladan; Stojkovic, Sinisa; Saponjski, Jovica; Orlic, Dejan; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Giga, Vojislav; Petrasinovic, Zorica; Arandjelovic, Aleksandra; Beleslin, Biljana; Kanjuh, Vladimir

2007-06-01

Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.

Dimensions of depressive symptoms and smoking cessation.

PubMed

Leventhal, Adam M; Ramsey, Susan E; Brown, Richard A; LaChance, Heather R; Kahler, Christopher W

2008-03-01

Because different psychopathologic components of depressive symptoms may have distinct etiologies, examining their differential effects on smoking cessation may elucidate mechanisms underlying the smoking-depression relationship. Negative affect (NA), somatic features (SF), low positive affect/anhedonia (PA), and interpersonal disturbance (IP) have been identified as unique dimensions of depression that can be measured using the Center for Epidemiologic Studies Depression Scale (CESD). This study examined common and unique associations between CESD subscales and baseline smoking characteristics, nicotine withdrawal, and relapse in 157 participants enrolled in a smoking cessation trial for heavy social drinkers. Each dimension was univariately associated with negative and positive reinforcement smoking motives. Only SF had unique relations with tolerance smoking motives and univariate associations with nicotine dependence severity. Only PA predicted cessation-related changes in withdrawal symptoms on quit day. Analyses predicting abstinence at 8, 16, and 26 weeks post quit date showed that NA, SF, and PA each univariately predicted relapse, ps< or =.0083. Only low PA predicted poorer outcomes incrementally to the other dimensions, even when controlling for level of nicotine dependence, smoking frequency, and history of major depression, p = .0018. Interventions targeting anhedonia and low positive affect may be useful for smokers trying to quit.

Cognitive Therapy Skills Predict Cognitive Reactivity to Sad Mood Following Cognitive Therapy for Depression

PubMed Central

Strunk, Daniel R.; Adler, Abby D.; Hollars, Shannon N.

2013-01-01

Both patients’ competence in the coping skills taught in Cognitive Therapy (CT) and patients’ endorsement of dysfunctional cognitions following a sad mood induction (i.e., their cognitive reactivity) have been found to predict risk of relapse following a successful course of CT for depression. We examined the relationship between these constructs, specifically whether CT skills would be related to less cognitive reactivity following a mood induction among patients who responded to a course of CT. In a sample of 28 depressed patients, post-treatment CT skills were significantly related to less cognitive reactivity in response to a sad mood induction procedure (β = −.29). This relation was not accounted for by individual differences in mood reactivity. We discuss these findings as a key step in developing a more complete understanding of the role of CT coping skills and cognitive reactivity as markers of patients’ vulnerability to relapse. PMID:24363473

NEURAL SUBSTRATES OF CUE-REACTIVITY: ASSOCIATION WITH TREATMENT OUTCOMES AND RELAPSE

PubMed Central

Courtney, Kelly E.; Schacht, Joseph P.; Hutchison, Kent; Roche, Daniel J.O.; Ray, Lara A.

2016-01-01

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue-reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of relapse, and as a means to investigate psychosocial and pharmacological treatment effects on cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine, and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided. PMID:26435524

Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.

PubMed

Picardi, Marco; Pugliese, Novella; Cirillo, Michele; Zeppa, Pio; Cozzolino, Imma; Ciancia, Giuseppe; Pettinato, Guido; Salvatore, Claudia; Quintarelli, Concetta; Pane, Fabrizio

2014-07-01

To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma. Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs. A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography. US and chest radiography are diagnostic tools that enable effective, safe, and low-cost routine surveillance imaging for patients at high risk of Hodgkin lymphoma relapse. © RSNA, 2014.

The relationship between adult reactive and proactive aggression, hostile interpretation bias, and antisocial personality disorder.

PubMed

Lobbestael, Jill; Cima, Maaike; Arntz, Arnoud

2013-02-01

Reactive aggression (RA) refers to angry responses to provocation or frustration, while proactive aggression (PA) denotes nonemotional, instrumental, and unprovoked aggression. The current study examined personality-related and cognitive correlates of both aggressive types. Respectively, the predictive values of antisocial personality disorder (ASPD), and of hostile interpretation bias, which is the tendency to interpret ambiguous stimuli in a hostile manner, were studied. The sample consisted of n = 37 male adult patients with mixed diagnoses and n = 29 male nonpatients that responded to vignettes and pictures of ambiguous situations, using both open and closed answer formats. ASPD was assessed by means of the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II), and the Reactive Proactive Questionnaire (RPQ) measured RA and PA. Results showed that although both RA and PA types were predicted by ASPD traits, RA was additionally predicted by a hostile interpretation bias. These findings suggest that reducing hostile bias is a promising avenue for clinical treatment of ASPD-patients high in RA.

[Safety and efficacy of a new preservative-free levocabastine ophthalmic solution (Levofree®) using the conjunctival provocation test].

PubMed

Allaire, C; Siou-Mermet, R; Bassols, A

2012-09-01

To evaluate the safety and efficacy of preservative-free levocabastine 0.05 % ophthalmic solution compared to placebo (vehicle) and to preserved levocabastine 0.05 % ophthalmic suspension in the prevention of allergic conjunctivitis induced by a conjunctival provocation test. Ninety-two subjects (18-50 years) with a previous history of allergic conjunctivitis to pollen were randomised to receive either preservative-free levocabastine solution in one eye and preserved levocabastine suspension in the fellow eye (n=69), or preservative-free levocabastine in one eye and placebo in the fellow eye (n=23). One drop of each product was administered 10 minutes (visit 3) and 4 hours (visit 4) prior to the provocation test. The primary efficacy criterion was the sum of the itching and conjunctival hyperemia scores assessed at 3, 5 and 10 minutes after the provocation test. The safety evaluation included adverse events, visual acuity, intra-ocular pressure and study drug drop sensation. The efficacy of the preservative-free solution was significantly higher than that of placebo at all time points (P≤0.01) with one exception at visit 4 (3 minutes after the provocation test). It was significantly higher than that of the preserved suspension at visit 3, and equivalent at visit 4. The incidence of adverse events was lower with the preservative-free solution than with the preserved suspension. 94.2 % and 95.7 % subjects rated preservative-free levocabastine drop sensation as "good" or "very good" at visits 3 and 4 respectively, whereas these rates were 68.1 % and 63.8 % with preserved levocabastine. This difference between the two formulations was highly statistically significant (P<0.001). The efficacy of preservative-free levocabastine was superior to that of the placebo and of the preserved suspension at visit 3, at least as effective as the preserved suspension at visit 4, and better tolerated at each visit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Ondansetron and promethazine have differential effects on hypothermic responses to lithium chloride administration and to provocative motion in rats

PubMed Central

Guimaraes, Drielle D; Andrews, Paul L R; Rudd, John A; Braga, Valdir A; Nalivaiko, Eugene

2015-01-01

We recently reported that provocative motion (rotation in a home cage) causes hypothermic responses in rats, similar to the hypothermic responses associated with motion sickness in humans. Many stimuli inducing emesis in species with an emetic reflex also provoke hypothermia in the rat, therefore we hypothesized that a fall in body temperature may reflect a “nausea-like” state in these animals. As rats do not possess an emetic reflex, we employed a pharmacological approach to test this hypothesis. In humans, motion- and chemically-induced nausea have differential sensitivity to anti-emetics. We thus tested whether the hypothermia induced in rats by provocative motion (rotation at 0.7 Hz) and by the emetic LiCl (63 mg/kg i.p.) have a similar differential pharmacological sensitivity. Both provocations caused a comparable robust fall in core body temperature (−1.9 ± 0.3°C and −2.0 ± 0.2°C for chemical and motion provocations, respectively). LiCl−induced hypothermia was completely prevented by ondansetron (2mg/kg, i.p., a 5-HT3 receptor antagonist that reduces cancer chemotherapy-induced nausea and vomiting), but was insensitive to promethazine (10 mg/kg, i.p., a predominantly histamine-H1 and muscarinic receptor antagonist that is commonly used to treat motion sickness). Conversely, motion-induced hypothermia was unaffected by ondansetron but promethazine reduced the rate of temperature decline from 0.20 ± 0.02 to 0.11 ± 0.03°C/min (P < 0.05) with a trend to decrease the magnitude. We conclude that this differential pharmacological sensitivity of the hypothermic responses of vestibular vs. chemical etiology in rats mirrors the observations in other pre-clinical models and humans, and thus supports the idea that a “nausea-like” state in rodents is associated with disturbances in thermoregulation. PMID:27227074

The topographical model of multiple sclerosis

PubMed Central

Cook, Karin; De Nino, Scott; Fletcher, Madhuri

2016-01-01

Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way. The topographical model encapsulates 5 factors (localization of relapses and causative lesions; relapse frequency, severity, and recovery; and progression rate), visualized utilizing dynamic 3-dimensional renderings. The central hypothesis is that, like symptom recrudescence in Uhthoff phenomenon and pseudoexacerbations, progression clinically recapitulates prior relapse symptoms and unmasks previously silent lesions, incrementally revealing underlying lesion topography. The model uses real-time simulation software to depict disease course archetypes and illuminate several well-described but poorly reconciled phenomena including the clinical/MRI paradox and prognostic significance of lesion location and burden on disease outcomes. Utilization of this model could allow for earlier and more clinically precise identification of progressive MS and predictive implications can be empirically tested. PMID:27648465

Nonnormality and Divergence in Posttreatment Alcohol Use

PubMed Central

Witkiewitz, Katie; van der Maas, Han L. J.; Hufford, Michael R.; Marlatt, G. Alan

2007-01-01

Alcohol lapses are the modal outcome following treatment for alcohol use disorders, yet many alcohol researchers have encountered limited success in the prediction and prevention of relapse. One hypothesis is that lapses are unpredictable, but another possibility is the complexity of the relapse process is not captured by traditional statistical methods. Data from Project Matching Alcohol Treatments to Client Heterogeneity (Project MATCH), a multisite alcohol treatment study, were reanalyzed with 2 statistical methodologies: catastrophe and 2-part growth mixture modeling. Drawing on previous investigations of self-efficacy as a dynamic predictor of relapse, the current study revisits the self-efficacy matching hypothesis, which was not statistically supported in Project MATCH. Results from both the catastrophe and growth mixture analyses demonstrated a dynamic relationship between self-efficacy and drinking outcomes. The growth mixture analyses provided evidence in support of the original matching hypothesis: Individuals with lower self-efficacy who received cognitive behavior therapy drank far less frequently than did those with low self-efficacy who received motivational therapy. These results highlight the dynamical nature of the relapse process and the importance of the use of methodologies that accommodate this complexity when evaluating treatment outcomes. PMID:17516769

Does maintenance CBT contribute to long-term treatment response of panic disorder with or without agoraphobia? A randomized controlled clinical trial.

PubMed

White, Kamila S; Payne, Laura A; Gorman, Jack M; Shear, M Katherine; Woods, Scott W; Saksa, John R; Barlow, David H

2013-02-01

We examined the possibility that maintenance cognitive behavior therapy (M-CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either 9 monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. M-CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up. Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-month follow-up (hazards ratio = 1.15, p < .01). M-CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome for panic disorder with and without agoraphobia.

Does Maintenance CBT Contribute to Long-Term Treatment Response of Panic Disorder With or Without Agoraphobia? A Randomized Controlled Clinical Trial

PubMed Central

White, Kamila S.; Payne, Laura A.; Gorman, Jack M.; Shear, M. Katherine; Woods, Scott W.; Saksa, John R.; Barlow, David H.

2012-01-01

Objective To examine the possibility that maintenance cognitive behavior therapy (M–CBT) may improve the likelihood of sustained improvement and reduced relapse in a multi-site randomized controlled clinical trial of patients who met criteria for panic disorder with or without agoraphobia. Method Participants were all patients (N = 379) who first began an open trial of acute-phase CBT. Patients completing and responding to acute-phase treatment were randomized to receive either nine monthly sessions of M-CBT (n = 79) or assessment only (n = 78) and were then followed for an additional 12 months without treatment. Results M–CBT produced significantly lower relapse rates (5.2%) and reduced work and social impairment compared to the assessment only condition (18.4%) at a 21-month follow-up (MFU). Multivariate Cox proportional hazards models showed that residual symptoms of agoraphobia at the end of acute-phase treatment were independently predictive of time to relapse during 21-MFU (HR = 1.15, p < .01). Conclusions M–CBT aimed at reinforcing acute treatment gains to prevent relapse and offset disorder recurrence may improve long-term outcome in PD/A. PMID:23127290

Predictors of postretention stability of mandibular dental arch dimensions in patients treated with a lip bumper during mixed dentition followed by fixed appliances.

PubMed

Raucci, Gaetana; Pachêco-Pereira, Camila; Elyasi, Maryam; d'Apuzzo, Fabrizia; Flores-Mir, Carlos; Perillo, Letizia

2017-03-01

To identify which dental and/or cephalometric variables were predictors of postretention mandibular dental arch stability in patients who underwent treatment with transpalatal arch and lip bumper during mixed dentition followed by full fixed appliances in the permanent dentition. Thirty-one patients were divided into stable and relapse groups based on the postretention presence or absence of relapse. Intercuspid, interpremolar, and intermolar widths; arch length and perimeter; crowding; and lower incisor proclination were evaluated before treatment (T0), after lip bumper treatment (T1), after fixed appliance treatment (T2), and a minimum of 3 years after removal of the full fixed appliance (T3). Logistic regression analyses were performed to evaluate the effect of changes between T0 and T1, as predictive variables, on the occurrence of relapse at T3. The model explained 53.5 % of the variance in treatment stability and correctly classified 80.6 % of the sample. Of the seven prediction variables, intermolar and interpremolar changes between T0 and T1 (P = .024 and P = .034, respectively) were statistically significant. For every millimeter of increase in intermolar and interpremolar widths there was a 1.52 and 2.70 times increase, respectively, in the odds of having stability. There was also weak evidence for the effect of sex (P = .047). The best predictors of an average 4-year postretention mandibular dental arch stability after treatment with a lip bumper followed by full fixed appliances were intermolar and interpremolar width increases during lip bumper therapy. The amount of relapse in this crowding could be considered clinically irrelevant.

Prediction of minimal residual viremia in HCV type 1 infected patients receiving interferon-based therapy.

PubMed

Knop, Viola; Teuber, Gerlinde; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Hinrichsen, Holger; Gerlach, Tilman; Spengler, Ulrich; Buggisch, Peter; Neumann, Konrad; Sarrazin, Christoph; Zeuzem, Stefan; Berg, Thomas

2013-01-01

Complete suppression of viral replication is crucial in chronic HCV treatment in order to prevent relapse and resistance development. We wanted to find out which factors influence the period from being already HCV RNA negative by bDNA assay (< 615 IU/mL) to become undetectable by the more sensitive TMA test (< 5.3 IU/mL). Evaluated were 433 HCV type 1-infected patients. All of them received 1.5 ug/kg Peg-IFNα-2b plus ribavirin for 18-48 weeks. bDNA was performed weekly during the first 8 weeks and thereafter at weeks 12, 24, and 48. Patients who became bDNA undetectable were additionally analysed by TMA. Of the 309 patients with on-treatment response (< 615 IU/mL), 289 also reached undetectable HCV RNA levels by TMA. Multivariate analysis revealed that viremia ≤ 400,000 IU/mL (p = 0.001), fast initial virologic decline (p = 0.004) and absence of fibrosis (p = 0.035) were independent predictors of an accelerated on-treatment response by TMA assay in already bDNA negative patients. bDNA negative patients becoming HCV RNA undetectable by TMA within the following 3 weeks had a frequency of relapse of 21%, whereas those showing TMA negativity after 3 weeks relapsed in 38% (p = 0.001). In RVR patients (bDNA < 615 IU/mL at week 4) the corresponding relapse rates were 15.3% vs. 37.5%, respectively (p = 0.003). Early viral kinetics, baseline viremia and fibrosis stage are important tools to predict persistent minimal viremia during interferon-based therapy. The data have implications for designing a more refined treatment strategy in HCV infection, even in the setting of protease inhibitor-based triple treatment.

The value of FDG PET/CT for follow-up of patients with melanoma: a retrospective analysis

PubMed Central

Vensby, Philip H; Schmidt, Grethe; Kjær, Andreas; Fischer, Barbara M

2017-01-01

The incidence of melanoma (MM) is among the fastest rising cancers in the western countries. Positron Emission Tomography with Computed Tomography (PET/CT) is a valuable non-invasive tool for the diagnosis and staging of patients with MM. However, research on the value of PET/CT in follow-up of melanoma patients is limited. This study assesses the diagnostic value of PET/CT for follow-up after melanoma surgery. This retrospective study includes patients with MM who performed at least one PET/CT scan after initial surgery and staging. PET/CT findings were compared to histology, MRI or fine needle aspiration (FNA) to estimate the diagnostic accuracy. The diagnostic performance of PET/CT performed in patients with and without a clinical suspicion of relapse was compared. 238 patients (526 scans) were included. Of the 526 scans 130 (25%) scans were PET-positive, 365 (69%) PET-negative, and 28 (5%) had equivocal findings. Sensitivity was 89% [0.82-0.94], specificity 92% [0.89-0.95], positive and negative predictive values of 78% [0.70-0.84] and 97% [0.94-0.98] respectively. When stratified for reason of referral there was no statistical significant difference in the diagnostic accuracy of PET/CT between patients referred with or without a clinical suspicion of relapse. This study demonstrates that PET/CT despite a moderate sensitivity has a high negative predictive value in the follow-up of melanoma patients. Thus, a negative PET/CT-scan essentially rules out relapse. However, the frequency of false positive findings is relatively high, especially among patients undergoing a “routine” PET/CT with no clinical suspicion of relapse, potentially causing anxiety and leading to further diagnostic procedures. PMID:29348980

The value of FDG PET/CT for follow-up of patients with melanoma: a retrospective analysis.

PubMed

Vensby, Philip H; Schmidt, Grethe; Kjær, Andreas; Fischer, Barbara M

2017-01-01

The incidence of melanoma (MM) is among the fastest rising cancers in the western countries. Positron Emission Tomography with Computed Tomography (PET/CT) is a valuable non-invasive tool for the diagnosis and staging of patients with MM. However, research on the value of PET/CT in follow-up of melanoma patients is limited. This study assesses the diagnostic value of PET/CT for follow-up after melanoma surgery. This retrospective study includes patients with MM who performed at least one PET/CT scan after initial surgery and staging. PET/CT findings were compared to histology, MRI or fine needle aspiration (FNA) to estimate the diagnostic accuracy. The diagnostic performance of PET/CT performed in patients with and without a clinical suspicion of relapse was compared. 238 patients (526 scans) were included. Of the 526 scans 130 (25%) scans were PET-positive, 365 (69%) PET-negative, and 28 (5%) had equivocal findings. Sensitivity was 89% [0.82-0.94], specificity 92% [0.89-0.95], positive and negative predictive values of 78% [0.70-0.84] and 97% [0.94-0.98] respectively. When stratified for reason of referral there was no statistical significant difference in the diagnostic accuracy of PET/CT between patients referred with or without a clinical suspicion of relapse. This study demonstrates that PET/CT despite a moderate sensitivity has a high negative predictive value in the follow-up of melanoma patients. Thus, a negative PET/CT-scan essentially rules out relapse. However, the frequency of false positive findings is relatively high, especially among patients undergoing a "routine" PET/CT with no clinical suspicion of relapse, potentially causing anxiety and leading to further diagnostic procedures.

Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twu, C.-W.; Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung; Wang, W.-Y.

Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsedmore » patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.« less

Association of peripheral inflammation with body mass index and depressive relapse in bipolar disorder.

PubMed

Bond, David J; Andreazza, Ana C; Hughes, John; Dhanoa, Taj; Torres, Ivan J; Kozicky, Jan-Marie; Young, L Trevor; Lam, Raymond W; Yatham, Lakshmi N

2016-03-01

Bipolar I disorder (BD) is associated with increased inflammation, which is believed to be central to disease etiology and progression. However, BD patients also have high rates of obesity, itself an inflammatory condition, and the relative contributions of mood illness and obesity to inflammation are unknown. Moreover, the impact of inflammation on clinical illness course has not been well studied. The objectives of this analysis were therefore: (1) to determine if inflammation in BD is mood illness-related or secondary to elevated body mass index (BMI), and (2) to investigate the impact of inflammation on prospectively-ascertained relapse into depression and mania. We measured the serum levels of 7 inflammatory cytokines (TNF-α, γ-interferon, monocyte chemoattractant protein-1 [MCP-1], IL-1α, IL-2, IL-6, and IL-8) and 2 anti-inflammatory cytokines (IL-4 and IL-10) in 52 early-stage BD patients and 22 healthy subjects. In patients, a multivariate multiple regression model that controlled for psychotropic medications found that higher BMI, but not recent (past-6-month) mood episodes, predicted greater inflammatory cytokines (p=.05). Healthy subjects also had a BMI-related increase in inflammatory cytokines (p<.01), but it was counter-balanced by a compensatory increase in anti-inflammatory cytokines (p=.02), reducing their total inflammatory burden from higher BMI. In patients, linear regression showed that two inflammatory cytokines predicted depressive relapse in the 12 months after cytokine measurement: IL-1α (p<.01) and MCP-1 (p<.01). These results suggest that elevated BMI is a significant contributor to inflammation in BD, more so even than recent mood illness severity. They also point to inflammation as an important predictor of illness course, particularly depressive relapse. Copyright © 2015 Elsevier Ltd. All rights reserved.

Provocative Endoscopy to Identify Bleeding Site in Upper Gastrointestinal Bleeding: A Novel Approach in Transarterial Embolization.

PubMed

Kamo, Minobu; Fuwa, Sokun; Fukuda, Katsuyuki; Fujita, Yoshiyuki; Kurihara, Yasuyuki

2016-07-01

This report describes a novel approach to endoscopically induce bleeding by removing a clot from the bleeding site during angiography for upper gastrointestinal (UGI) hemorrhage. This procedure enabled accurate identification of the bleeding site, allowing for successful targeted embolization despite a negative initial angiogram. Provocative endoscopy may be a feasible and useful option for angiography of obscure bleeding sites in patients with UGI arterial hemorrhage. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Cognitive and affective trait and state factors influencing the long-term symptom course in remitted depressed patients.

PubMed

Timm, Christina; Ubl, Bettina; Zamoscik, Vera; Ebner-Priemer, Ulrich; Reinhard, Iris; Huffziger, Silke; Kirsch, Peter; Kuehner, Christine

2017-01-01

Major depressive disorder (MDD) is characterized by a high risk for relapses and chronic developments. Clinical characteristics such as residual symptoms have been shown to negatively affect the long-term course of MDD. However, it is unclear so far how trait repetitive negative thinking (RNT) as well as cognitive and affective momentary states, the latter experienced during daily-life, affect the long-term course of MDD. We followed up 57 remitted depressed (rMDD) individuals six (T2) and 36 (T3) months after baseline. Clinical outcomes were time to relapse, time spent with significant symptoms as a marker of chronicity, and levels of depressive symptoms at T2 and T3. Predictors assessed at baseline included residual symptoms and trait RNT. Furthermore, momentary daily life affect and momentary rumination, and their variation over the day were assessed at baseline using ambulatory assessment (AA). In multiple models, residual symptoms and instability of daily-life affect at baseline independently predicted a faster time to relapse, while chronicity was significantly predicted by trait RNT. Multilevel models revealed that depressive symptom levels during follow-up were predicted by baseline residual symptom levels and by instability of daily-life rumination. Both instability features were linked to a higher number of anamnestic MDD episodes. Our findings indicate that trait RNT, but also affective and cognitive processes during daily life impact the longer-term course of MDD. Future longitudinal research on the role of respective AA-phenotypes as potential transdiagnostic course-modifiers is warranted.

Detailed spectral profile analysis of electrocorticograms during freezing against penicillin-induced epileptiform discharges in the anesthetized rat.

PubMed

Tokiwa, Tatsuji; Zimin, Lev; Inoue, Takao; Nomura, Sadahiro; Suzuki, Michiyasu; Yamakawa, Takeshi

2018-07-01

Cryosurgery is an alternative technique for minimally invasive treatment of lesions. We have recently examined cryosurgery for epilepsy in animal models, and found that penicillin G (PG)-induced epileptiform discharges (EDs) mostly vanished after freezing. However, EDs were provoked again after insufficient freezing. Inadequate freezing is not visually detectable during and just after freezing and is not predictable beforehand. To manage this problem, we examined whether intraoperative monitoring of electrocorticograms (ECoGs) can predict recurrence of EDs after cryosurgery. A palm-sized cryoprobe system was applied to focal seizures in a Wistar rat model in which EDs were induced in advance by intracerebral injection of PG. During stable induction of EDs, the cryoprobe was carefully inserted into the epileptic region and this region was immediately frozen. After the series of prefreezing, freezing, and postfreezing, rats in which PG-induced EDs relapsed within 3 h were defined as the ED-relapsed (EDR) group, and other rats were defined as the ED-vanished (EDV) group. Time-frequency analysis was conducted on the ECoGs in each group through each freezing series. Relapse of PG-induced EDs on ECoG after the freezing series was associated with the remaining power of the delta band in the freezing period more strongly in the EDR group than in the EDV group. Success or failure of the freezing procedure can be predicted by the specificity of the delta band of the ECoG obtained intraoperatively. Copyright © 2018 Elsevier B.V. All rights reserved.

Smoking cessation treatment and outcomes patterns simulation: a new framework for evaluating the potential health and economic impact of smoking cessation interventions.

PubMed

Getsios, Denis; Marton, Jenő P; Revankar, Nikhil; Ward, Alexandra J; Willke, Richard J; Rublee, Dale; Ishak, K Jack; Xenakis, James G

2013-09-01

Most existing models of smoking cessation treatments have considered a single quit attempt when modelling long-term outcomes. To develop a model to simulate smokers over their lifetimes accounting for multiple quit attempts and relapses which will allow for prediction of the long-term health and economic impact of smoking cessation strategies. A discrete event simulation (DES) that models individuals' life course of smoking behaviours, attempts to quit, and the cumulative impact on health and economic outcomes was developed. Each individual is assigned one of the available strategies used to support each quit attempt; the outcome of each attempt, time to relapses if abstinence is achieved, and time between quit attempts is tracked. Based on each individual's smoking or abstinence patterns, the risk of developing diseases associated with smoking (chronic obstructive pulmonary disease, lung cancer, myocardial infarction and stroke) is determined and the corresponding costs, changes to mortality, and quality of life assigned. Direct costs are assessed from the perspective of a comprehensive US healthcare payer ($US, 2012 values). Quit attempt strategies that can be evaluated in the current simulation include unassisted quit attempts, brief counselling, behavioural modification therapy, nicotine replacement therapy, bupropion, and varenicline, with the selection of strategies and time between quit attempts based on equations derived from survey data. Equations predicting the success of quit attempts as well as the short-term probability of relapse were derived from five varenicline clinical trials. Concordance between the five trials and predictions from the simulation on abstinence at 12 months was high, indicating that the equations predicting success and relapse in the first year following a quit attempt were reliable. Predictions allowing for only a single quit attempt versus unrestricted attempts demonstrate important differences, with the single quit attempt simulation predicting 19 % more smoking-related diseases and 10 % higher costs associated with smoking-related diseases. Differences are most prominent in predictions of the time that individuals abstain from smoking: 13.2 years on average over a lifetime allowing for multiple quit attempts, versus only 1.2 years with single quit attempts. Differences in abstinence time estimates become substantial only 5 years into the simulation. In the multiple quit attempt simulations, younger individuals survived longer, yet had lower lifetime smoking-related disease and total costs, while the opposite was true for those with high levels of nicotine dependence. By allowing for multiple quit attempts over the course of individuals' lives, the simulation can provide more reliable estimates on the health and economic impact of interventions designed to increase abstinence from smoking. Furthermore, the individual nature of the simulation allows for evaluation of outcomes in populations with different baseline profiles. DES provides a framework for comprehensive and appropriate predictions when applied to smoking cessation over smoker lifetimes.

Stratification of medulloblastoma on the basis of histopathological grading.

PubMed

Giangaspero, Felice; Wellek, Stefan; Masuoka, Jun; Gessi, Marco; Kleihues, Paul; Ohgaki, Hiroko

2006-07-01

Medulloblastoma (WHO grade IV) is an embryonal tumour of the cerebellum and the most common malignant central nervous system tumour in children. Despite significant advances in treatment, 5-year survival rates are still less than 70%, suggesting the presence of subgroups with different response to radio/chemotherapy. In the present study, we re-evaluated a series of 347 medulloblastomas from the SIOP II clinical trial of the International Society of Paediatric Oncology to identify features predictive of clinical outcome. Relapse free survival for medulloblastomas with severe anaplasia [5-year rate: S(60)=49.5%], was significantly shorter than for tumours with moderate or mild anaplasia S(60)=65.4%; P=0.001). The difference between both groups was even larger when the presence or absence of extensive apoptosis was included (46.5 vs. 66.7%; P=0.0216). Other histological features including nodularity, necrosis, vascular proliferation and the presence of beta-catenin mutations (7% of cases) were not predictive for relapse free survival. These findings indicate that degree of anaplasia is the most significant histologic feature predictive of the survival of medulloblastoma patients.

Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy.

PubMed

Guillevin, R; Menuel, C; Taillibert, S; Capelle, L; Costalat, R; Abud, L; Habas, C; De Marco, G; Hoang-Xuan, K; Chiras, J; Vallée, J-N

2011-06-07

This study was designed to evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ). This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and (1)H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results. A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔV(n)/V(o)), according to a linear regression (P<0.001) in the 'response/no relapse' patient group, and with the evolution of the mean tumour volume (meanV(n)), according to an exponential regression (P<0.001) in the 'response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)(n)/(Cho/Cr)(o)), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)(n)-(Cho/Cr)(n))/(Cho/NAA)(n), at n=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (P=0.004). The (1)H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, (1)H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ.

Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy

PubMed Central

Guillevin, R; Menuel, C; Taillibert, S; Capelle, L; Costalat, R; Abud, L; Habas, C; De Marco, G; Hoang-Xuan, K; Chiras, J; Vallée, J-N

2011-01-01

Background: This study was designed to evaluate proton magnetic resonance spectroscopy (1H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ). Methods: This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and 1H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results. Results: A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)n and mean(Cho/NAA)n, were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)n and mean(Cho/NAA)n, were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔVn/Vo), according to a linear regression (P<0.001) in the ‘response/no relapse' patient group, and with the evolution of the mean tumour volume (meanVn), according to an exponential regression (P<0.001) in the ‘response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)n/(Cho/Cr)o), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)n−(Cho/Cr)n)/(Cho/NAA)n, at n=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (P=0.004). Conclusions: The 1H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, 1H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ. PMID:21610707

Long-term outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) enrolled in two prospective trials.

PubMed

Samson, Maxime; Puéchal, Xavier; Devilliers, Hervé; Ribi, Camillo; Cohen, Pascal; Stern, Marc; Pagnoux, Christian; Mouthon, Luc; Guillevin, Loïc

2013-06-01

The purpose of this study was to assess the outcomes of 118 patients with eosinophilic granulomatosis with polyangiitis (EGPA) enrolled in 2 prospective, randomized, open-label clinical trials (1994-2005), with or without Five-Factor Score (FFS)-defined poor-prognosis factors, focusing on survival, disease-free survival, relapses, clinical and laboratory findings, therapeutic responses, and factors predictive of relapse. Forty-four patients with FFS ≥ 1 were assigned to receive 6 or 12 cyclophosphamide pulses plus corticosteroids and the seventy-four with FFS = 0 received corticosteroids alone, with immunosuppressant adjunction when corticosteroids failed. Patients were followed (2005-2011) under routine clinical care in an extended study and data were recorded prospectively. Mean ± SD follow-up was 81.3 ± 39.6 months. Among the 118 patients studied, 29% achieved long-term remission and 10% died. Among the 115 patients achieving a first remission, 41% experienced ≥1 relapses, 26.1 ± 26.8 months after treatment onset, with 57% of relapses occurring when corticosteroid-tapering reached <10 mg/day. Treatment achieved new remissions in >90%, but relapses recurred in 38%. Overall survival was good, reaching 90% at 7 years, regardless of baseline severity. Age ≥65 years was the only factor associated with a higher risk of death during follow-up. The risk of relapse was higher for patients with anti-myeloperoxidase antibodies and lower for those with >3000 eosinophils/mm(3). Sequelae remained frequent, usually chronic asthma and peripheral neuropathy. In conclusion, EGPA patients' survival rate is very good when treatment is stratified according to the baseline FFS. Relapses are frequent, especially in patients with anti-myeloperoxidase antibodies and baseline eosinophilia <3000/mm(3). Copyright © 2013 Elsevier Ltd. All rights reserved.

The Second Antithyroid Drug Treatment Is Effective in Relapsed Graves' Disease Patients: A Median 11-Year Follow-Up Study.

PubMed

Kim, Ye An; Cho, Sun Wook; Choi, Hoon Sung; Moon, Shinje; Moon, Jae Hoon; Kim, Kyung Won; Park, Do Joon; Yi, Ka Hee; Park, Young Joo; Cho, Bo Youn

2017-04-01

Antithyroid drug (ATD) is a widely used treatment for Graves' disease (GD). However, its long-term efficiency remains unclear. This study investigated the long-term disease prognosis and predictive factors for relapse in ATD-treated GD patients. Newly diagnosed, ATD-treated GD patients with at least four years of follow-up were recruited (n = 187). Remission was defined as maintaining a euthyroid status for more than one year after ATD withdrawal. During 11.1 years (range 4.0-23.7 years) of median follow-up, overall, 51.9% of the newly diagnosed ATD-treated GD patients achieved remission, 32.1% continued ATD treatment, and 13.4% underwent other ablation treatments. The 10-year remission rates were higher in the first (34.2%) and second (25.5%) ATD courses than in any of the other subsequent ATD courses, and decreased as ATD treatments were repeated. The 10-year relapse rate was the highest after the third ATD treatment (71.4%) compared with that after the first (60.5%) and second (58.3%) courses. Longer duration of ATD treatment (odds ratio [OR] = 1.4 [confidence interval (CI) 1.2-1.7], p < 0.001), higher number of relapses (OR = 4.7 [CI 2.3-9.8], p < 0.001), and moderate to severe Graves' ophthalmopathy (OR = 4.1 [CI 1.1-15.2], p = 0.032) were associated with persistent disease status. A second course of ATD can be considered for GD patients after the first relapse because the chance of remission and the relapse rate are similar to the one after the first ATD treatment course. For GD patients with more than two relapses, or with an ATD treatment duration of more than four to five years, low-dose maintenance of ATD or ablative treatment needs to be considered.

The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

PubMed

Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

2015-01-01

Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for treatment of RRMS are predicted to be partially offset by reduced costs of relapses in the Canadian healthcare system.

Depression and eating disorders: treatment and course.

PubMed

Mischoulon, David; Eddy, Kamryn T; Keshaviah, Aparna; Dinescu, Diana; Ross, Stephanie L; Kass, Andrea E; Franko, Debra L; Herzog, David B

2011-05-01

We examined the course of major depressive disorder (MDD) and predictors of MDD recovery and relapse in a longitudinal sample of women with eating disorders (ED). 246 Boston-area women with DSM-IV anorexia nervosa-restricting (ANR; n=51), AN-binge/purge (ANBP; n=85), and bulimia nervosa (BN; n=110) were recruited between 1987 and 1991 and interviewed using the Eating Disorders Longitudinal Interval Follow-up Evaluation (LIFE-EAT-II) every 6-12 months for up to 12 years. 100 participants had MDD at study intake and 45 developed MDD during the study. Psychological functioning and treatment were assessed. Times to MDD onset (1 week-4.3 years), recovery (8 weeks-8.7 years), and relapse (1 week-5.2 years) varied. 70% recovered from MDD, but 65% subsequently relapsed. ANR patients were significantly less likely to recover from MDD than ANBP patients (p=0.029). Better psychological functioning and history of MDD were associated with higher chance of MDD recovery. Higher baseline depressive severity and full recovery from ED were associated with greater likelihood of MDD relapse; increased weight loss was somewhat protective. Adequate antidepressant treatment was given to 72% of patients with MDD and generally continued after MDD recovery. Time on antidepressants did not predict MDD recovery (p=0.27) or relapse (p=0.26). Small ED diagnostic subgroups; lack of non-ED control group. The course of MDD in EDs is protracted; MDD recovery may depend on ED type. Antidepressants did not impact likelihood of MDD recovery, nor protect against relapse, which may impact on treatment strategies for comorbid MDD and EDs. Copyright © 2010 Elsevier B.V. All rights reserved.

Psychometric properties of the Persian version of the Time to Relapse Questionnaire (TRQ) in substance use disorder.

PubMed

Khazaee-Pool, Maryam; Moridi, Minoo; Ponnet, Koen; Turner, Nigel; Pashaei, Tahereh

2016-11-01

Predicting time to relapse provides an opportunity for the development of relapse prevention interventions in drug users. The aim of the present study was to describe the development of the Persian version of the 9-item Time to Relapse Questionnaire (TRQ) and to evaluate its psychometric properties in an Iranian sample of treatment-seeking individuals with substance dependence (n = 150). The forward-backward method was used to translate the TRQ scale from English into Persian. After linguistic validation and a pilot check, a cross-sectional study was performed, and psychometric properties of the Iranian version of the questionnaire were assessed. The reliability was evaluated by Cronbach's alpha and test-retest analyses. In addition, the factor structure of the scale was extracted by applying confirmatory factor analysis. The mean age of participants was 40.52 (SD = 11.30) years. The mean scores for the content validity index (CVI) and the content validity ratio (CVR) were 0.93 and 0.81, respectively. A confirmatory factor analysis (CFA) demonstrated that the three-factor model of the TRQ was a good fit for the data and thus replicated the factor structure of the original English language TRQ. Cronbach's alpha presented good internal consistency (alpha = 0.76), and test-retest reliability of the TRQ instrument with 2-week intervals was appropriate (ICC = 0.84). The findings demonstrate that the Persian version of the TRQ is a reliable and valid scale for measuring time to relapse in Iranian drug users. The TRQ can be applied at the start of treatment so that clinical interventions can be targeted toward the different relapse styles.

MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle.

PubMed

Yang, I-Ping; Tsai, Hsiang-Lin; Hou, Ming-Feng; Chen, Ku-Chung; Tsai, Pei-Chien; Huang, Szu-Wei; Chou, Wen-Wen; Wang, Jaw-Yuan; Juo, Suh-Hang Hank

2012-08-01

Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

Surface electromyography of myopotential oversensing provoked by simultaneous straining and leftward twisting in a patient with an implantable cardioverter defibrillator.

PubMed

Ajiro, Yoichi; Shiga, Tsuyoshi; Shoda, Morio; Hagiwara, Nobuhisa

2017-03-01

An important step in diagnosing myopotential oversensing is to confirm its reproducibility using specific provocation maneuvers. Although most maneuvers involve the co-contraction of many muscles, no attempt has been made to assess relevant muscle activities by electromyography. We describe a case with an implantable cardioverter defibrillator (ICD) whose myopotential oversensing was provoked by simultaneous straining and leftward twisting. Simultaneous recordings from real-time ICD telemetry and myopotentials of the rectus abdominis, oblique abdominis, and diaphragm on electromyography during the provocation maneuvers were conducted. It was shown that all three muscles contracted simultaneously during the provocation maneuvers; the diaphragm activity was the main source of noise oversensing, and the twist itself caused oversensing possibly due to the change in the position of the lead. In conclusion, the electromyographic assessment of relevant muscle activities may be useful in assessing each muscle's role and its contribution to myopotential oversensing, especially in a patient whose myopotential oversensing requires complex maneuvers to be provoked.

Overview of the pharmacological spasm provocation test: Comparisons between acetylcholine and ergonovine.

PubMed

Sueda, Shozo; Kohno, Hiroaki; Ochi, Takaaki; Uraoka, Tadao; Tsunemitsu, Kensuke

2017-01-01

The spasm provocation tests of ergonovine and acetylcholine have been employed in the cardiac catheterization laboratory. Ergonovine acts through the serotogenic receptors, while acetylcholine acts through the muscarinic cholinergic receptors. Different mediators may have the potential to cause different coronary responses. However, there are few reports concerning the coronary response between ergonovine and acetylcholine in the same patients. Acetylcholine is supersensitive for females; spasm provoked by ergonovine is focal and proximal, whereas provoked spasm by acetylcholine is diffuse and distal. We should use both tests as supplementary in the clinic because ergonovine and acetylcholine have self-limitations to induce coronary spasms during daily life. The maximal pharmacological doses, administration methods, and the angiographical positive definition are remarkably different for each institution in the world. We recommend the pharmacological spasm provocation tests as Class I in the guidelines in patients with vasospastic angina throughout the world. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Philosophical Provocation: The Lifeblood of Clinical Ethics.

PubMed

McCullough, Laurence B

2017-02-01

The daily work of the clinical ethics teacher and clinical ethics consultant falls into the routine of classifying clinical cases by ethical type and proposing ethically justified alternatives for the professionally responsible management of a specific type of case. Settling too far into this routine creates the risk of philosophical inertia, which is not good either for the clinical ethicist or for the field of clinical ethics. The antidote to this philosophical inertia and resultant blinkered vision of clinical ethics is sustained, willing exposure to philosophical provocation. The papers in this clinical ethics issue of the Journal of Medicine and Philosophy provide just such philosophical provocation related to core topics in clinical ethics: the distinction between clinical practice and clinical research; telemedicine, or medicine at a distance; illness narratives; the concept of the placebo effect; and sex reassignment. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental panic provocation in healthy man—a translational role in anti-panic drug development?

PubMed Central

Kellner, Michael

2011-01-01

Experimental neurochemical provocation of panic attacks in susceptible human subjects has considerably expanded our knowledge of the pathophysiology and psychopharmacology of panic disorder. Some panicogens also elicit short-lived panic-like states in healthy man. This offers the opportunity to assess the anti-panic action of drugs in proof-of-concept studies. However, from current data it is still unclear whether experimental panic in healthy man is a valid translational model. Most such studies in healthy volunteers have been performed using a cholecystokinin tetrapeptide (CCK-4) challenge. While CCK-4 panic was blocked by alprazolam pretreatment, escitalopram showed negative results in healthy man. Preliminary findings on novel investigational drugs and a few problematic results will be reviewed. Small sample sizes in many panic provocation studies, lack of dose-response aspects, and still-insufficient knowledge about the biological underpinning of experimental and spontaneous panic limit the interpretation of existing findings and should inspire further research. PMID:22275853

Monoamine Oxidase A (MAOA) Genotype Predicts Greater Aggression Through Impulsive Reactivity to Negative Affect

PubMed Central

Chester, David S.; DeWall, C. Nathan; Derefinko, Karen J.; Estus, Steven; Peters, Jessica R.; Lynam, Donald R.; Jiang, Yang

2015-01-01

Low functioning MAOA genotypes have been reliably linked to increased reactive aggression, yet the psychological mechanisms of this effect remain largely unknown. The low functioning MAOA genotype’s established link to diminished inhibition and greater reactivity to conditions of negative affect suggest that negative urgency, the tendency to act impulsively in the context of negative affect, may fill this mediating role. Such MAOA carriers may have higher negative urgency, which may in turn predict greater aggressive responses to provocation. To test these hypotheses, 277 female and male participants were genotyped for an MAOA SNP yet to be linked to aggression (rs1465108), and then reported their negative urgency and past aggressive behavior. We replicated the effect of the low functioning MAOA genotype on heightened aggression, which was mediated by greater negative urgency. These results suggest that disrupted serotonergic systems predispose individuals towards aggressive behavior by increasing impulsive reactivity to negative affect. PMID:25637908

Networks of phobic fear: Functional connectivity shifts in two subtypes of specific phobia.

PubMed

Stefanescu, Maria R; Endres, Ralph J; Hilbert, Kevin; Wittchen, Hans-Ulrich; Lueken, Ulrike

2018-01-01

Anxiety disorders can be conceptualized by an abnormal interplay of emotion-processing brain circuits; however, knowledge of brain connectivity measures in specific phobia is still limited. To explore functional interactions within selected fear-circuitry structures (anterior cingulate cortex (ACC), amygdala, insula), we re-examined three task-based fMRI studies using a symptom provocation approach (n=94 subjects in total) on two different phobia subtypes (animal subtype as represented by snake phobia (SP) and blood-injection-injury subtype as represented by dental phobia (DP)), and a non-phobic healthy control group (HC). Functional connectivity (FC) analyses detected a negative coupling between the amygdala and the ACC in HC for both classes of phobic stimuli, while SP and DP lacked this inhibitory relationship during visual stimulus presentation. However, a negative FC between the insula and the amygdala was observed in DP during visual symptom provocation, which reversed to a positive FC under auditory symptom provocation pointing to effects depending on stimulus modality in DP. SP showed significantly higher FC towards snake-anxiety eliciting stimuli than HC on an average measure of FC, while DP showed a similar pattern under auditory stimulation only. These findings altogether indicate FC shifts during symptom provocation in specific phobia possibly reflecting impaired emotion regulation processes within fear-circuitry networks. FC hence could represent a prime target for neuroscience-informed augmentation strategies when treating pathological forms of fear. Copyright © 2017 Elsevier B.V. All rights reserved.

Trait aggressiveness modulates neurophysiological correlates of laboratory-induced reactive aggression in humans.

PubMed

Krämer, Ulrike M; Büttner, Sarah; Roth, Gerhard; Münte, Thomas F

2008-08-01

Reactive aggression following provocation is a frequent form of human social behavior. The neural basis of reactive aggression, especially its control, remains poorly understood, however. We conducted an event-related potential (ERP) study using a competitive reaction time task that elicits aggression through provocation. Participants were selected from a larger sample because of extreme scores in trait aggressiveness, yielding high and low trait aggressive groups. As each trial in the task is separated into a decision phase, during which the punishment level for the opponent is set, and an outcome phase, during which the punishment is applied or received, we were able to disentangle provocation-related and evaluation-related modulations of the ERPs during the aggressive interaction. Specifically, we observed an enhanced frontal negativity during the decision phase under high provocation that was positively correlated with the participants' ability to refrain from retaliation. This held true for high trait aggressive participants only, pointing to a higher need for inhibitory and control processes in these people when provoked. During the outcome phase, we detected a mediofrontal negativity in loss compared to win trials, resembling previous ERP findings to negative feedback stimuli, which have been linked to the evaluation of an outcome's valence. This mediofrontal negativity was differentially pronounced in aggressive and nonaggressive participants: Nonaggressive participants showed only a slightly smaller mediofrontal negativity in win than in loss trials, suggesting that for them punishing the opponent had a similar negative valence as being punished.

Inhaled Mannitol as a Laryngeal and Bronchial Provocation Test.

PubMed

Tay, Tunn Ren; Hoy, Ryan; Richards, Amanda L; Paddle, Paul; Hew, Mark

2017-03-01

Timely diagnosis of vocal cord dysfunction (VCD), more recently termed "inducible laryngeal obstruction," is important because VCD is often misdiagnosed as asthma, resulting in delayed diagnosis and inappropriate treatment. Visualization of paradoxical vocal cord movement on laryngoscopy is the gold standard for diagnosis, but is limited by poor test sensitivity. Provocation tests may improve the diagnosis of VCD, but the diagnostic performance of current tests is less than ideal. Alternative provocation tests are required. This pilot study demonstrates the feasibility of using inhaled mannitol for concurrent investigation of laryngeal and bronchial hyperresponsiveness. Consecutive patients with suspected VCD seen at our institution's asthma clinic underwent flexible laryngoscopy at baseline and following mannitol challenge. VCD was diagnosed on laryngoscopy based on inspiratory adduction, or >50% expiratory adduction of the vocal cords. Bronchial hyperresponsiveness after mannitol challenge was also assessed. We evaluated the interrater agreement of postmannitol laryngoscopy between respiratory specialists and laryngologists. Fourteen patients with suspected VCD in the context of asthma evaluation were included in the study. Mannitol provocation demonstrated VCD in three of the seven patients with normal baseline laryngoscopy (42.9%). Only two patients had bronchial hyperresponsiveness. There was substantial interrater agreement between respiratory specialists and laryngologists, kappa = 0.696 (95% confidence interval: 0.324-1) (P = 0.006). Inhaled mannitol can be used to induce VCD. It is well tolerated and can evaluate laryngeal and bronchial hyperresponsiveness at the same setting. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Eucapnic voluntary hyperventilation in diagnosing exercise-induced laryngeal obstructions.

PubMed

Christensen, Pernille M; Rasmussen, Niels

2013-11-01

Exercise-induced laryngeal obstructions (EILOs) cause exercise-related respiratory symptoms (ERRS) and are important differential diagnoses to exercise-induced asthma. The diagnostic method for EILOs includes provocation to induce the obstruction followed by a verification of the obstruction and the degree thereof. The objective of the present study was to examine if a eucapnic voluntary hyperventilation (EVH) test could induce laryngeal obstructions laryngoscopically identical in subtypes and development as seen during an exercise test. EVH and exercise testing with continuous laryngoscopy were performed during a screening of two national athletic teams (n = 67). The laryngoscopic recordings were examined for usability, abnormalities and maximal supraglottic and glottic obstruction using two currently available methods (Eilomea and CLE-score). The participants were asked questions on ERRS, and whether the symptoms experienced during each provocation matched those experienced during regular training. A total of 39 completed both tests. There were no significant differences in subtypes and development thereof, the experience of symptoms, and specificity and sensitivity between the methods. Significantly more recordings obtained during the exercise test were usable for evaluation primarily due to resilient mucus on the tip of the fiber-laryngoscope in the EVH test. Only recordings of six athletes from both provocation methods were usable for evaluation using the Eilomea method (high-quality demand). Amongst these, a linear correlation was found for the glottic obstruction. EVH tests can induce EILOs. However, the present test protocol needs adjustments to secure better visualisation of the larynx during provocation.

Collectivism and individualism in Latino recovery homes.

PubMed

Jason, Leonard A; Luna, Roberto D; Alvarez, Josefina; Stevens, Ed

2016-04-26

Research indicates that Latinos underutilize substance abuse interventions; cultural variables may contribute to difficulties accessing and completing treatment for this group. As a result, there is a need to understand the role of cultural constructs in treatment outcomes. The purpose of this study was to investigate how levels of collectivism (COL) and individualism (IND) relate to length of stay and relapse outcomes in self-run recovery homes. We compared Latinos in several culturally modified recovery Oxford Houses to Latinos in traditional recovery Oxford Houses. By examining COL and IND in the OH model, we explored whether aspects of COL and IND led to longer lengths of stay and better substance use outcomes. We hypothesized that higher levels of COL would predict longer stays in an Oxford House and less relapse. COL did not have a main effect on length of stay. However, COL had a significant interaction effect with house type such that COL was positively correlated with length of stay in traditional houses and negatively correlated with length of stay in the culturally modified condition; that is, those with higher collectivism tended to stay longer in traditional houses. When we investigated COL, length of stay, and substance use, COL was negatively correlated with relapse in the culturally modified houses and positively correlated with relapse in the traditional houses. In other words, those with higher COL spent less time and had less relapse in the culturally modified compared to the traditional Oxford Houses. The implications of these findings are discussed.

TEL/AML1 positivity in childhood ALL: average or better prognosis? Czech Paediatric Haematology Working Group.

PubMed

Zuna, J; Hrusák, O; Kalinová, M; Muzíková, K; Starý, J; Trka, J

1999-01-01

The presence of TEL/AML1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) defines a subgroup of patients with better than average outcome. However, the prognostic significance of this aberration has recently been disputed by the Berlin-Frankfurt-Münster (BFM) study group due to its relatively high incidence found in relapsed patients (19.6% and 21.9%, in two cohorts). In contrast, only four out of 45 (8.9%) unselected relapsed patients (all of whom had been treated according to BFM protocols) in the Czech Republic carry this fusion. From March 1995 to June 1998, 41 out of 190 (21.6%) newly diagnosed children with ALL were TEL/AML1-positive. There is a statistically significant difference between the incidence of TEL/AML1 fusion at diagnosis and at relapse within our group (P = 0.035). Interim analysis of the minimal residual disease (MRD) detection shows heterogeneity within the group of newly diagnosed TEL/AML1-positive leukaemias--10 out of 24 patients tested at the end of induction therapy had detectable levels of MRD. However, only one of these patients reached relapse-predictive level (10(-3)) of MRD. In conclusion, we corroborate low frequency of TEL/AML1 positivity among relapsed patients with ALL among Czech children who are treated by the BFM protocols. Moreover, we demonstrate different patterns of bone marrow clean-up in TEL/AML1-positive patients.

Genomic analysis of adult B-ALL identifies potential markers of shorter survival.

PubMed

Patel, Shiven; Mason, Clinton C; Glenn, Martha J; Paxton, Christian N; South, Sara T; Cessna, Melissa H; Asch, Julie; Cobain, Erin F; Bixby, Dale L; Smith, Lauren B; Reshmi, Shalini; Gastier-Foster, Julie M; Schiffman, Joshua D; Miles, Rodney R

2017-05-01

B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA). As B-cell developmental genes play a crucial role in this leukemia, we assessed such for recurrent deletions in diagnostic and relapse samples. We confirmed previous findings that the most prevalent deletions of these genes occur in CDKN2A, IKZF1, and PAX5, with several others at lower frequencies. Of the 16 samples having paired diagnostic and relapse samples, 5 showed new deletions in these recurrent B-cell related genes and 8 showed abolishment. Deletion of EBF1 heralded a significant negative prognostic impact on relapse free survival in univariate and multivariate analyses. The combination of both a CDKN2A/B deletion and an IKZF1 alteration (26% of cases) also showed a trend toward predicting worse overall survival compared to having only one or neither of these deletions. These findings add to the understanding of genomic influences on this comparably understudied disease cohort that upon further validation may help identify patients who would benefit from upfront treatment intensification. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rates and predictors of relapse after natural and treated remission from alcohol use disorders

PubMed Central

Moos, Rudolf H.; Moos, Bernice S.

2007-01-01

Aims This study examined the rates and predictors of 3-year remission, and subsequent 16-year relapse, among initially untreated individuals with alcohol use disorders who did not obtain help or who participated in treatment and/or Alcoholics Anonymous in the first year after recognizing their need for help. Design and measures A sample of individuals (n = 461) who initiated help-seeking was surveyed at baseline and 1 year, 3 years, 8 years and 16 years later. Participants provided information on their life history of drinking, alcohol-related functioning and life context and coping. Findings Compared to individuals who obtained help, those who did not were less likely to achieve 3-year remission and subsequently were more likely to relapse. Less alcohol consumption and fewer drinking problems, more self-efficacy and less reliance on avoidance coping at baseline predicted 3-year remission; this was especially true of individuals who remitted without help. Among individuals who were remitted at 3 years, those who consumed more alcohol but were less likely to see their drinking as a significant problem, had less self-efficacy, and relied more on avoidance coping, were more likely to relapse by 16 years. These findings held for individuals who initially obtained help and for those who did not. Conclusions Natural remission may be followed by a high likelihood of relapse; thus, preventive interventions may be indicated to forestall future alcohol problems among individuals who cut down temporarily on drinking on their own. PMID:16445550

Fluorodeoxyglucose Uptake on Positron Emission Tomography Is a Useful Predictor of Long-Term Pain Control After Palliative Radiation Therapy in Patients With Painful Bone Metastases: Results of a Single-Institute Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tahara, Takatoshi, E-mail: taka.t-may7@med.Tottori-u.ac.jp; Fujii, Shinya; Ogawa, Toshihide

Purpose: To determine whether fluorodeoxyglucose positron emission tomography (FDG-PET) before and after palliative radiation therapy (RT) can predict long-term pain control in patients with painful bone metastases. Methods and Materials: Thirty-one patients with bone metastases who received RT were prospectively included. Forty painful metastatic treatment fields were evaluated. All patients had undergone pre-RT and post-RT PET/CT scanning. We evaluated the relationships between the pre-RT, post-RT, and changes in maximum standardized uptake value (SUV{sub max}) and the pain response, and between SUV{sub max} and pain relapse of the bone metastases in the treatment field. In addition, we compared the SUV{sub max}more » according to the length of time from the completion of RT to pain relapse of the bone metastases. Results: Regarding the pain response at 4 weeks after the completion of RT, there were 36 lesions of 27 patients in the responder group and 4 lesions of 4 patients in the nonresponder group. Changes in the SUV{sub max} differed significantly between the responder and nonresponder groups in both the early and delayed phases (P=.0292 and P=.0139, respectively), but no relationship was observed between the pre-RT and post-RT SUV{sub max} relative to the pain response. The responder group was evaluated for the rate of relapse. Thirty-five lesions of 26 patients in the responder group were evaluated, because 1 patient died of acute renal failure at 2 months after RT. Twelve lesions (34%) showed pain relapse, and 23 lesions (66%) did not. There were significant differences between the relapse and nonrelapse patients in terms of the pre-RT (early/delayed phases: P<.0001/P<.0001), post-RT (P=.0199/P=.0261), and changes in SUV{sub max} (P=.0004/P=.004). Conclusions: FDG-PET may help predict the outcome of pain control in the treatment field after palliative RT for painful bone metastases.« less

Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moran, Meena S., E-mail: meena.moran@yale.edu; Yang Qifeng; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, People's Republic of China

2011-12-01

Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpressionmore » of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin-negative patients (86% vs. 100%, p = .029) on univariate analysis, but it did not retain its significance on multivariate analysis (hazard ratio, 2.52; 95% confidence interval, 0.804-7.920, p = .113). No other subgroups were identified in which a correlation was found between VEGF expression and local relapse. Conclusion: To our knowledge, our study is the first to assess the prognostic value of VEGF with the endpoint of local relapse in early-stage breast cancer treated with BCT, an important question given the recent increased use of targeted antiangiogenic agents in early-stage breast cancer. Our study results suggest that VEGF is not an independent predictor of local RFS after BCT, but additional, larger studies specifically analyzing the endpoint of VEGF and local relapse are warranted.« less

Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves' disease.

PubMed

Kim, Kyung Won; Park, Young Joo; Kim, Tae Yong; Park, Do Joon; Park, Kyong Soo; Cho, Bo Youn

2007-12-01

In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

Membrane expression of MRP-1, but not MRP-1 splicing or Pgp expression, predicts survival in patients with ESFT.

PubMed

Roundhill, E; Burchill, S

2013-07-09

Primary Ewing's sarcoma family of tumours (ESFTs) may respond to chemotherapy, although many patients experience subsequent disease recurrence and relapse. The survival of ESFT cells following chemotherapy has been attributed to the development of resistant disease, possibly through the expression of ABC transporter proteins. MRP-1 and Pgp mRNA and protein expression in primary ESFTs was determined by quantitative reverse-transcriptase PCR (RT-qPCR) and immunohistochemistry, respectively, and alternative splicing of MRP-1 by RT-PCR. We observed MRP-1 protein expression in 92% (43 out of 47) of primary ESFTs, and cell membrane MRP-1 was highly predictive of both overall survival (P<0.0001) and event-free survival (P<0.0001). Alternative splicing of MRP-1 was detected in primary ESFTs, although the pattern of splicing variants was not predictive of patient outcome, with the exception of loss of exon 9 in six patients, which predicted relapse (P=0.041). Pgp protein was detected in 6% (38 out of 44) of primary ESFTs and was not associated with patient survival. For the first time we have established that cell membrane expression of MRP-1 or loss of exon 9 is predictive of outcome but not the number of splicing events or expression of Pgp, and both may be valuable factors for the stratification of patients for more intensive therapy.

Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study.

PubMed

Van Den Neste, E; Schmitz, N; Mounier, N; Gill, D; Linch, D; Trneny, M; Milpied, N; Radford, J; Ketterer, N; Shpilberg, O; Dührsen, U; Ma, D; Brière, J; Thieblemont, C; Salles, G; Moskowitz, C H; Glass, B; Gisselbrecht, C

2016-01-01

Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.

Abnormally high expression of POLD1, MCM2, and PLK4 promotes relapse of acute lymphoblastic leukemia.

PubMed

Li, Sheng; Wang, Chengzhong; Wang, Weikai; Liu, Weidong; Zhang, Guiqin

2018-05-01

This study aimed to explore the underlying mechanism of relapsed acute lymphoblastic leukemia (ALL).Datasets of GSE28460 and GSE18497 were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between diagnostic and relapsed ALL samples were identified using Limma package in R, and a Venn diagram was drawn. Next, functional enrichment analyses of co-regulated DEGs were performed. Based on the String database, protein-protein interaction network and module analyses were also conducted. Moreover, transcription factors and miRNAs targeting co-regulated DEGs were predicted using the WebGestalt online tool.A total of 71 co-regulated DEGs were identified, including 56 co-upregulated genes and 15 co-downregulated genes. Functional enrichment analyses showed that upregulated DEGs were significantly enriched in the cell cycle, and DNA replication, and repair related pathways. POLD1, MCM2, and PLK4 were hub proteins in both protein-protein interaction network and module, and might be potential targets of E2F. Additionally, POLD1 and MCM2 were found to be regulated by miR-520H via E2F1.High expression of POLD1, MCM2, and PLK4 might play positive roles in the recurrence of ALL, and could serve as potential therapeutic targets for the treatment of relapsed ALL.

Rituximab in refractory myasthenia gravis: extended prospective study results.

PubMed

Beecher, Grayson; Anderson, Dustin; Siddiqi, Zaeem A

2018-05-09

Rituximab appears beneficial in treatment-refractory myasthenia gravis (MG), however, prospective, long-term durability data is lacking. In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 AChR, 9 MuSK, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B cell counts were serially monitored. At mean follow-up of 28.8 ± 19.0 months (range=6-66 months), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (p<0.0001). Mean prednisone dose declined from 25.2 ± 15.1 mg/d to 7.3 ± 7.1 mg/d (p=0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range=9-23 months). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B cell depletion (range=24-45 months) after one cycle. Sustained clinical improvement was associated with rituximab after one cycle, with prolonged time to relapse and reduction in steroid dose. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial.

PubMed

Chen, Ray Y; Via, Laura E; Dodd, Lori E; Walzl, Gerhard; Malherbe, Stephanus T; Loxton, André G; Dawson, Rodney; Wilkinson, Robert J; Thienemann, Friedrich; Tameris, Michele; Hatherill, Mark; Diacon, Andreas H; Liu, Xin; Xing, Jin; Jin, Xiaowei; Ma, Zhenya; Pan, Shouguo; Zhang, Guolong; Gao, Qian; Jiang, Qi; Zhu, Hong; Liang, Lili; Duan, Hongfei; Song, Taeksun; Alland, David; Tartakovsky, Michael; Rosenthal, Alex; Whalen, Christopher; Duvenhage, Michael; Cai, Ying; Goldfeder, Lisa C; Arora, Kriti; Smith, Bronwyn; Winter, Jill; Barry Iii, Clifton E

2017-11-06

Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment. Methods : This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C. Discussion : Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. NCT02821832.

Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial.

PubMed

Fei, F; Messina, C; Slaets, L; Chakiba, C; Cameron, D; Bogaerts, J; Bonnefoi, H

2015-02-01

Although achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some patients still relapse. The objectives of this study were to describe the types of events in this group of patients and to identify predictive factors for relapse. Patients with large operable or locally advanced breast cancers (T4d tumours were excluded) were randomised to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel followed by three cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in the primary tumour and axillary lymph nodes at surgery. Two Cox regression analyses were performed to identify predictive factors of relapse: one for recurrence-free interval (RFI) and one for distant recurrence-free interval (DRFI). Out of 283 eligible patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6% (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors for RFI after pCR were identified. For DRFI, tumour size was the only predictor: Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR, 2.80 (95% CI, 0.62-12.64) p=0.0048. In this study, clinical tumour size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours having an increased risk for distant recurrence compared to T1-2 tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

PubMed Central

Chen, Ray Y.; Via, Laura E.; Dodd, Lori E.; Walzl, Gerhard; Malherbe, Stephanus T.; Loxton, André G.; Dawson, Rodney; Wilkinson, Robert J.; Thienemann, Friedrich; Tameris, Michele; Hatherill, Mark; Diacon, Andreas H.; Liu, Xin; Xing, Jin; Jin, Xiaowei; Ma, Zhenya; Pan, Shouguo; Zhang, Guolong; Gao, Qian; Jiang, Qi; Zhu, Hong; Liang, Lili; Duan, Hongfei; Song, Taeksun; Alland, David; Tartakovsky, Michael; Rosenthal, Alex; Whalen, Christopher; Duvenhage, Michael; Cai, Ying; Goldfeder, Lisa C.; Arora, Kriti; Smith, Bronwyn; Winter, Jill; Barry III, Clifton E.

2017-01-01

Background: By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment. Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C. Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. Trial Registration: NCT02821832 PMID:29528048

Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation

PubMed Central

Koenecke, Christian; Göhring, Gudrun; de Wreede, Liesbeth C.; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Jürgen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kröger, Nicolaus

2015-01-01

The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification. PMID:25552702

Accurate prediction of cardiorespiratory fitness using cycle ergometry in minimally disabled persons with relapsing-remitting multiple sclerosis.

PubMed

Motl, Robert W; Fernhall, Bo

2012-03-01

To examine the accuracy of predicting peak oxygen consumption (VO(2peak)) primarily from peak work rate (WR(peak)) recorded during a maximal, incremental exercise test on a cycle ergometer among persons with relapsing-remitting multiple sclerosis (RRMS) who had minimal disability. Cross-sectional study. Clinical research laboratory. Women with RRMS (n=32) and sex-, age-, height-, and weight-matched healthy controls (n=16) completed an incremental exercise test on a cycle ergometer to volitional termination. Not applicable. Measured and predicted VO(2peak) and WR(peak). There were strong, statistically significant associations between measured and predicted VO(2peak) in the overall sample (R(2)=.89, standard error of the estimate=127.4 mL/min) and subsamples with (R(2)=.89, standard error of the estimate=131.3 mL/min) and without (R(2)=.85, standard error of the estimate=126.8 mL/min) multiple sclerosis (MS) based on the linear regression analyses. Based on the 95% confidence limits for worst-case errors, the equation predicted VO(2peak) within 10% of its true value in 95 of every 100 subjects with MS. Peak VO(2) can be accurately predicted in persons with RRMS who have minimal disability as it is in controls by using established equations and WR(peak) recorded from a maximal, incremental exercise test on a cycle ergometer. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Uncertainty in the Bayesian meta-analysis of normally distributed surrogate endpoints.

PubMed

Bujkiewicz, Sylwia; Thompson, John R; Spata, Enti; Abrams, Keith R

2017-10-01

We investigate the effect of the choice of parameterisation of meta-analytic models and related uncertainty on the validation of surrogate endpoints. Different meta-analytical approaches take into account different levels of uncertainty which may impact on the accuracy of the predictions of treatment effect on the target outcome from the treatment effect on a surrogate endpoint obtained from these models. A range of Bayesian as well as frequentist meta-analytical methods are implemented using illustrative examples in relapsing-remitting multiple sclerosis, where the treatment effect on disability worsening is the primary outcome of interest in healthcare evaluation, while the effect on relapse rate is considered as a potential surrogate to the effect on disability progression, and in gastric cancer, where the disease-free survival has been shown to be a good surrogate endpoint to the overall survival. Sensitivity analysis was carried out to assess the impact of distributional assumptions on the predictions. Also, sensitivity to modelling assumptions and performance of the models were investigated by simulation. Although different methods can predict mean true outcome almost equally well, inclusion of uncertainty around all relevant parameters of the model may lead to less certain and hence more conservative predictions. When investigating endpoints as candidate surrogate outcomes, a careful choice of the meta-analytical approach has to be made. Models underestimating the uncertainty of available evidence may lead to overoptimistic predictions which can then have an effect on decisions made based on such predictions.

Pathobiologic Markers of the Ewing Sarcoma Family of Tumors: State of the Art and Prediction of Behaviour

PubMed Central

Pinto, Alfredo; Dickman, Paul; Parham, David

2011-01-01

Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development. PMID:20981347

Experimentally Assessed Reactive Aggression in Borderline Personality Disorder

PubMed Central

Kogan-Goloborodko, Olga; Brügmann, Elisabeth; Repple, Jonathan; Habel, Ute; Clemens, Benjamin

2016-01-01

Approximately 73% of patients suffering from Borderline personality disorder (BPD) exhibit aggressive behaviour, which severely hinders therapeutic work and clinical improvement. Because the underlying mechanisms of aggression in BPD are not yet completely understood, additional research in this domain has a high clinical and scientific relevance. We employed a modified version of the Taylor Aggression Paradigm (mTAP), in order to examine for the first time whether this task can be used to differentiate between BPD patients and healthy controls with regard to reactive aggression. In the mTAP, the amount of money subtracted by a virtual opponent was categorized into ‘low’ (10–20 cents) and ‘high’ (80–100 cents) provocations, enabling us to compare how much money BPD patients and healthy controls subtracted (i.e., how aggressively participants responded) following high and low provocation trials. Our results showed that, compared to healthy controls, BPD patients showed higher overall aggression, higher aggression after high provocation trials, as well as a larger difference between high and low provocation trials. This finding was corroborated by a neuropsychological assessment, demonstrating higher levels of aggression and impulsivity in BPD patients. Interestingly, reactive aggression in the mTAP was positively correlated with symptom severity and impulsivity in BPD patients. We suggest that the mTAP provides a valuable tool allowing psychiatrists to quantify reactive aggression in BPD. Therefore, clinicians and researchers might consider this task, as a short experimental measure of reactive aggression, either in future studies or to aid diagnostic assessment during clinical practice. PMID:27851804

Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease.

PubMed

Yamamoto, Toshihide

2015-09-01

Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-μg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses ≤15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI.

A commercially available immunoglobulin E-based test for food allergy gives inconsistent results in healthy ponies.

PubMed

Dupont, S; De Spiegeleer, A; Liu, D J X; Lefère, L; van Doorn, D A; Hesta, M

2016-01-01

Commercial immunoglobulin E (IgE)-based tests are available for diagnosis of food allergies and are commonly used in equine practice. However, these tests have been proven unreliable as a screening method in man and other species, but not critically evaluated in equids. Therefore, a commercially available IgE-based test for horses was evaluated. To evaluate the consistency of the results obtained with a commercially available IgE-based test for food allergy diagnosis in ponies (Phase I) and to subject ponies to a provocation trial with the presumed allergens (Phase II). Allergen screening followed by experimental food provocation trials in healthy ponies. Blood samples of 17 healthy Shetland ponies were taken at 2 different time points, sent blinded to a commercial laboratory for screening of common food allergens and the results were evaluated for consistency (Phase I). Ponies that were positive for food allergens were consecutively challenged orally with each allergen separately for 14 days (Phase II). A washout period of one week was applied in ponies with multiple positive results. Clinical parameters and serum amyloid A were monitored during the provocation trial. Only 7/17 ponies were negative on the IgE-based test at the 2 time points, 3 had positive results twice but only one tested positive twice for the same food allergen. No abnormalities were noted during the provocation trials. This study demonstrated that this IgE-based test is not a reliable screening tool for food allergy in healthy equids. © 2015 EVJ Ltd.

Difference Between Dormant Conduction Sites Revealed by Adenosine Triphosphate Provocation and Unipolar Pace-Capture Sites Along the Ablation Line After Pulmonary Vein Isolation.

PubMed

Kogawa, Rikitake; Okumura, Yasuo; Watanabe, Ichiro; Sonoda, Kazumasa; Sasaki, Naoko; Takahashi, Keiko; Iso, Kazuki; Nagashima, Koichi; Ohkubo, Kimie; Nakai, Toshiko; Kunimoto, Satoshi; Hirayama, Atsushi

2016-01-01

Dormant pulmonary vein (PV) conduction revealed by adenosine/adenosine triphosphate (ATP) provocation test and exit block to the left atrium by pacing from the PV side of the ablation line ("pace and ablate" method) are used to ensure durable pulmonary vein isolation (PVI). However, the mechanistic relation between ATP-provoked PV reconnection and the unexcitable gap along the ablation line is unclear.Forty-five patients with atrial fibrillation (AF) (paroxysmal: 31 patients, persistent: 14 patients; age: 61.1 ± 9.7 years) underwent extensive encircling PVI (EEPVI, 179 PVs). After completion of EEPVI, an ATP provocation test (30 mg, bolus injection) and unipolar pacing (output, 10 mA; pulse width, 2 ms) were performed along the previous EEPVI ablation line to identify excitable gaps. Dormant conduction was revealed in 29 (34 sites) of 179 PVs (16.2%) after EEP-VI (22/45 patients). Pace capture was revealed in 59 (89 sites) of 179 PVs (33.0%) after EEPVI (39/45 patients), and overlapping sites, ie, sites showing both dormant conduction and pace capture, were observed in 22 of 179 (12.3%) PVs (17/45 patients).Some of the ATP-provoked dormant PV reconnection sites were identical to the sites with excitable gaps revealed by pace capture, but most of the PV sites were differently distributed, suggesting that the main underling mechanism differs between these two forms of reconnection. These findings also suggest that performance of the ATP provocation test followed by the "pace and ablate" method can reduce the occurrence of chronic PV reconnections.

Correlation of clinical examination characteristics with three sources of chronic low back pain.

PubMed

Young, Sharon; Aprill, Charles; Laslett, Mark

2003-01-01

Research has demonstrated some progress in using a clinical examination to predict discogenic or sacroiliac (SI) joint sources of pain. No clear predictors of symptomatic lumbar zygapophysial joints have yet been demonstrated. To identify significant components of a clinical examination that are associated with symptomatic lumbar discs, zygapophysial joints and SI joints. A prospective, criterion-related concurrent validity study performed at a private radiology practice specializing in spinal diagnostics. The sample consisted of 81 patients with chronic lumbopelvic pain referred for diagnostic injections. Contingency tables were constructed for nine features of the clinical evaluation compared with the results of diagnostic injections. Statistical analysis included chi-squared test for independence, phi and odds ratios with confidence intervals. Patients received blinded clinical examinations by physical therapists, and diagnostic injections were used as the criterion standard. Significant relationships were found between discogenic pain and centralization of pain during repeated movement testing, and pain when rising from sitting. Lumbar zygapophysial joint pain was associated with absence of pain when rising from sitting. Sacroiliac joint pain was related to three or more positive pain provocation tests, pain when rising from sitting, unilateral pain and absence of lumbar pain. Significant correlations exist between clinical examination findings and symptomatic lumbar discs, zygapophysial and SI joints. The strongest relationships were seen between SI joint pain and three or more positive pain provocation tests, centralization of pain for symptomatic discs and absence of pain when rising from sitting for symptomatic lumbar zygapophysial joints.

The Oral Provocation Test for Raw Egg in Patients with Hen Egg Allergy.

PubMed

Kido, Jun; Nishi, Natsuko; Matsumoto, Tomoaki

2018-06-06

Many researchers have made efforts to develop diagnostic tools for predicting the outcome of oral food challenges (OFCs). The aim of this study was to assess the diagnostic value of the skin prick test (SPT) and blood-specific IgE concentrations based on the outcome of the OFCs for heated and raw hen egg. This study included 103 children with suspected hen egg allergy (HEA; median age 23 months, range 10-155; 72 boys, 31 girls). Forty-three patients were diagnosed with HEA by OFC. Of 60 patients who tolerated heated egg white (HEW), 22 underwent the OFC for raw hen egg and 7 developed adverse reactions after ingesting raw egg. Their wheal diameters and specific IgE levels for egg white and ovomucoid were determined. Wheal diameters as well as blood-specific IgE levels for egg white and ovomucoid were significantly larger in children with positive OFC results for HEW than in those with negative results. However, there were no significant differences between the positive and negative test results for raw hen egg white (REW) in wheal diameter or blood-specific IgE levels. The SPT and blood-specific IgE can be used to diagnose HEA. However, the provocation test for REW in children without HEW allergy is important because the values of SPT and specific IgE were not significantly different between children with and without raw egg allergy. © 2018 S. Karger AG, Basel.

Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

PubMed

Simonini, Gabriele; Bracaglia, Claudia; Cattalini, Marco; Taddio, Andrea; Brambilla, Alice; De Libero, Cinzia; Pires Marafon, Denise; Caputo, Roberto; Cimaz, Rolando

2017-06-01

To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. A retrospective, multicenter, cohort study. Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Change in self-esteem predicts depressive symptoms at follow-up after intensive multimodal psychotherapy for major depression.

PubMed

Dinger, Ulrike; Ehrenthal, Johannes C; Nikendei, Christoph; Schauenburg, Henning

2017-09-01

Reduced self-esteem is a core symptom of depression, but few studies have investigated within-treatment change of self-esteem as a predictor of long-term outcome in depression. This study investigated change in self-esteem during 8 weeks of multimodal, psychodynamically oriented psychotherapy for 40 depressed patients and tested whether it would predict outcome 6 months after termination. Data was drawn from a randomized clinical pilot trial on day-clinic versus inpatient psychotherapy for depression. Findings supported the association between change in self-esteem and follow-up depression severity, even when controlling for within-treatment symptom change. Change in self-esteem was not related to overall symptoms and interpersonal problems at follow-up. Thus, change in self-esteem may be an important variable in preventing relapse for depression. Self-esteem is related to depressive symptoms and interpersonal problems. Improvement of self-esteem during psychotherapy correlates with improvements of symptoms and interpersonal problems. Change of self-esteem during psychotherapy predicts depressive symptoms 6 months after termination of therapy. When treating depressed patients, psychotherapists should work towards an improvement of self-esteem in order to prevent relapse. Copyright © 2017 John Wiley & Sons, Ltd.

Reduced hematopoietic stem cell frequency predicts outcome in acute myeloid leukemia.

PubMed

Wang, Wenwen; Stiehl, Thomas; Raffel, Simon; Hoang, Van T; Hoffmann, Isabel; Poisa-Beiro, Laura; Saeed, Borhan R; Blume, Rachel; Manta, Linda; Eckstein, Volker; Bochtler, Tilmann; Wuchter, Patrick; Essers, Marieke; Jauch, Anna; Trumpp, Andreas; Marciniak-Czochra, Anna; Ho, Anthony D; Lutz, Christoph

2017-09-01

In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse. Copyright© 2017 Ferrata Storti Foundation.

Long-term results of pneumatic dilatation for relapsing symptoms of achalasia after Heller myotomy.

PubMed

Legros, Ludivine; Ropert, Alain; Brochard, Charlène; Bouguen, Guillaume; Pagenault, Maël; Siproudhis, Laurent; Bretagne, Jean-François

2014-09-01

The aim of this study was to assess the efficacy and safety of pneumatic dilatation (PD) to treat symptom recurrence after Heller myotomy (HM). Consecutive patients receiving PD for relapsing symptoms following prior HM were included in this retrospective single-center study. Eckardt score ≤3 and/or ∆ Eckardt (difference between Eckardt score before and after dilatation) ≥3 defined the success of initial dilatation. Patients who maintained response longer than 2 months after initial dilatation were defined as short-term responders. Relapsers were offered further on-demand dilatation. Remission was defined as an Eckardt score ≤3 at the study endpoint. Kaplan-Meier survival curves were used to determine relapse rates. Eighteen patients (11 women, seven men) were included from January 2004 to January 2013. Ten patients had type I achalasia, and seven had type III, according to the Chicago classification. Thirty-nine PDs were performed (1.5 [1-2.25] per patient). All patients had short-term responses. The remission rate at the endpoint, after a median follow-up of 33 months, was 78%, but 44% were treated with on-demand PD during the follow-up interval. The proportions of patients without relapse and subsequent PD were 72% at 12 months, 65% at 24 and 36 months, and 49% at 48 months. No factors predictive of long-term response, particularly the type of achalasia, could be identified in this series. There were no perforations. In treating symptom recurrence following HM, PD was safe and effective over the long term when combined with subsequent PD. © 2014 John Wiley & Sons Ltd.

Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia.

PubMed

Sutton, Rosemary; Shaw, Peter J; Venn, Nicola C; Law, Tamara; Dissanayake, Anuruddhika; Kilo, Tatjana; Haber, Michelle; Norris, Murray D; Fraser, Chris; Alvaro, Frank; Revesz, Tamas; Trahair, Toby N; Dalla-Pozza, Luciano; Marshall, Glenn M; O'Brien, Tracey A

2015-02-01

Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment-related mortality of 8%. Leukaemia-free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre-HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre-HSCT (LFS 41%, OS 64%, P < 0·0001) or post-HSCT (LFS 35%, OS 55%, P < 0·0001). Patients with B-other ALL had more relapses (CIR 50%, LFS 41%) than T-ALL and the main precursor-B subtypes including BCR-ABL1, KMT2A (MLL), ETV6-RUNX1 (TEL-AML1) and hyperdiploidy >50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy. © 2014 John Wiley & Sons Ltd.

Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse.

PubMed

Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K; Allen, Sharon; al'Absi, Mustafa

2015-09-01

Leptin has been linked to tobacco craving and withdrawal-related symptoms. Very few studies have examined leptin prospectively in both male and female nonsmokers and smokers. We examine leptin concentrations prospectively in both male and female nonsmokers and smokers to assess the associations of leptin with psychological symptoms and smoking relapse during ad libitum smoking, the first 48 h post quit, and 4 weeks post-cessation. Self-report psychological, anthropomorphic, and biological measures (cotinine, carbon monoxide, and plasma leptin) were collected before and after 48 h of smoking abstinence. Smokers were stratified at 28 days post quit as abstinent or relapsed if they had smoked daily for seven consecutive days at any point in the 28 days. Leptin concentration (square root transformed ng/ml) increased over the 48-h abstinence, but only in female abstainers. In contrast, leptin was very stable across time for nonsmokers, relapsers, and males. Cox regression supported that increased leptin was associated with decreased risk of relapse. Leptin was correlated negatively with withdrawal symptoms for abstainers only. Females produce more leptin than males and this level increases from ad libitum smoking to 48-h post quit. The current analysis indicates that a leptin increase early in cessation predicts abstinence. The increase in women, but not men, in response to abstinence provides further evidence of important gender differences. The negative correlation between leptin and withdrawal symptoms indicates a possible protective effect of leptin. Further research is ongoing to elucidate the psychological and biological determinants of this effect.

Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure.

PubMed

Oba, Masaru; Hasegawa, Kiyoshi; Matsuyama, Yutaka; Shindoh, Junichi; Mise, Yoshihiro; Aoki, Taku; Sakamoto, Yoshihiro; Sugawara, Yasuhiko; Makuuchi, Masatoshi; Kokudo, Norihiro

2014-06-01

Recurrence-free survival (RFS) may not be a surrogate for overall survival (OS) in patients with resectable colorectal liver metastases (CLM). We investigated whether a new composite tool-time to surgical failure (TSF)-is a suitable endpoint. The medical records of consecutive patients who underwent curative resection for CLM at our center over a 17-year period were reviewed. Patients with liver-limited tumors (n = 371) who had not received previous treatment for metastasis were eligible for analysis. TSF was defined as the time until unresectable relapse or death. The correlations between TSF and OS, and between RFS and OS, were assessed for all the eligible patients. The median OS, TSF, and RFS were 5.7, 2.7, and 0.7 years, respectively, and the 5-year OS, TSF, and RFS rates were 52.6, 39.8, and 23.7 %, respectively, for all patients. The rates of first, second, and third relapse were 75.5, 77.6, and 70.8 %, respectively, and repeat resections were performed in 54.3 % (first relapses), 40.7 % (second relapses), and 47.1 % (third relapses) of patients. The concordance proportions of TSF and RFS for OS events were 0.83 and 0.65, respectively. The correlation between TSF and OS was stronger than that between RFS and OS in terms of the predicted probabilities. The correlation between TSF and OS was stronger than that between RFS and OS after curative hepatic resection. TSF could be a suitable endpoint for CLM overall management.

Pacifists and Revenge-Seekers in Response to Unambiguous Peer Provocation.

PubMed

McDonald, Kristina L; Asher, Steven R

2018-01-19

In order to better understand why some children retaliate when they feel provoked and others do not, the present study identified "pacifistically-oriented" children who made negative interpretations in response to unambiguous provocations, yet did not endorse revenge goals, and compared them to "revenge-seeking" children who also made negative interpretations but did endorse revenge goals. Groups were identified based on seventh graders' (N = 367; 54.77% male; 22.89% racial/ethnic minority) responses to hypothetical situations in which a peer excluded and insulted them. Comparing these groups revealed that Pacifists endorsed relationship-maintaining goals and emotion regulation goals more highly than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs about negative reciprocity and aggression being legitimate more highly than Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were Pacifists, based on a measure of vigilance for signs of disrespect and expectations that others would disrespect them. Together these findings point to social-cognitive and emotion-related processes that may inhibit revenge-seeking in unambiguous provocation situations, even when children interpret the peer's behavior quite negatively.

Use of Provocative Angiography to Localize Site in Recurrent Gastrointestinal Bleeding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Ciaran, E-mail: ciaranjohnston@yahoo.co.uk; Tuite, David; Pritchard, Ruth

2007-09-15

Background. While the source of most cases of lower gastrointestinal bleeding may be diagnosed with modern radiological and endoscopic techniques, approximately 5% of patients remain who have negative endoscopic and radiological investigations.Clinical Problem. These patients require repeated hospital admissions and blood transfusions, and may proceed to exploratory laparotomy and intraoperative endoscopy. The personal and financial costs are significant. Method of Diagnosis and Decision Making. The technique of adding pharmacologic agents (anticoagulants, vasodilators, fibrinolytics) during standard angiographic protocols to induce a prohemorrhagic state is termed provocative angiography. It is best employed when significant bleeding would otherwise necessitate emergency surgery. Treatment. Thismore » practice frequently identifies a bleeding source (reported success rates range from 29 to 80%), which may then be treated at the same session. We report the case of a patient with chronic lower gastrointestinal hemorrhage with consistently negative endoscopic and radiological workup, who had an occult source of bleeding identified only after a provocative angiographic protocol was instituted, and who underwent succeeding therapeutic coil embolization of the bleeding vessel.« less

Assessment of Social Information Processing in early childhood: development and initial validation of the Schultz Test of Emotion Processing-Preliminary Version.

PubMed

Schultz, David; Ambike, Archana; Logie, Sean Kevin; Bohner, Katherine E; Stapleton, Laura M; Vanderwalde, Holly; Min, Christopher B; Betkowski, Jennifer A

2010-07-01

Crick and Dodge's (Psychological Bulletin 115:74-101, 1994) social information processing model has proven very useful in guiding research focused on aggressive and peer-rejected children's social-cognitive functioning. Its application to early childhood, however, has been much more limited. The present study responds to this gap by developing and validating a video-based assessment tool appropriate for early childhood, the Schultz Test of Emotion Processing-Preliminary Version (STEP-P). One hundred twenty-five Head Start preschool children participated in the study. More socially competent children more frequently attributed sadness to the victims of provocation and labeled aggressive behaviors as both morally unacceptable and less likely to lead to positive outcomes. More socially competent girls labeled others' emotions more accurately. More disruptive children more frequently produced physically aggressive solutions to social provocations, and more disruptive boys less frequently interpreted social provocations as accidental. The STEP-P holds promise as an assessment tool that assesses knowledge structures related to the SIP model in early childhood.

Reproducibility of manual pressure force on provocation of the sacroiliac joint.

PubMed

Levin, U; Nilsson-Wikmar, L; Stenström, C H; Lundeberg, T

1998-01-01

Previous studies of pain-provocation sacroiliac (SI) joint tests have revealed conflicting results. The aim of the present study was to evaluate the intra- and inter-test reliability of pressure force applied during distraction test, compression test and pressure on the apex sacralis. Seventeen physiotherapists (PTs), median age 43 years and median clinical experience 11 years, all experienced in musculoskeletal evaluation and therapy, participated in the study. Each PT performed each test on the same healthy volunteer for 20 s, on three separate occasions, at intervals of one week using a specially constructed examination table which registered pressure force. The PTs were capable of maintaining a relatively constant pressure force for 20 s. The intra-test reliability was acceptable even though there were individual differences on different occasions between those PTs who used the SI joint tests often and those who seldom or never used them. The inter-test reliability was insufficient. The findings indicate the advantage of registering pressure force as a complement for standardized methods for pain-provoking tests and when learning provocation tests, since individual variability was considerable.

May nasal hyperreactivity be a sequela of recurrent common cold?

PubMed

Cassano, M; Cassano, P; Ciprandi, G

2011-01-01

Respiratory viral infections may worsen bronchial hyperreactivity. However, there is no data on the possible role of recurrent infectious rhinitis in nose hyperreactivity. This study was therefore designed to investigate whether subjects suffering from recurrent common cold have nasal hyperreactivity, assessed by histamine nasal challenge. This study included a group of 40 patients (19 males, mean age 34.1 years) with history of at least five episodes of common cold in the previous year, but without documented allergy, and twenty healthy subjects (8 males, mean age 32.3 years) were enrolled as control group, all of whom were non-allergic. Nasal provocation test with histamine was performed in all subjects. Nasal provocation test with histamine induced a 200% increase in nasal resistance after provocation in 24 (60%) patients suffering from recurrent viral rhinitis. No normal subject had an increase >180% in nasal resistance. There was a significant difference between the patient group and the control group (p<0.05). In conclusion, this study shows that nasal hyperreactivity might be a sequela of recurrent common cold. Further studies should be conducted to confirm this preliminary finding.

Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization.

PubMed

Alvarez-Cuesta, E; Madrigal-Burgaleta, R; Angel-Pereira, D; Ureña-Tavera, A; Zamora-Verduga, M; Lopez-Gonzalez, P; Berges-Gimeno, M P

2015-07-01

Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). Prospective, observational, longitudinal study with patients who, during a 3-year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin-specific IgE was determined in oxaliplatin-reactive patients (who underwent DPT regardless of oxaliplatin-specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty-four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin-specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30-56% of patients, depending on culprit-drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin-specific IgE and oxaliplatin-ST in the largest series of oxaliplatin-reactive patients reported to date (74 oxaliplatin-reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cost-effectiveness model of long-acting risperidone in schizophrenia in the US.

PubMed

Edwards, Natalie C; Rupnow, Marcia F T; Pashos, Chris L; Botteman, Marc F; Diamond, Ronald J

2005-01-01

Schizophrenia is a devastating and costly illness that affects 1% of the population in the US. Effective pharmacological therapies are available but suboptimal patient adherence to either acute or long-term therapeutic regimens reduces their effectiveness. The availability of a long-acting injection (LAI) formulation of risperidone may increase adherence and improve clinical and economic outcomes for people with schizophrenia. To assess the cost effectiveness of risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI over a 1-year time period in outpatients with schizophrenia who had previously suffered a relapse requiring hospitalisation. US healthcare system. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were used to populate a decision-analysis model comparing the four treatment alternatives. The model captured: rates of patient compliance; rates, frequency and duration of relapse; incidence of adverse events (bodyweight gain and extrapyramidal effects); and healthcare resource utilisation and associated costs. Primary outcomes were: the proportion of patients with relapse; the frequency of relapse per patient; the number of relapse days per patient; and total direct medical cost per patient per year. Costs are in year 2002 US dollars. Based on model projections, the proportions of patients experiencing a relapse requiring hospitalisation after 1 year of treatment were 66% for haloperidol decanoate LAI, 41% for oral risperidone and oral olanzapine and 26% for risperidone LAI, while the proportion of patients with a relapse not requiring hospitalisation were 60%, 37%, 37% and 24%, respectively. The mean number of days of relapse requiring hospitalisation per patient per year was 28 for haloperidol decanoate LAI, 18 for oral risperidone and oral olanzapine and 11 for risperidone LAI, while the mean number of days of relapse not requiring hospitalisation was 8, 5, 5 and 3, respectively. This would translate into direct medical cost savings with risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI of USD 397, USD 1742, and USD 8328, respectively. These findings were supported by sensitivity analyses. The use of risperidone LAI for treatment of outpatients with schizophrenia is predicted in this model to result in better clinical outcomes and lower total healthcare costs over 1 year than its comparators, oral risperidone, oral olanzapine and haloperidol decanoate LAI. Risperidone LAI may therefore be a cost saving therapeutic option for outpatients with schizophrenia in the US healthcare setting.

Substance Abuse among High-Risk Sexual Offenders: Do Measures of Lifetime History of Substance Abuse Add to the Prediction of Recidivism over Actuarial Risk Assessment Instruments?

ERIC Educational Resources Information Center

Looman, Jan; Abracen, Jeffrey

2011-01-01

There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has…

Elaborations on sexual assault on dates among Israeli students: risk, detrimental effect, and resilience factors.

PubMed

Shechory Bitton, Mally; Ben-David, Sarah

2014-12-01

The current study of 668 Israeli male and female students examines the prevalence of gendered risk factors for sexual assault (SA) on dates, posttraumatic stress disorder (PTSD) as a detrimental effect of SA, and self-efficacy as resiliency to refuse unwanted sex following SA. Two different sets of risk factors that increased the likelihood of SA on dates emerged from the hierarchical regression. Sexual experience, use of drugs, and private location increased the risk of being SA victims among males, whereas sexual experience, perceived provocative behavior, and alcohol use increased the risk among females. In addition, PTSD and self-efficacy to refuse unwanted sex following SA on dates were predicted by the extent of coercive sexual victimization. PTSD was also predicted by subjective perception of sexual behavior and rape myths, whereas efficacy was predicted by private location. The findings contribute to the literature by showing the contribution of various risk factors to experiencing SA, and by showing SA effect on PTSD and self-efficacy. © The Author(s) 2013.

Unscrambling Egg Allergy: The Diagnostic Value of Specific IgE Concentrations and Skin Prick Tests for Ovomucoid and Egg White in the Management of Children with Hen's Egg Allergy.

PubMed

Marriage, D E; Erlewyn-Lajeunesse, M; Unsworth, D J; Henderson, A J

2012-01-01

Resolution of egg allergy occurs in the majority of egg allergic children. Positive specific IgE antibodies to ovomucoid (OVM) have been suggested to be of greater predictive value for persistent egg allergy than specific IgE to egg white. The performance of OVM-specific IgE antibody levels in a cohort of children referred for a routine egg challenge was compared with egg white specific IgE levels in predicting a positive egg challenge. 24/47 subjects had persistent egg allergy. Receiver operating characteristic analysis showed that OVM-specific IgE testing was the most useful test for the diagnosis of persistent egg allergy. The optimal decision points for the prediction of persistent egg allergy were >0.35 kUA/L for specific IgE levels to both EW and OVM, and ≥3 mm for SPT. Children with specific IgE levels suggestive of persistent egg allergy need not be subject to an egg provocation challenge, reducing both costs and risks to the child.

Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood.

PubMed

Hohmann, Christopher; Milles, Bianca; Schinke, Michael; Schroeter, Michael; Ulzheimer, Jochen; Kraft, Peter; Kleinschnitz, Christoph; Lehmann, Paul V; Kuerten, Stefanie

2014-09-16

B cells are attracting increasing attention in the pathogenesis of multiple sclerosis (MS). B cell-targeted therapies with monoclonal antibodies or plasmapheresis have been shown to be successful in a subset of patients. Here, patients with either relapsing-remitting (n = 24) or secondary progressive (n = 6) MS presenting with an acute clinical relapse were screened for their B cell reactivity to brain antigens and were re-tested three to nine months later. Enzyme-linked immunospot technique (ELISPOT) was used to identify brain-reactive B cells in peripheral blood mononuclear cells (PBMC) directly ex vivo and after 96 h of polyclonal stimulation. Clinical severity of symptoms was determined using the Expanded Disability Status Scale (EDSS). Nine patients displayed B cells in the blood producing brain-specific antibodies directly ex vivo. Six patients were classified as B cell positive donors only after polyclonal B cell stimulation. In 15 patients a B cell response to brain antigens was absent. Based on the autoreactive B cell response we categorized MS relapses into three different patterns. Patients who displayed brain-reactive B cell responses both directly ex vivo and after polyclonal stimulation (pattern I) were significantly younger than patients in whom only memory B cell responses were detectable or entirely absent (patterns II and III; p = 0.003). In one patient a conversion to a positive B cell response as measured directly ex vivo and subsequently also after polyclonal stimulation was associated with the development of a clinical relapse. The evaluation of the predictive value of a brain antigen-specific B cell response showed that seven of eight patients (87.5%) with a pattern I response encountered a clinical relapse during the observation period of 10 months, compared to two of five patients (40%) with a pattern II and three of 14 patients (21.4%) with a pattern III response (p = 0.0005; hazard ratio 6.08 (95% confidence interval 1.87-19.77). Our data indicate actively ongoing B cell-mediated immunity against brain antigens in a subset of MS patients that may be causative of clinical relapses and provide new diagnostic and therapeutic options for a subset of patients.

Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)

ClinicalTrials.gov

2017-12-04

Hematologic Cancer; Relapse Leukemia; Relapsed Adult ALL; Relapsed Adult AML; Relapsed CLL; Relapsed Non Hodgkin Lymphoma; Relapsed Hodgkin's Lymphoma; Relapsed Myelodysplastic Syndromes; Relapsed Multiple Myeloma

Anti-IgE Monoclonal Antibody (Omalizumab) in Refractory and Relapsing Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss): Data on Seventeen Patients.

PubMed

Jachiet, Marie; Samson, Maxime; Cottin, Vincent; Kahn, Jean-Emmanuel; Le Guenno, Guillaume; Bonniaud, Philippe; Devilliers, Hervé; Bouillet, Laurence; Gondouin, Anne; Makhlouf, Fatma; Meaux-Ruault, Nadine; Gil, Helder; Bienvenu, Boris; Coste, André; Groh, Matthieu; Giraud, Violaine; Dominique, Stéphane; Godeau, Bertrand; Puéchal, Xavier; Khouatra, Chahera; Ruivard, Marc; Le Jeunne, Claire; Mouthon, Luc; Guillevin, Loïc; Terrier, Benjamin

2016-09-01

To describe the efficacy and safety of omalizumab, an anti-IgE monoclonal antibody, in patients with refractory and/or relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). We conducted a nationwide retrospective study including EGPA patients who received omalizumab. Response was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of ≤7.5 mg/day (complete response) or >7.5 mg/day (partial response). Seventeen patients (median age 45 years) received omalizumab for severe steroid-dependent asthma (88%) and/or sinonasal involvement (18%). After a median follow-up of 22 months, 6 patients (35%) achieved a complete response, 5 patients (30%) achieved a partial response, and 6 patients (35%) had no improvement. The median Birmingham Vasculitis Activity Score decreased from 2.5 at baseline to 0.5 at 12 months. The median number of exacerbations per month decreased from 1 at baseline to 0 at 12 months, and the median forced expiratory volume in 1 second increased from 63% of the percent predicted at baseline to 85% of the percent predicted at 12 months. The median prednisone dosage decreased from 16 mg/day at baseline to 11 mg/day at 6 months and 9 mg/day at 12 months. Omalizumab was discontinued in 8 patients (47%) during follow-up, because of remission (12.5%), adverse event despite disease remission (12.5%), refractory disease (25%), or relapse (50%). Relapses included retrobulbar optic neuritis attributable to EGPA in 2 patients and severe asthma flare in 2 others. The results of this study suggest that omalizumab may have a corticosteroid-sparing effect in EGPA patients with asthmatic and/or sinonasal manifestations, but reducing the corticosteroid dose may also increase the risk of severe EGPA flares, which raises the question of the safety of omalizumab in patients with EGPA. © 2016, American College of Rheumatology.

Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors.

PubMed

Farnedi, Anna; Rossi, Silvia; Bertani, Nicoletta; Gulli, Mariolina; Silini, Enrico Maria; Mucignat, Maria Teresa; Poli, Tito; Sesenna, Enrico; Lanfranco, Davide; Montebugnoli, Lucio; Leonardi, Elisa; Marchetti, Claudio; Cocchi, Renato; Ambrosini-Spaltro, Andrea; Foschini, Maria Pia; Perris, Roberto

2015-05-03

Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors. A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups. HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival. An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.

Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation.

PubMed

Mannis, Gabriel N; Martin, Thomas G; Damon, Lloyd E; Andreadis, Charalambos; Olin, Rebecca L; Kong, Katherine A; Faham, Malek; Hwang, Jimmy; Ai, Weiyun Z; Gaensler, Karin M L; Sayre, Peter H; Wolf, Jeffrey L; Logan, Aaron C

2016-06-01

Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of ≥ 1 × 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD ≥1 × 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cue reactivity and its relation to craving and relapse in alcohol dependence: a combined laboratory and field study.

PubMed

Witteman, Jurriaan; Post, Hans; Tarvainen, Mika; de Bruijn, Avalon; Perna, Elizabeth De Sousa Fernandes; Ramaekers, Johannes G; Wiers, Reinout W

2015-10-01

The present study investigated the nature of physiological cue reactivity and craving in response to alcohol cues among alcohol-dependent patients (N = 80) who were enrolled in detoxification treatment. Further, the predictive value with regard to future drinking of both the magnitude of the physiological and craving response to alcohol cues while in treatment and the degree of alcohol-cue exposure in patients' natural environment was assessed. Physiological reactivity and craving in response to experimental exposure to alcohol and soft drink advertisements were measured during detoxification treatment using heart rate variability and subjective rating of craving. Following discharge, patients monitored exposure to alcohol advertisements for five consecutive weeks with a diary and were followed up with an assessment of relapse at 5 weeks and 3 months post-discharge. The results indicated that the presence of alcohol cues such as the portrayal of the drug and drinking behaviour induced physiological cue reactivity and craving. Additionally, cue reactivity and craving were positively correlated, and cue reactivity was larger for patients with shorter histories of alcohol dependence. Further, patients reported a substantial daily exposure to alcohol cues. The magnitude of cue reactivity and the craving response to alcohol cues at baseline and degree of exposure to alcohol cues in patients' natural environment did not predict relapse. It is concluded that the presence of alcohol cues such as portrayal of alcoholic beverages and drinking behaviour induces cue reactivity and craving in alcohol dependence through a conditioned appetitive response.

Tobacco Withdrawal Components and Their Relations with Cessation Success

PubMed Central

Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Sheffer, Megan A.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel M.; Kim, Su-Young; Kaye, Jesse T.; Hefner, Kathryn R.; Baker, Timothy B.

2011-01-01

Rationale Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. Objectives This research was intended to provide information about two core components of withdrawal (negative affect and craving): 1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and 2) how these dimensions relate to cessation outcome. Methods Adult smokers (N=1504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence. Results Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse. Conclusions Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions. PMID:21416234

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group.

PubMed

Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

2010-04-01

About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. The median overall survival after relapse was 4.5 months (95% CI, 4-5 months) with a 5-year overall survival of 10% (95% CI, 8%-12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%-30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%-53%) and a 5-year disease-free survival of 53% (95% CI, 34%-72%). The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group

PubMed Central

Oriol, Albert; Vives, Susana; Hernández-Rivas, Jesús-María; Tormo, Mar; Heras, Inmaculada; Rivas, Concepción; Bethencourt, Concepción; Moscardó, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-José; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

2010-01-01

Background About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. Design and Methods We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. Results The median overall survival after relapse was 4.5 months (95% CI, 4–5 months) with a 5-year overall survival of 10% (95% CI, 8%–12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%–30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%–53%) and a 5-year disease-free survival of 53% (95% CI, 34%–72%). Conclusions The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available. PMID:20145276

Impact of Social Cognition on Alcohol Dependence Treatment Outcome: Poorer Facial Emotion Recognition Predicts Relapse/Dropout.

PubMed

Rupp, Claudia I; Derntl, Birgit; Osthaus, Friederike; Kemmler, Georg; Fleischhacker, W Wolfgang

2017-12-01

Despite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion. Fifty-nine alcohol-dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, "dropout"). Compared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout. Social cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach. Copyright © 2017 by the Research Society on Alcoholism.

In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy.

PubMed

Bourhis, J; Wilson, G; Wibault, P; Bosq, J; Chavaudra, N; Janot, F; Luboinski, B; Eschwege, F; Malaise, E P

1993-08-01

Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required. To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables.

Membrane expression of MRP-1, but not MRP-1 splicing or Pgp expression, predicts survival in patients with ESFT

PubMed Central

Roundhill, E; Burchill, S

2013-01-01

Background: Primary Ewing's sarcoma family of tumours (ESFTs) may respond to chemotherapy, although many patients experience subsequent disease recurrence and relapse. The survival of ESFT cells following chemotherapy has been attributed to the development of resistant disease, possibly through the expression of ABC transporter proteins. Methods: MRP-1 and Pgp mRNA and protein expression in primary ESFTs was determined by quantitative reverse-transcriptase PCR (RT-qPCR) and immunohistochemistry, respectively, and alternative splicing of MRP-1 by RT-PCR. Results: We observed MRP-1 protein expression in 92% (43 out of 47) of primary ESFTs, and cell membrane MRP-1 was highly predictive of both overall survival (P<0.0001) and event-free survival (P<0.0001). Alternative splicing of MRP-1 was detected in primary ESFTs, although the pattern of splicing variants was not predictive of patient outcome, with the exception of loss of exon 9 in six patients, which predicted relapse (P=0.041). Pgp protein was detected in 6% (38 out of 44) of primary ESFTs and was not associated with patient survival. Conclusion: For the first time we have established that cell membrane expression of MRP-1 or loss of exon 9 is predictive of outcome but not the number of splicing events or expression of Pgp, and both may be valuable factors for the stratification of patients for more intensive therapy. PMID:23799853

Predicting Rapid Relapse Following Treatment for Chemical Dependence: A Matched-Subjects Design.

ERIC Educational Resources Information Center

Svanum, Soren; McAdoo, William George

1989-01-01

Persons who underwent residential treatment for chemical dependency were identified as three-month treatment failures (N=52) or successes (N=52). Subjects were matched on Minnesota Multiphasic Personality Inventory (MMPI) scores. Found posttreatment depression, anxiety, and sleep problems strongly related to failure among psychiatric MMPI group;…

Transgender Youth and Suicidal Behaviors: Applying the Interpersonal Psychological Theory of Suicide

PubMed Central

Grossman, Arnold H.; Park, Jung Yeon; Russell, Stephen T.

2016-01-01

The interpersonal psychological theory of suicide (IPTS) was used to examine suicidal thoughts and behaviors among 129 transgender and gender nonconforming (TGNC) youth. Youth were categorized according to their gender identities: female-to-male (FTM), male-to-female (MTF), female-to-different-gender (FTDG), and male-to-different gender (MTDG). Higher percentages of suicidal ideation were reported by FTDG and FTM youth; and higher percentages of suicide attempts by FTDG and MTDG youth. Perceived burdensomeness and thwarted belongingness were significantly related to suicidal ideation and/or suicide attempts. Experiences of painful, provocative and harmful events and acquired capability significantly predicted suicide attempts. The findings support IPTS in explaining suicidal behaviors among TGNC youth. Implications for prevention and intervention efforts are discussed. PMID:28344728

Transgender Youth and Suicidal Behaviors: Applying the Interpersonal Psychological Theory of Suicide.

PubMed

Grossman, Arnold H; Park, Jung Yeon; Russell, Stephen T

2016-01-01

The interpersonal psychological theory of suicide (IPTS) was used to examine suicidal thoughts and behaviors among 129 transgender and gender nonconforming (TGNC) youth. Youth were categorized according to their gender identities: female-to-male (FTM), male-to-female (MTF), female-to-different-gender (FTDG), and male-to-different gender (MTDG). Higher percentages of suicidal ideation were reported by FTDG and FTM youth; and higher percentages of suicide attempts by FTDG and MTDG youth. Perceived burdensomeness and thwarted belongingness were significantly related to suicidal ideation and/or suicide attempts. Experiences of painful, provocative and harmful events and acquired capability significantly predicted suicide attempts. The findings support IPTS in explaining suicidal behaviors among TGNC youth. Implications for prevention and intervention efforts are discussed.

Predictors of Aggressive Inflammatory Bowel Disease

PubMed Central

Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.

2011-01-01

Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958

Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: Relation to electromechanical delay.

PubMed

Badran, Hala Mahfouz; Ibrahim, Waleed Abdou; Faheem, Naglaa; Yassin, Rehab; Alashkar, Tamer; Yacoub, Magdi

2015-01-01

Left ventricular outflow tract obstruction (LVOT) is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). It is of major importance that the provocation modalities used are validated against each other. To define the magnitude of LVOT gradients provocation during both isosorbide dinitrate (ISDN) inhalation and treadmill exercise in non-obstructive HCM and analyze the correlation to the electromechanical delay using speckle tracking. We studied 39 HCM pts (64% males, mean age 38 ± 13 years) regional LV longitudinal strain and electromechanical delay (TTP) was analyzed at rest using speckle tracking. LVOT gradient was measured at rest and after ISDN then patients underwent a treadmill exercise echocardiography (EE) and LVOT gradient was measured at peak exercise. The maximum effect of ISDN on LVOT gradient was obtained at 5 minutes, it increased to a significant level in 12 (31%) patients, and in 14 (36%) patients using EE, with 85.6% sensitivity & 100% specificity. Patients with latent obstruction had larger left atrial volume and lower E/A ratio compared to the non-obstructive group (p < 0.01). LVOTG using ISDN was significantly correlated with that using EE (p < 0.0001), resting LVOTG (p < 0.0001), SAM (p < 0.0001), EF% (p < 0.02) and regional electromechanical delay but not related to global LV longitudinal strain. Using multivariate regression, resting LVOTG (p = 0.006) & TTP mid septum (p = 0.01) were found to be independent predictors of latent LVOT obstruction using ISDN. There is a comparable diagnostic value of nitrate inhalation to exercise testing in provocation of LVOT obstruction in HCM. Latent obstruction is predominantly dependent on regional electromechanical delay.

Provocation of left ventricular outflow tract obstruction using nitrate inhalation in hypertrophic cardiomyopathy: Relation to electromechanical delay

PubMed Central

Badran, Hala Mahfouz; Ibrahim, Waleed Abdou; Faheem, Naglaa; Yassin, Rehab; Alashkar, Tamer; Yacoub, Magdi

2015-01-01

Background: Left ventricular outflow tract obstruction (LVOT) is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). It is of major importance that the provocation modalities used are validated against each other. Aim: To define the magnitude of LVOT gradients provocation during both isosorbide dinitrate (ISDN) inhalation and treadmill exercise in non-obstructive HCM and analyze the correlation to the electromechanical delay using speckle tracking. Methods: We studied 39 HCM pts (64% males, mean age 38 ± 13 years) regional LV longitudinal strain and electromechanical delay (TTP) was analyzed at rest using speckle tracking. LVOT gradient was measured at rest and after ISDN then patients underwent a treadmill exercise echocardiography (EE) and LVOT gradient was measured at peak exercise. Results: The maximum effect of ISDN on LVOT gradient was obtained at 5 minutes, it increased to a significant level in 12 (31%) patients, and in 14 (36%) patients using EE, with 85.6% sensitivity & 100% specificity. Patients with latent obstruction had larger left atrial volume and lower E/A ratio compared to the non-obstructive group (p < 0.01). LVOTG using ISDN was significantly correlated with that using EE (p < 0.0001), resting LVOTG (p < 0.0001), SAM (p < 0.0001), EF% (p < 0.02) and regional electromechanical delay but not related to global LV longitudinal strain. Using multivariate regression, resting LVOTG (p = 0.006) & TTP mid septum (p = 0.01) were found to be independent predictors of latent LVOT obstruction using ISDN. Conclusion: There is a comparable diagnostic value of nitrate inhalation to exercise testing in provocation of LVOT obstruction in HCM. Latent obstruction is predominantly dependent on regional electromechanical delay. PMID:26779503

Psychophysical and vasomotor evidence for interdependency of TRPA1 and TRPV1 nociceptive responses in human skin: an experimental study.

PubMed

Nielsen, Thomas Arendt; Eriksen, Matilde Alida; Gazerani, Parisa; Andersen, Hjalte Holm

2018-05-25

The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and inter-relationship in humans is therefore crucial. Preclinical results are contradictory concerning co-expression and functional interdependency of TRPV1 and TRPA1 but no human evidence exists. This human experimental study investigated whether functional responses from the subpopulation of TRPA1-nociceptors could be evoked following defunctionalization of TRPV1-nociceptors by cutaneous application of high-concentration capsaicin. Two quadratic areas on each forearm were randomized to pretreatment with an 8% topical capsaicin patch or vehicle for 24h. Subsequently, areas were provoked by transdermal 1% topical capsaicin (TRPV1 agonist) or 10% topical allyl-isothiocyanate ('AITC', a TRPA1-agonist), delivered by 12mm Finn chambers. Evoked pain intensities were recorded during pretreatments and chemical provocations. Quantitative sensory tests were performed before and after provocations to assess changes of heat pain sensitivity. Imaging of vasomotor responses was used to assess neurogenic inflammation after the chemical provocations. In the capsaicin-pretreated areas both the subsequent 1% capsaicin- and 10% AITC-provoked pain intensities were inhibited by 92.9±2.5% and 86.9±5.0% (both: P<0.001), respectively. The capsaicin-ablated skin areas showed significant heat hypoalgesia at baseline (P<0.001) as well as heat antihyperalgesia, and inhibition of neurogenic inflammation evoked by both 1% capsaicin- and 10% AITC provocations (both: P<0.001). Ablation of capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1 and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses. The present study suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TPRV1 fibers.

Does short-term exposure to mobile phone base station signals increase symptoms in individuals who report sensitivity to electromagnetic fields? A double-blind randomized provocation study.

PubMed

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-11-01

Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself.

Self-reported dietary fructose intolerance in irritable bowel syndrome: Proposed diagnostic criteria.

PubMed

Berg, Leif Kyrre; Fagerli, Erik; Myhre, Arnt-Otto; Florholmen, Jon; Goll, Rasmus

2015-05-14

To study the criteria for self-reported dietary fructose intolerance (DFI) and to evaluate subjective global assessment (SGA) as outcome measure. Irritable bowel syndrome (IBS) patients were randomized in an open study design with a 2 wk run-in on a habitual IBS diet, followed by 12 wk with/without additional fructose-reduced diet (FRD). Daily registrations of stool frequency and consistency, and symptoms on a visual analog scale (VAS) were performed during the first 4 wk. SGA was used for weekly registrations during the whole study period. Provocation with high-fructose diet was done at the end of the registration period. Fructose breath tests (FBTs) were performed. A total of 182 subjects performed the study according to the protocol (88 FRD, 94 controls). We propose a new clinically feasible diagnostic standard for self-reported fructose intolerance. The instrument is based on VAS registrations of symptom relief on FRD combined with symptom aggravation upon provocation with fructose-rich diet. Using these criteria 43 of 77 patients (56%) in the present cohort of IBS patients had self-reported DFI. To improve the concept for clinical evaluation, we translated the SGA scale instrument to Norwegian and validated it in the context of the IBS diet regimen. The validation procedures showed a sensitivity, specificity and κ value for SGA detecting the self-reported DFI group by FRD response within the IBS patients of 0.79, 0.75 and 0.53, respectively. Addition of the provocation test yielded values of 0.84, 0.76 and 0.61, respectively. The corresponding validation results for FBT were 0.57, 0.34 and -0.13, respectively. FRD improves symptoms in a subgroup of IBS patients. A diet trial followed by a provocation test evaluated by SGA can identify most responders to FRD.

Abnormal hip physical examination findings in asymptomatic female soccer athletes

PubMed Central

Hunt, Devyani; Rho, Monica; Yemm, Ted; Fong, Kathryn; Brophy, Robert H.

2016-01-01

Purpose Examination of the hip provides information regarding risk for pre-arthritic hip disorders, knee injuries, and low back pain. The purpose of this study was to report a hip screening examination of asymptomatic female soccer athletes and to test the hypothesis that these findings vary by competition experience. Methods Asymptomatic females from a youth soccer club, a college, and a professional team were evaluated. Passive hip range of motion, hip abduction strength, and hip provocative tests were assessed. Data were compared for the grade/middle school, high school, college, and professional athletes. Results One hundred and seventy-two athletes with a mean age of 16.7 ± 5 years (range 10–30) participated. Professional athletes had less flexion (HF) for both hips (p < 0.0001) and less internal rotation (IR) for the preferred kicking leg (p < 0.05) compared to all other groups. Grade/middle school athletes had more external rotation in both hips as compared to all other groups (p < 0.0001). For the preferred kicking leg, collegiate athletes had less hip abduction strength as compared to other groups (p < 0.01). Positive provocative hip tests were found in 22 % of all players and 36 % of the professionals. In professionals, a positive provocative test was associated with ipsilateral decreased HF (p = 0.04). Conclusion Asymptomatic elite female soccer athletes with the most competition experience had less bilateral hip flexion and preferred kicking leg IR than less-experienced athletes. Positive provocative hip tests were found in 22 % of athletes. Future studies are needed to show whether these findings link to risk for intra-articular hip or lumbar spine and knee disorders. Level of evidence III. PMID:24150125

Does Short-Term Exposure to Mobile Phone Base Station Signals Increase Symptoms in Individuals Who Report Sensitivity to Electromagnetic Fields? A Double-Blind Randomized Provocation Study

PubMed Central

Eltiti, Stacy; Wallace, Denise; Ridgewell, Anna; Zougkou, Konstantina; Russo, Riccardo; Sepulveda, Francisco; Mirshekar-Syahkal, Dariush; Rasor, Paul; Deeble, Roger; Fox, Elaine

2007-01-01

Background Individuals with idiopathic environmental illness with attribution to electromagnetic fields (IEI-EMF) believe they suffer negative health effects when exposed to electromagnetic fields from everyday objects such as mobile phone base stations. Objectives This study used both open provocation and double-blind tests to determine if sensitive and control individuals experience more negative health effects when exposed to base station-like signals compared with sham. Methods Fifty-six self-reported sensitive and 120 control participants were tested in an open provocation test. Of these, 12 sensitive and 6 controls withdrew after the first session. The remainder completed a series of double-blind tests. Subjective measures of well-being and symptoms as well as physiological measures of blood volume pulse, heart rate, and skin conductance were obtained. Results During the open provocation, sensitive individuals reported lower levels of well-being in both the global system for mobile communication (GSM) and universal mobile telecommunications system (UMTS) compared with sham exposure, whereas controls reported more symptoms during the UMTS exposure. During double-blind tests the GSM signal did not have any effect on either group. Sensitive participants did report elevated levels of arousal during the UMTS condition, whereas the number or severity of symptoms experienced did not increase. Physiological measures did not differ across the three exposure conditions for either group. Conclusions Short-term exposure to a typical GSM base station-like signal did not affect well-being or physiological functions in sensitive or control individuals. Sensitive individuals reported elevated levels of arousal when exposed to a UMTS signal. Further analysis, however, indicated that this difference was likely to be due to the effect of order of exposure rather than the exposure itself. PMID:18007992

A systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy

PubMed Central

Pool, Jan J. M.; van Tulder, Maurits W.; Riphagen, Ingrid I.; de Vet, Henrica C. W.

2006-01-01

Clinical provocative tests of the neck, which position the neck and arm inorder to aggravate or relieve arm symptoms, are commonly used in clinical practice in patients with a suspected cervical radiculopathy. Their diagnostic accuracy, however, has never been examined in a systematic review. A comprehensive search was conducted in order to identify all possible studies fulfilling the inclusion criteria. A study was included if: (1) any provocative test of the neck for diagnosing cervical radiculopathy was identified; (2) any reference standard was used; (3) sensitivity and specificity were reported or could be (re-)calculated; and, (4) the publication was a full report. Two reviewers independently selected studies, and assessed methodological quality. Only six studies met the inclusion criteria, which evaluated five provocative tests. In general, Spurling’s test demonstrated low to moderate sensitivity and high specificity, as did traction/neck distraction, and Valsalva’s maneuver. The upper limb tension test (ULTT) demonstrated high sensitivity and low specificity, while the shoulder abduction test demonstrated low to moderate sensitivity and moderate to high specificity. Common methodological flaws included lack of an optimal reference standard, disease progression bias, spectrum bias, and review bias. Limitations include few primary studies, substantial heterogeneity, and numerous methodological flaws among the studies; therefore, a meta-analysis was not conducted. This review suggests that, when consistent with the history and other physical findings, a positive Spurling’s, traction/neck distraction, and Valsalva’s might be indicative of a cervical radiculopathy, while a negative ULTT might be used to rule it out. However, the lack of evidence precludes any firm conclusions regarding their diagnostic value, especially when used in primary care. More high quality studies are necessary in order to resolve this issue. PMID:17013656

Retrospective Comparison of Cardiac Testing and Results on Inpatients with Low Pretest Probability Compared with Moderate/High Pretest Probability for Coronary Artery Disease.

PubMed

Lear, Aaron; Huber, Merritt; Canada, Amy; Robertson, Jessica; Bosman, Evan; Zyzanski, Stephen

2018-01-01

To determine whether admission, and provocative stress testing of patients who have ruled out for acute coronary syndrome put patients with low-risk category for coronary artery disease (CAD) at risk for false-positive provocative stress testing and unnecessary coronary angiogram/imaging. A retrospective chart review was performed on patients between 30 and 70 years old, with no pre-existing diagnosis of CAD, admitted to observation or inpatient status chest pain or related complaints. Included patients were categorized based on Duke Clinical Score for pretest probability for CAD into either low-risk group, or moderate/high-risk group. The inpatient course was compared including whether provocative stress testing was performed; results of stress testing; whether patients underwent further coronary imaging; and what the results of the further imaging showed. 543 patients were eligible: 305 low pretest probability, and 238 moderate/high pretest probability. No difference was found in rate of stress testing relative risk (RR) = 1.01 (95% CI, 0.852 to 1.192; P = 0); rate of positive or equivocal stress tests between the 2 groups: RR = 0.653 (95% CI, 0.415 to 1.028; P = .07,). Low-pretest-probability patients had a lower likelihood of positive coronary imaging after stress test, RR = 0.061 (95% CI, 0.004 to 0.957; P = .001). Follow-up provocative testing of all patients admitted/observed after emergency department presentation with chest pain is unlikely to find CAD in patients with low pretest probability. Testing all low-probability patients puts them at increased risk for unnecessary invasive confirmatory testing. Further prospective testing is needed to confirm these retrospective results. © Copyright 2018 by the American Board of Family Medicine.

Test-retest Reliability in Reporting the Pain Induced by a Pain Provocation Test: Further Validation of a Novel Approach for Pain Drawing Acquisition and Analysis.

PubMed

Leoni, Diego; Falla, Deborah; Heitz, Carolin; Capra, Gianpiero; Clijsen, Ron; Egloff, Michele; Cescon, Corrado; Baeyens, Jean-Pierre; Barbero, Marco

2017-02-01

Pain drawings (PD) are frequently used in research to illustrate the pain response to pain provocation tests. However, there is a lack of data on the reliability in defining the extent and location of pain. We investigated the test-retest reliability in reporting an acute painful sensation induced by a pain provocation test using a novel approach for PD acquisition and analysis in healthy volunteers. Forty healthy volunteers participated. Each participant underwent 2 upper limb neurodynamic tests 1 (ULNT1), once to the point of pain onset (PO) and once until the point of submaximal pain (SP). After each ULNT1, participants completed 2 consecutive PD with an interval of 1 minute. Custom software was used to quantify the pain extent and analyze the pain overlap. The test-retest reliability of pain extent was examined using Intraclass Correlation Coefficient (ICC 2,1 ) and Bland-Altman plots. Pain location reliability was examined using the Jaccard similarity coefficient (JSC). The ICC values for PO and SP were 0.98 (95% CI: 0.96-0.99) and 0.97 (95% CI: 0.95-0.98), respectively. The mean difference and 95% limits of agreement (± 1.96 SD) in the Bland-Altman plots were 14 pixels (-1080;1110) for PO, and 145 (-1610;1900) for SP. The median JSCs (Q1;Q3) were 0.73 (0.64;0.80) for PO and 0.76 (0.65;0.79) for SP. Pain drawings is a reliable instrument to investigate pain extent and pain location in healthy individuals experiencing an acute painful sensation induced by a pain provocation test. © 2016 World Institute of Pain.

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming

2015-04-01

This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

PubMed

Fekete, Tibor; Rásó, Erzsébet; Pete, Imre; Tegze, Bálint; Liko, István; Munkácsy, Gyöngyi; Sipos, Norbert; Rigó, János; Györffy, Balázs

2012-07-01

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort. Copyright © 2011 UICC.

Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant.

PubMed

Goldberg, Jenna D; Zheng, Junting; Ratan, Ravin; Small, Trudy N; Lai, Kuan-Chi; Boulad, Farid; Castro-Malaspina, Hugo; Giralt, Sergio A; Jakubowski, Ann A; Kernan, Nancy A; O'Reilly, Richard J; Papadopoulos, Esperanza B; Young, James W; van den Brink, Marcel R M; Heller, Glenn; Perales, Miguel-Angel

2017-08-01

Infection, relapse, and GVHD can complicate allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although the effect of poor immune recovery on infection risk is well-established, there are limited data on the effect of immune reconstitution on relapse and survival, especially following T-cell depletion (TCD). To characterize the pattern of immune reconstitution in the first year after transplant and its effects on survival and relapse, we performed a retrospective study in 375 recipients of a myeloablative TCD allo-HSCT for hematologic malignancies. We noted that different subsets recover sequentially, CD8 + T cells first, followed by total CD4 + and naïve CD4 + T cells, indicating thymic recovery during the first year after HSCT. In the multivariate model, a fully HLA-matched donor and recovery of T-cell function, assessed by PHA response at 6 months, were the only factors independently associated with OS and EFS. In conclusion, T-cell recovery is an important predictor of outcome after TCD allo-HSCT.

Clinical relevance of endoscopic assessment of inflammation in ulcerative colitis: Can endoscopic evaluation predict outcomes?

PubMed Central

Mohammed, Noor; Subramanian, Venkataraman

2016-01-01

Ulcerative colitis (UC) is a chronic inflammatory bowel condition characterised by a relapsing and remitting course. Symptom control has been the traditional mainstay of medical treatment. It is well known that histological inflammatory activity persists despite adequate symptom control and absence of endoscopic inflammation. Current evidence suggests that presence of histological inflammation poses a greater risk of disease relapse and subsequent colorectal cancer risk. New endoscopic technologies hold promise for developing endoscopic markers of mucosal inflammation. Achieving endoscopic and histological remission appears be the future aim of medical treatments for UC. This review article aims to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation UC and its correlation with disease outcomes. PMID:27895420

Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis.

PubMed

Yamamoto, T; Shimoyama, T; Matsumoto, K

2015-09-01

No studies have monitored the levels of faecal calprotectin (FC) during mesalazine suppository therapy for proctitis in ulcerative colitis (UC). To evaluate the value of consecutive monitoring of FC in patients with UC during mesalazine suppository therapy. One hundred and sixty patients with active inflammation limited to the rectum were treated with mesalazine 1 g suppository once daily for 8 weeks. Patients who achieved clinical remission were advised to maintain the treatment, and were followed up for further 40 weeks. FC levels were measured every 8 weeks during the study. At week 8, 118 patients (74%) went into clinical remission, of whom 88 achieved endoscopic healing. The median FC level significantly decreased in patients with clinical and endoscopic remission (both P < 0.0001), while it did not change significantly in those without remission. Eighty (68%) of the 118 patients with remission continued the treatment. Twenty-four patients (30%) relapsed during the 40-week follow-up. In patients with clinical relapse, the median FC level elevated already 8 weeks before the diagnosis of relapse. In contrast, in patients who maintained remission it remained at a low level and did not significantly change during the follow-up. Elevated FC level (≥55 μg/g) was useful for the early diagnosis of relapse (88% sensitivity and 80% specificity). Faecal calprotectin may represent a useful biomarker for the assessment of disease activity in UC patients treated with mesalazine suppositories. Serial monitoring of faecal calprotectin appears to be valuable for the prediction and early diagnosis of relapse during maintenance therapy. © 2015 John Wiley & Sons Ltd.

Survivin as prognostic and predictive factor in patients treated with gemcitabine, dexamethasone, and cisplatin for relapsed or refractory aggressive NHL.

PubMed

el Aziz, Lamiss Mohamed Abd

2014-11-01

The prognosis of relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) after front-line therapy remains poor. The development of more effective and less toxic salvage regimens remains a major challenge. Survivin is a member of the family of inhibitors of apoptosis, and survivin was associated with short survival and bad prognosis. This study was to evaluate the efficacy of GDP regimen (gemcitabine, dexamethasone and cisplatin) on relapsed or refractory aggressive NHL and various prognostic factors with special emphasis on survivin and observe the . Forty-six patients with relapsed and refractory NHL, intermediate or high-grade NHL (Revised European American Lymphoma Classification), who at least one regimen were enrolled into this study, which was carried out at Department, , Tanta University from July 2012 to July 2014. The patients were treated with GDP regimen (gemcitabine 1,000 mg/m(2) on days one and eight, dexamethasone 40 mg on days 1-3, and cisplatin 25 mg/m(2) on days 1-3) every 3 weeks. The efficacy and adverse events were evaluated according to the WHO criteria. All patients were assessed for efficacy and toxicity. The overall response rate was 58.7 %. Fourteen patients showed a complete response, thirteen partial responses, twelve stable diseases, and seven progressive disease. The 24-month overall survival was 50.8 %. Survivin is associated with low overall response and shorter overall survival. Grade 3 anemia was observed in four patients, grade 3 leucopenia in six patients, grade 3 neutropenia in six patients, and grade 3 thrombocytopenia in four patients. Non-hematologic toxicity included grade 3 infection in four patients. The present schedule of GDP showed modest efficacy and mild toxicity in patients with relapsed or refractory aggressive NHL.

Dimensional personality traits and alcohol treatment outcome: a systematic review and meta-analysis.

PubMed

Foulds, James; Newton-Howes, Giles; Guy, Nicola H; Boden, Joseph M; Mulder, Roger T

2017-08-01

To identify dimensional personality traits associated with treatment outcome for patients with an alcohol use disorder (AUD). Systematic review and meta-analysis of clinical trials and longitudinal studies of ≥ 8 weeks in patients receiving treatment for AUD, in which the association between personality dimensions and treatment outcome was reported. Primary outcomes were relapse and alcohol consumption measures. Treatment retention was a secondary outcome. Eighteen studies, including 4783 subjects, were identified. Twelve studies used Cloninger's Temperament and Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI). Remaining studies used a broad range of other personality measures. Compared with non-relapsers, patients who relapsed had higher novelty-seeking [standardized mean difference in novelty-seeking score 0.28; 95% confidence interval (CI) = 0.12, 0.44], lower persistence (-0.30, 95% = CI -0.48, -0.12), lower reward dependence (-0.16, 95% CI = -0.31, -0.01) and lower cooperativeness (-0.23, 95% CI = -0.41, -0.04). Few studies reported on alcohol consumption outcomes, therefore findings for those outcomes were inconclusive. Lower novelty-seeking predicted better retention in treatment in two of three studies. Most studies reported findings only for those retained in treatment, and did not attempt to account for missing data; therefore, findings for the primary outcomes cannot be generalized to patients who dropped out of treatment. Studies using personality instruments other than the TCI or TPQ reported no consistent findings on the association between personality variables and treatment outcome. Among patients receiving treatment for an alcohol use disorder, those who relapse during follow-up have higher novelty-seeking, lower persistence, lower reward dependence and lower cooperativeness than those who do not relapse. © 2017 Society for the Study of Addiction.

Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

PubMed

Lublin, Fred D; Cofield, Stacey S; Cutter, Gary R; Conwit, Robin; Narayana, Ponnada A; Nelson, Flavia; Salter, Amber R; Gustafson, Tarah; Wolinsky, Jerry S

2013-03-01

A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. Copyright © 2013 American Neurological Association.

Longitudinal Social-Interpersonal Functioning among Higher-risk Responders to Acute-phase Cognitive Therapy for Recurrent Major Depressive Disorder

PubMed Central

Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.; Jarrett, Robin B.

2016-01-01

Background Social-interpersonal dysfunction increases disability in major depressive disorder (MDD). Here we clarified the durability of improvements in social-interpersonal functioning made during acute-phase cognitive therapy (CT), whether continuation CT (C-CT) or fluoxetine (FLX) further improved functioning, and relations of functioning with depressive symptoms and relapse/recurrence. Method Adult outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk of relapse (due to unstable or partial remission) were randomized to 8 months of C-CT, FLX, or pill placebo plus clinical management (PBO) and followed 24 additional months. We analyzed repeated measures of patients’ social adjustment, interpersonal problems, dyadic adjustment, depressive symptoms, and major depressive relapse/recurrence. Results Large improvements in social-interpersonal functioning occurring during acute-phase CT (median d=1.4) were maintained, with many patients (median=66%) scoring in normal ranges for 32 months. Social-interpersonal functioning did not differ significantly among C-CT, FLX, and PBO arms. Beyond concurrently measured residual symptoms, deterioration in social-interpersonal functioning preceded and predicted upticks in depressive symptoms and major depressive relapse/recurrence. Limitations Results may not generalize to other patient populations, treatment protocols, or measures of social-interpersonal functioning. Mechanisms of risk connecting poorer social-interpersonal functioning with depression were not studied. Conclusions Average improvements in social-interpersonal functioning among higher-risk responders to acute phase CT are durable for 32 months. After acute-phase CT, C-CT or FLX may not further improve social-interpersonal functioning. Among acute-phase CT responders, deteriorating social-interpersonal functioning provides a clear, measurable signal of risk for impending major depressive relapse/recurrence and opportunity for preemptive intervention. PMID:27104803

Longitudinal social-interpersonal functioning among higher-risk responders to acute-phase cognitive therapy for recurrent major depressive disorder.

PubMed

Vittengl, Jeffrey R; Clark, Lee Anna; Thase, Michael E; Jarrett, Robin B

2016-07-15

Social-interpersonal dysfunction increases disability in major depressive disorder (MDD). Here we clarified the durability of improvements in social-interpersonal functioning made during acute-phase cognitive therapy (CT), whether continuation CT (C-CT) or fluoxetine (FLX) further improved functioning, and relations of functioning with depressive symptoms and relapse/recurrence. Adult outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk of relapse (due to unstable or partial remission) were randomized to 8 months of C-CT, FLX, or pill placebo plus clinical management (PBO) and followed 24 additional months. We analyzed repeated measures of patients' social adjustment, interpersonal problems, dyadic adjustment, depressive symptoms, and major depressive relapse/recurrence. Large improvements in social-interpersonal functioning occurring during acute-phase CT (median d=1.4) were maintained, with many patients (median=66%) scoring in normal ranges for 32 months. Social-interpersonal functioning did not differ significantly among C-CT, FLX, and PBO arms. Beyond concurrently measured residual symptoms, deterioration in social-interpersonal functioning preceded and predicted upticks in depressive symptoms and major depressive relapse/recurrence. Results may not generalize to other patient populations, treatment protocols, or measures of social-interpersonal functioning. Mechanisms of risk connecting poorer social-interpersonal functioning with depression were not studied. Average improvements in social-interpersonal functioning among higher-risk responders to acute phase CT are durable for 32 months. After acute-phase CT, C-CT or FLX may not further improve social-interpersonal functioning. Among acute-phase CT responders, deteriorating social-interpersonal functioning provides a clear, measurable signal of risk for impending major depressive relapse/recurrence and opportunity for preemptive intervention. Copyright © 2016 Elsevier B.V. All rights reserved.