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.

[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.

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

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.

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.

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.

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.

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.

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.

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

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.

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

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

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

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

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.

Use of a Relapse Monitoring Board

PubMed Central

MacFadden, Wayne; Anand, Ravi; Khanna, Sumant; Rapaport, Mark H.; Haskins, J. Thomas; Turkoz, Ibrahim; Alphs, Larry

2011-01-01

Objective: Independent review boards can provide an objective appraisal of investigators' decisions and may be useful for determining complex primary outcomes, such as bipolar disorder relapse, in crossnational studies. This article describes the use of an independent, blinded relapse monitoring board to assess the primary outcome (relapse) in an international clinical trial of risperidone long-acting therapy adjunctive to standard-care pharmacotherapy for patients with bipolar disorder. Design: The fully autonomous relapse monitoring board was composed of a chair and two additional members—all psychiatrists and experts in the diagnostic, clinical, and therapeutic management of bipolar disorder. The relapse monitoring board met six times during the study to review patient relapse data and was charged with the responsibility of determining if the events described by investigators qualified as relapses. Additionally, the relapse monitoring board reviewed data for all randomized patients to identify any relapse events not recognized by investigators. Results: Primary efficacy results were similar and significant for investigator- and relapse monitoring board-determined relapses. Ten discrepancies were noted: two of the 42 investigator-determined relapses did not meet the intended clinical relapse threshold as determined by the relapse monitoring board; conversely, the relapse monitoring board confirmed eight relapse events not identified by investigators. The relapse monitoring board had no direct interactions with patients and had to rely on the accuracy of investigator assessments. Also, once an investigator determined a relapse and the patients discontinued the study, less information was available to the relapse monitoring board for relapse assessment. Conclusions: Use of the relapse monitoring board supported the validity of the study by incorporating a level of standardization to mitigate the risk that local practice in different cultures and medical systems

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

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

Cognitive reactivity to sad mood provocation and the prediction of depressive relapse.

PubMed

Segal, Zindel V; Kennedy, Sidney; Gemar, Michael; Hood, Karyn; Pedersen, Rebecca; Buis, Tom

2006-07-01

Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further

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.

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

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.

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

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.

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.

Percentage of positive prostate biopsies independently predicts biochemical outcome following radiation therapy for prostate cancer.

PubMed

Gabriele, Domenico; Garibaldi, Monica; Girelli, Giuseppe; Taraglio, Stefano; Duregon, Eleonora; Gabriele, Pietro; Guiot, Caterina; Bollito, Enrico

2016-06-01

This work aims to definitely show the ability of percentage of positive biopsy cores (%PC) to independently predict biochemical outcome beyond traditional pretreatment risk-factors in prostate cancer (PCa) patients treated with radiotherapy. A cohort of 2493 men belonging to the EUREKA-2 retrospective multicentric database on (PCa) and treated with external-beam radiation therapy (EBRT) as primary treatment comprised the study population (median follow-up 50 months). A Cox regression time to prostate-specific antigen (PSA) failure analysis was performed to evaluate the predictive power of %PC, both in univariate and multivariate settings, with age, pretreatment PSA, clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/- ADT as covariates. P statistics for %PC is lower than 0.001 both in univariate and multivariate models. %PC as a continuous variable yields an AUC of 69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21-50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical relapse (overall log-rank test P<0.0001), with biochemical progression free survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from 80% to 38%. We strongly affirm the usefulness of %PC information beyond main risk factors (PSA, staging and bGS) in predicting biochemical recurrence after EBRT for PCa. The stratification of patients according to %PC may be valuable to further discriminate cases with favourable or adverse prognosis.

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.

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

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer

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

Gee, Harriet E., E-mail: harriet.gee@sydney.edu.au; The Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW; Central Clinical School, Sydney Medical School, University of Sydney, NSW

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series ofmore » 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers—TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1—were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy–treated patients but not in untreated

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.

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.

Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

PubMed

Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

2011-01-01

Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

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

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.

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.

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.

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).

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

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.

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

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.

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

PubMed

Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

2010-01-01

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p < 0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

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.

Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

PubMed Central

Jokubaitis, Vilija G.; Trojano, Maria; Izquierdo, Guillermo; Grand’Maison, François; Oreja-Guevara, Celia; Boz, Cavit; Lugaresi, Alessandra; Girard, Marc; Grammond, Pierre; Iuliano, Gerardo; Fiol, Marcela; Cabrera-Gomez, Jose Antonio; Fernandez-Bolanos, Ricardo; Giuliani, Giorgio; Lechner-Scott, Jeannette; Cristiano, Edgardo; Herbert, Joseph; Petkovska-Boskova, Tatjana; Bergamaschi, Roberto; van Pesch, Vincent; Moore, Fraser; Vella, Norbert; Slee, Mark; Santiago, Vetere; Barnett, Michael; Havrdova, Eva; Young, Carolyn; Sirbu, Carmen-Adella; Tanner, Mary; Rutherford, Michelle; Butzkueven, Helmut

2012-01-01

Objectives We conducted a prospective study, MSBASIS, to assess factors leading to first treatment discontinuation in patients with a clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). Methods The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI) features and Expanded Disability Status Scale (EDSS) scores. Follow-up visits report relapses, EDSS scores, and the start and end dates of MS-specific therapies. We performed a multivariable survival analysis to determine factors within this dataset that predict first treatment discontinuation. Results A total of 2314 CIS patients from 44 centres were followed for a median of 2.7 years, during which time 1247 commenced immunomodulatory drug (IMD) treatment. Ninety percent initiated IMD after a diagnosis of MS was confirmed, and 10% while still in CIS status. Over 40% of these patients stopped their first IMD during the observation period. Females were more likely to cease medication than males (HR 1.36, p = 0.003). Patients treated in Australia were twice as likely to cease their first IMD than patients treated in Spain (HR 1.98, p = 0.001). Increasing EDSS was associated with higher rate of IMD cessation (HR 1.21 per EDSS unit, p<0.001), and intramuscular interferon-β-1a (HR 1.38, p = 0.028) and subcutaneous interferon-β-1a (HR 1.45, p = 0.012) had higher rates of discontinuation than glatiramer acetate, although this varied widely in different countries. Onset cerebral MRI features, age, time to treatment initiation or relapse on treatment were not associated with IMD cessation. Conclusion In this multivariable survival analysis, female sex, country of residence, EDSS change and IMD choice independently predicted time to first IMD cessation. PMID:22768046

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…

Cladribine tablets: in relapsing-remitting multiple sclerosis.

PubMed

Muir, Victoria J; Plosker, Greg L

2011-03-01

Cladribine, an immunosuppressant that selectively reduces peripheral lymphocyte levels, has potential as an oral therapy for relapsing-remitting multiple sclerosis. An oral (tablet) formulation is being investigated in clinical trials. In the large, well designed, phase III CLARITY trial, short-course treatment with oral cladribine (cumulative dose of 3.5 or 5.25 mg/kg) resulted in a significantly greater reduction in annualized relapse rates at 96 weeks compared with placebo in patients with relapsing-remitting multiple sclerosis. Improvements in the annualized relapse rate with oral cladribine were independent of key baseline patient characteristics which included age, sex, previous treatment with disease-modifying drugs and the number of relapses in the previous 12 months. In addition, a significantly higher proportion of patients were relapse-free at 96 weeks and there were significant reductions in the risk of 3-month sustained progression of disability in cladribine recipients compared with placebo recipients. The mean numbers of brain lesions on magnetic resonance imaging were also significantly reduced with cladribine compared with placebo in the CLARITY trial. Lymphocytopenia, herpes zoster infections and neoplasms (including malignancies) were more common in cladribine than placebo recipients.

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

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.

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…

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.

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.

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.

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.

[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.

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

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

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

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).

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.

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.

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.

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.

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

Extinction of relapsed fear does not require the basolateral amygdala.

PubMed

Lingawi, Nura W; Westbrook, R Frederick; Laurent, Vincent

2017-03-01

It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear. That is, extinction of spontaneously recovered or renewed fear was spared by BLA inactivation. Yet, this BLA-independent learning of extinction did not protect against further relapse: extinction of relapsed fear conducted without BLA activity was still likely to return after the passage of time or a shift in physical context. These findings have important clinical implications. They indicate that pharmacological agents with anxiolytic properties may disrupt initial cue-exposure therapy but may be useful when therapy is again needed due to relapse. However, they also suggest that these agents will not protect against further relapse, implying the need for developing drugs that target other brain regions involved in fear inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Smoking increases the risk of relapse after successful tuberculosis treatment.

PubMed

d'Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha

2008-08-01

Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001-2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Smoking (OR 2.53, 95% CI 1.23-5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46-8.93) were found to be independently associated with relapse of tuberculosis. Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs.

Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.

PubMed

Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang

2015-09-01

To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.

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.

Mood Reactivity Rather than Cognitive Reactivity Is Predictive of Depressive Relapse: A Randomized Study with 5.5-Year Follow-Up

ERIC Educational Resources Information Center

van Rijsbergen, Gerard D.; Bockting, Claudi L. H.; Burger, Huibert; Spinhoven, Philip; Koeter, Maarten W. J.; Ruhe, Henricus G.; Hollon, Steven D.; Schene, Aart H.

2013-01-01

Objective: The current study examined whether cognitive reactivity, cognitive extremity reactivity, and mood reactivity following mood provocation predicted relapse in depression over 5.5 years. Additionally, this study was the 1st to examine whether changes in cognitive reactivity and mood reactivity following preventive cognitive therapy (PCT)…

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

Hazardous Alcohol Drinking as Predictor of Smoking Relapse (3-, 6-, and 12-Months Follow-Up) by Gender.

PubMed

Rodríguez-Cano, Rubén; López-Durán, Ana; Martínez-Vispo, Carmela; Martínez, Úrsula; Fernández Del Río, Elena; Becoña, Elisardo

2016-12-01

Diverse studies have found a relation between alcohol consumption and smoking relapse. Few studies have analyzed the relation of smoking relapse with pretreatment alcohol consumption and gender differences. The main purpose of this study is to analyze the influence of alcohol consumption in smoking relapse over 12 months (3-, 6-, and 12-months follow-up) and to determine possible gender differences. The sample included 374 smokers who quit smoking by participating in a psychological smoking cessation treatment. We assessed hazardous pretreatment alcohol drinking (AUDIT), cigarette consumption (FTND; number of cigarettes) and sociodemographic variables. Higher scores on hazardous pretreatment alcohol drinking predict smoking relapse at 3-, 6-, and 12-months after smoking cessation. In males, higher scores on hazardous pretreatment alcohol drinking predict relapse at 6 and at 12 months. In females, higher scores on hazardous pretreatment alcohol drinking predict tobacco relapse at 3 months. Hazardous pretreatment alcohol drinking predicts relapse at all intervals after smoking cessation (3-, 6-, and 12-months follow-up). However, the influence of hazardous pretreatment alcohol drinking on smoking relapse differs as a function of gender, as it is a short-term predictor in women (3 months) and a long-term predictor in men (6 and 12 months). Copyright © 2016 Elsevier Inc. All rights reserved.

A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 2: factors that 'pull' the gambler away from relapse.

PubMed

Oakes, J; Pols, R; Battersby, M; Lawn, S; Pulvirenti, M; Smith, D

2012-09-01

This study aimed to develop an empirically based description of relapse in Electronic Gaming Machine (EGM) problem gambling (PG) by describing the processes and factors that 'pull' the problem gambler away from relapse contrasted with the 'push' towards relapse. These conceptualisations describe two opposing, interacting emotional processes occurring within the problem gambler during any relapse episode. Each relapse episode comprises a complex set of psychological and social behaviours where many factors interact sequentially and simultaneously within the problem gambler to produce a series of mental and behaviour events that end (1) with relapse where 'push' overcomes 'pull' or (2) continued abstinence where 'pull' overcomes 'push'. Four focus groups comprising thirty participants who were EGM problem gamblers, gamblers' significant others, therapists and counsellors described their experiences and understanding of relapse. The groups were recorded, recordings were then transcribed and analysed using thematic textual analysis. It was established that vigilance, motivation to commit to change, positive social support, cognitive strategies such as remembering past gambling harms or distraction techniques to avoid thinking about gambling to enable gamblers to manage the urge to gamble and urge extinction were key factors that protected against relapse. Three complementary theories emerged from the analysis. Firstly, a process of reappraisal of personal gambling behaviour pulls the gambler away from relapse. This results in a commitment to change that develops over time and affects but is independent of each episode of relapse. Secondly, relapse may be halted by interacting factors that 'pull' the problem gambler away from the sequence of mental and behavioural events, which follow the triggering of the urge and cognitions to gamble. Thirdly, urge extinction and apparent 'cure' is possible for EGM gambling. This study provides a qualitative, empirical model for

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.

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.

Narcotic Independence After Pancreatic Duct Stenting Predicts Narcotic Independence After Lateral Pancreaticojejunostomy for Chronic Pancreatitis.

PubMed

Kwon, Richard S; Young, Benjamin E; Marsteller, William F; Lawrence, Christopher; Wu, Bechien U; Lee, Linda S; Mullady, Daniel; Klibansky, David A; Gardner, Timothy B; Simeone, Diane M

2016-09-01

This study aimed to determine if the improved pain response to endoscopic retrograde cholangiopancreatogrphy (ERCP) and pancreatic stent placement (EPS) predicts pain response in patients with chronic pancreatitis after modified lateral pancreaticojejunostomy (LPJ). A multi-institutional, retrospective review of patients who underwent successful EPS before LPJ between 2001 and 2010 was performed. The primary outcome was narcotic independence (NI) within 2 months after ERCP or LPJ. A total of 31 narcotic-dependent patients with chronic pancreatitis underwent successful EPS before LPJ. Ten (32%) achieved post-LPJ NI (median follow-up, 8.5 months; interquartile range [IQR], 2-38 months). Eight (80%) of 10 patients with NI post-ERCP achieved NI post-LPJ. Two (10%) without NI post-ERCP achieved NI post-LPJ. Narcotic independence post-EPS was associated strongly with NI post-LPJ with an odds ratio of 38 (P = 0.0025) and predicted post-LPJ NI with a sensitivity, specificity, positive predictive value, and negative predictive value of 80%, 90.5%, 80%, and 90.5%, respectively. Narcotic independence after EPS is associated with NI after LPJ. Failure to achieve NI post-ERCP predicts failure to achieve NI post-LPJ. These results support the need for larger studies to confirm the predictive value of pancreatic duct stenting for better selection of chronic pancreatitis patients who will benefit from LPJ.

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

Relapses vs. reactions in multibacillary leprosy: proposal of new relapse criteria.

PubMed

Linder, Katharina; Zia, Mutaher; Kern, Winfried V; Pfau, Ruth K M; Wagner, Dirk

2008-03-01

To compare a new scoring system for multibacillary (MB) leprosy relapses, which combines time factor, risk factors and clinical presentation at relapse, to WHO criteria. Data were collected on all relapses diagnosed between 1998 and 2004 at the Marie-Adelaide-Centre in Karachi, Pakistan, including case histories, clinical manifestations, follow-up, bacterial indices, treatment and contacts. For the diagnosis of MB relapses a simple scoring system was developed and validated on a data-set of mouse foot pads (MFP)-confirmed relapses (Leprosy Reviews, 76, 2005, 241). Its sensitivity was further evaluated in the Karachi relapse cohort. The P-value was calculated with McNemar's test with continuity correction. The new scoring system that combines time factor, risk factors and clinical presentation at relapse had a higher sensitivity in MFP-confirmed relapses than the WHO-criteria (95%vs. 65%, P < 0.01). The sensitivity of the scoring system was also significantly higher than the WHO criteria in the 57 cases of MB-relapses diagnosed in Karachi (72%vs. 54%, P < 0.05). This new simple scoring system for diagnosing MB-relapses in leprosy should be further validated in a prospective study to confirm its superior sensitivity and to evaluate the specificity of these criteria by using MFP-confirmation for patients presenting with signs of activity after treatment.

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.

Motivated independence? Implicit party identity predicts political judgments among self-proclaimed Independents.

PubMed

Hawkins, Carlee Beth; Nosek, Brian A

2012-11-01

Reporting an Independent political identity does not guarantee the absence of partisanship. Independents demonstrated considerable variability in relative identification with Republicans versus Democrats as measured by an Implicit Association Test (IAT; M = 0.10, SD = 0.47). To test whether this variation predicted political judgment, participants read a newspaper article describing two competing welfare (Study 1) or special education (Study 2) policies. The authors manipulated which policy was proposed by which party. Among self-proclaimed Independents, those who were implicitly Democratic preferred the liberal welfare plan, and those who were implicitly Republican preferred the conservative welfare plan. Regardless of the policy details, these implicit partisans preferred the policy proposed by "their" party, and this effect occurred more strongly for implicit than explicit plan preference. The authors suggest that implicitly partisan Independents may consciously override some partisan influence when making explicit political judgments, and Independents may identify as such to appear objective even when they are not.

Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients

PubMed Central

Corrias, Maria Valeria; Levreri, Isabella; Scaruffi, Paola; Raffaghello, Lizzia; Carlini, Barbara; Bocca, Paola; Prigione, Ignazia; Stigliani, Sara; Amoroso, Loredana; Ferrone, Soldano; Pistoia, Vito

2012-01-01

The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy. PMID:21660451

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.

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…

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

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

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.

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.

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.

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

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

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

Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor.

PubMed

Boshuisen, Kim; Schmidt, Dieter; Uiterwaal, Cuno S P M; Arzimanoglou, Alexis; Braun, Kees P J; Study Group, TimeToStop

2014-09-01

It was recently suggested that early postoperative seizure relapse implicates a failure to define and resect the epileptogenic zone, that late recurrences reflect the persistence or re-emergence of epileptogenic pathology, and that early recurrences are associated with poor treatment response. Timing of antiepileptic drugs withdrawal policies, however, have never been taken into account when investigating time to relapse following epilepsy surgery. Of the European paediatric epilepsy surgery cohort from the "TimeToStop" study, all 95 children with postoperative seizure recurrence following antiepileptic drug (AED) withdrawal were selected. We investigated how time intervals from surgery to AED withdrawal, as well as other previously suggested determinants of (timing of) seizure recurrence, related to time to relapse and to relapse treatability. Uni- and multivariable linear and logistic regression models were used. Based on multivariable analysis, a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse. Based on univariable analysis, incomplete resection of the epileptogenic zone related to a shorter time to recurrence. Timing of recurrence was not related to the chance of regaining seizure freedom after reinstallation of medical treatment. For children in whom AED reduction is initiated following epilepsy surgery, the time to relapse is largely influenced by the timing of AED withdrawal, rather than by disease or surgery-specific factors. We could not confirm a relationship between time to recurrence and treatment response. Timing of AED withdrawal should be taken into account when studying time to relapse following epilepsy surgery, as early withdrawal reveals more rapidly whether surgery had the intended curative effect, independently of the other factors involved.

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

Delay discounting rates: a strong prognostic indicator of smoking relapse.

PubMed

Sheffer, Christine E; Christensen, Darren R; Landes, Reid; Carter, Larry P; Jackson, Lisa; Bickel, Warren K

2014-11-01

Recent evidence suggests that several dimensions of impulsivity and locus of control are likely to be significant prognostic indicators of relapse. One-hundred and thirty-one treatment seeking smokers were enrolled in six weeks of multi-component cognitive-behavioral therapy with eight weeks of nicotine replacement therapy. Cox proportional hazard regressions were used to model days to relapse with each of the following: delay discounting of $100, delay discounting of $1000, six subscales of the Barratt Impulsiveness Scale (BIS), Rotter's Locus of Control (RLOC), Fagerstrom's Test for Nicotine Dependence (FTND), and the Perceived Stress Scale (PSS). Hazard ratios for a one standard deviation increase were estimated with 95% confidence intervals for each explanatory variable. Likelihood ratios were used to examine the level of association with days to relapse for different combinations of the explanatory variables while accounting for nicotine dependence and stress level. These analyses found that the $100 delay discounting rate had the strongest association with days to relapse. Further, when discounting rates were combined with the FTND and PSS, the associations remained significant. When the other measures were combined with the FTND and PSS, their associations with relapse non-significant. These findings indicate that delay discounting is independently associated with relapse and adds to what is already accounted for by nicotine dependence and stress level. They also signify that delay discounting is a productive new target for enhancing treatment for tobacco dependence. Consequently, adding an intervention designed to decrease discounting rates to a comprehensive treatment for tobacco dependence has the potential to decrease relapse rates. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

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.

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.

High BAALC copy numbers in peripheral blood prior to allogeneic transplantation predict early relapse in acute myeloid leukemia patients.

PubMed

Jentzsch, Madlen; Bill, Marius; Grimm, Juliane; Schulz, Julia; Goldmann, Karoline; Beinicke, Stefanie; Häntschel, Janine; Pönisch, Wolfram; Franke, Georg-Nikolaus; Vucinic, Vladan; Behre, Gerhard; Lange, Thoralf; Niederwieser, Dietger; Schwind, Sebastian

2017-10-20

High BAALC expression levels at acute myeloid leukemia diagnosis have been linked to adverse outcomes. Recent data indicate that high BAALC expression levels may also be used as marker for residual disease following acute myeloid leukemia treatment. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment for acute myeloid leukemia patients. However, disease recurrence remains a major clinical challenge and identification of high-risk patients prior to HSCT is crucial to improve outcomes. We performed absolute quantification of BAALC copy numbers in peripheral blood prior (median 7 days) to HSCT in complete remission (CR) or CR with incomplete peripheral recovery in 82 acute myeloid leukemia patients using digital droplet PCR (ddPCR) technology. An optimal cut-off of 0.14 BAALC / ABL1 copy numbers was determined and applied to define patients with high or low BAALC / ABL1 copy numbers. High pre-HSCT BAALC / ABL1 copy numbers significantly associated with higher cumulative incidence of relapse and shorter overall survival in univariable and multivariable models. Patients with high pre-HSCT BAALC / ABL1 copy numbers were more likely to experience relapse within 100 days after HSCT. Evaluation of pre-HSCT BAALC / ABL1 copy numbers in peripheral blood by ddPCR represents a feasible and rapid way to identify acute myeloid leukemia patients at high risk of early relapse after HSCT. The prognostic impact was also observed independently of other known clinical, genetic, and molecular prognosticators. In the future, prospective studies should evaluate whether acute myeloid leukemia patients with high pre-HSCT BAALC / ABL1 copy numbers benefit from additional treatment before or early intervention after HSCT.

High BAALC copy numbers in peripheral blood prior to allogeneic transplantation predict early relapse in acute myeloid leukemia patients

PubMed Central

Jentzsch, Madlen; Bill, Marius; Grimm, Juliane; Schulz, Julia; Goldmann, Karoline; Beinicke, Stefanie; Häntschel, Janine; Pönisch, Wolfram; Franke, Georg-Nikolaus; Vucinic, Vladan; Behre, Gerhard; Lange, Thoralf; Niederwieser, Dietger; Schwind, Sebastian

2017-01-01

High BAALC expression levels at acute myeloid leukemia diagnosis have been linked to adverse outcomes. Recent data indicate that high BAALC expression levels may also be used as marker for residual disease following acute myeloid leukemia treatment. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment for acute myeloid leukemia patients. However, disease recurrence remains a major clinical challenge and identification of high-risk patients prior to HSCT is crucial to improve outcomes. We performed absolute quantification of BAALC copy numbers in peripheral blood prior (median 7 days) to HSCT in complete remission (CR) or CR with incomplete peripheral recovery in 82 acute myeloid leukemia patients using digital droplet PCR (ddPCR) technology. An optimal cut-off of 0.14 BAALC/ABL1 copy numbers was determined and applied to define patients with high or low BAALC/ABL1 copy numbers. High pre-HSCT BAALC/ABL1 copy numbers significantly associated with higher cumulative incidence of relapse and shorter overall survival in univariable and multivariable models. Patients with high pre-HSCT BAALC/ABL1 copy numbers were more likely to experience relapse within 100 days after HSCT. Evaluation of pre-HSCT BAALC/ABL1 copy numbers in peripheral blood by ddPCR represents a feasible and rapid way to identify acute myeloid leukemia patients at high risk of early relapse after HSCT. The prognostic impact was also observed independently of other known clinical, genetic, and molecular prognosticators. In the future, prospective studies should evaluate whether acute myeloid leukemia patients with high pre-HSCT BAALC/ABL1 copy numbers benefit from additional treatment before or early intervention after HSCT. PMID:29152132

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.

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

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…

Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials.

PubMed

Batelaan, Neeltje M; Bosman, Renske C; Muntingh, Anna; Scholten, Willemijn D; Huijbregts, Klaas M; van Balkom, Anton J L M

2017-09-13

Objectives  To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy. Design  Systematic review and meta-analyses of relapse prevention trials. Data sources  PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016). Study selection  Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse. Data extraction  Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool. Results  The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of

[Relapse: causes and consequences].

PubMed

Thomas, P

2013-09-01

Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Lymph node ratio may predict relapse free survival and overall survival in patients with stage II & III colorectal carcinoma.

PubMed

Zekri, Jamal; Ahmad, Imran; Fawzy, Ehab; Elkhodary, Tawfik R; Al-Gahmi, Aboelkhair; Hassouna, Ashraf; El Sayed, Mohamed E; Ur Rehman, Jalil; Karim, Syed M; Bin Sadiq, Bakr

2015-01-01

Lymph node ratio (LNR) defined as the number of lymph nodes (LNs) involved with metastases divided by number of LNs examined, has been shown to be an independent prognostic factor in breast, stomach and various other solid tumors. Its significance as a prognostic determinant in colorectal cancer (CRC) is still under investigation. This study investigated the prognostic value of LNR in patients with resected CRC. We retrospectively ex- amined 145 patients with stage II & III CRC diagnosed and treated at a single institution during 9 years pe- riod. Patients were grouped according to LNR in three groups. Group 1; LNR < 0.05, Group 2; LNR = 0.05-0.19 & Group 3 > 0.19. Chi square, life table analysis and multivariate Cox regression were used for statistical analysis. On multivariate analysis, number of involved LNs (NILN) (HR = 1.15, 95% CI 1.055-1.245; P = 0.001) and pathological T stage (P = 0.002) were statistically significant predictors of relapse free survival (RFS). LNR as a continuous variable (but not as a categorical variable) was statistically significant predictor of RFS (P = 0.02). LNR was also a statistically significant predictor of overall survival (OS) (P = 0.02). LNR may predict RFS and OS in patients with resected stage II & III CRC. Studies with larger cohorts and longer follow up are needed to further examine and validate theprognostic value of LNR.

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.

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

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

Binary logistic regression modelling: Measuring the probability of relapse cases among drug addict

NASA Astrophysics Data System (ADS)

Ismail, Mohd Tahir; Alias, Siti Nor Shadila

2014-07-01

For many years Malaysia faced the drug addiction issues. The most serious case is relapse phenomenon among treated drug addict (drug addict who have under gone the rehabilitation programme at Narcotic Addiction Rehabilitation Centre, PUSPEN). Thus, the main objective of this study is to find the most significant factor that contributes to relapse to happen. The binary logistic regression analysis was employed to model the relationship between independent variables (predictors) and dependent variable. The dependent variable is the status of the drug addict either relapse, (Yes coded as 1) or not, (No coded as 0). Meanwhile the predictors involved are age, age at first taking drug, family history, education level, family crisis, community support and self motivation. The total of the sample is 200 which the data are provided by AADK (National Antidrug Agency). The finding of the study revealed that age and self motivation are statistically significant towards the relapse cases..

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.

Lord Byron's death: a case of late malarial relapse?

PubMed

Tsiamis, Costas; Piperaki, Evangelia Theophano; Kalantzis, George; Poulakou Rebelakou, Effie; Tompros, Nikolaos; Thalassinou, Eleni; Spilipoulou, Chara; Tsakris, Athanassios

2015-09-01

The study examines the pathological circumstances related to Byron's death, the primary issue being malaria. Lord Byron died during the Greek War of Independence against the Ottoman Empire, in Messolonghi on 19 April 1824. Byron's medical profile consists of recurrent onsets of fever, which gave rise to the issue of malaria relapses. According to Byron's letters he reported crises of fever in Greece (1810), Malta (1811), Italy (1817-1819) and England. Evidence from Byron's autopsy, specifically the absence of hepatosplenomegaly, does not support a hypothetical diagnosis of malaria. Nonetheless, the relapsing fevers cannot be ignored and the same applies to the possibility of malaria relapse or re-infection in line with the endemic nature of the Messolonghi area. Our research on the chronologies of Byron's reported fevers found that new attacks occurred at intervals of 540 days on average. Moreover, the most outstanding feature of Plasmodium vivax and Plasmodium ovale is their ability to form dormant forms of hypnozoites in the liver which, when reactivated (110-777 days), cause true relapses of clinical disease. Of course, an ex post facto diagnosis is under debate, because the diagnosis is not clinical but microscopic. Byron's example raises alarm over a current medical problem, i.e. the diagnosis of unexplained fevers, and the need for a detailed travel or immigration history, which will include malaria in the differential diagnosis.

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

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

[Relapse prevention in drug addicts].

PubMed

Rácz, József

2013-12-01

The literature review deals with methods of relapse prevention. Relapse prevention is the key in the treatment of clients with drug addictions according to the transtheoretical model of change. If relapse prevention is more effective then not only the relapse would be prevented, but the client would leave the circulus vitiosus of relapses. Among psychotherapies cognitive behavioural methods are proven effective. Shorter forms of cognitive therapies are also available: for example, cognitive bias modification. Pharmacotherapy partly decreases craving of the clients or ceases the effects of psychoactive substances. Specific pharmacotherapeutic methods prevent relapses in a non-abstinent treatment design. Here the goal is not the abstinence in a short time, but the reduction of harms associated with drug use. In this way, a new target group of drug users can be involved in treatment.

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

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

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.

Social settings and addiction relapse.

PubMed

Walton, M A; Reischl, T M; Ramanthan, C S

1995-01-01

Despite addiction theorists' acknowledgment of the impact of environmental factors on relapse, researchers have not adequately investigated these influences. Ninety-six substance users provided data regarding their perceived risk for relapse, exposure to substances, and involvement in reinforcing activities. These three setting attributes were assessed in their home, work, and community settings. Reuse was assessed 3 months later. When controlling for confounding variables, aspects of the home settings significantly distinguished abstainers from reusers; perceived risk for relapse was the strongest predictor of reuse. Exposure to substances and involvement in reinforcing activities were not robust reuse indicators. The work and community settings were not significant determinants of reuse. These findings offer some initial support for the utility of examining social settings to better understand addiction relapse and recovery. Identification of setting-based relapse determinants provides concrete targets for relapse prevention interventions.

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.

Cytomegalovirus reactivation is associated with a lower rate of early relapse in myeloid malignancies independent of in-vivo T cell depletion strategy.

PubMed

Hilal, Talal; Slone, Stacey; Peterson, Shawn; Bodine, Charles; Gul, Zartash

2017-06-01

The association between cytomegalovirus (CMV) reactivation and relapse risk has not been evaluated in relation to T cell depletion strategies. We evaluated 93 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and analyzed the association between T cell depletion strategies with the cumulative incidence of relapse and CMV reactivation. A total of 33% of patients who received ATG vs. 34% who received alemtuzumab developed CMV reactivation. The cumulative incidence of relapse was 3% at 1year and 20% at 3 years in patients with CMV reactivation vs. 30% at 1year and 38% at 3 years in patients without CMV reactivation (p=0.02). When analyzed separately, this effect persisted in the myeloid, but not the lymphoid group. There was a numerical trend towards increased non-relapse mortality (NRM) in patients with CMV reactivation, especially in the myeloid group. The choice of T cell depleting agent and the rate of CMV reactivation were not associated with different overall survival (OS) rates. These results suggest that the choice of T cell depletion strategy may have similar effects on rates of CMV reactivation, disease relapse, and survival. Further studies examining these variables in patients not exposed to in-vivo T cell depleting agents may be of interest. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Cost of Relapse in Schizophrenia.

PubMed

Pennington, Mark; McCrone, Paul

2017-09-01

Schizophrenia is a chronic and debilitating mental illness characterised by periods of relapse that require resource intensive management. Quantifying the cost of relapse is central to the evaluation of the cost effectiveness of treating schizophrenia. We aimed to undertake a comprehensive search of the available literature on the cost of relapse. We performed a search on multiple databases (MEDLINE, Embase, PsycINFO and Health Management Information Consortium) for any study reporting a cost of relapse or data from which such a cost could be calculated. Costs are reported in 2015 international dollars. We found 16 studies reporting costs associated with relapse over a defined period of time and identified a cost associated with hospitalisation for relapse in 43 studies. Eight clinical decision analyses also provided cost estimates. Studies from the US report excess costs of relapse of $6033-$32,753 (2015 Purchasing Power Parity dollars [PPP$]) over periods of 12-15 months. European studies report excess costs of $8665-$18,676 (2015 PPP$) over periods of 6-12 months. Estimates of the cost of hospitalisation for relapse are more diverse, and associated with marked differences in typical length of stay across jurisdictions. Wide ranges in the estimated cost of relapse may reflect differences in sample section and relapse definition as well as practice styles and differences in resource costs. Selection of the most appropriate cost estimate should be guided by the definition of relapse and the analysis setting.

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.

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

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.

Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis.

PubMed

Kalinina Ayuso, Viera; van de Winkel, Evelyne Leonce; Rothova, Aniki; de Boer, Joke Helena

2011-02-01

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a

[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

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.

Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia.

PubMed

Zhao, Hongli; Zhao, Yanqiu; Zhang, Yingmei; Hou, Jinxiao; Yang, Huiyuan; Cao, Fenglin; Yang, Yiju; Hou, Wenyi; Sun, Jiayue; Jin, Bo; Fu, Jinyue; Li, Haitao; Wang, Ping; Ge, Fei; Zhou, Jin

2018-03-01

Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 10 9 /L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 10 9 /L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

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.

Late smoking relapse among adolescent quitters.

PubMed

Peterson, Arthur V; Marek, Patrick M

2017-02-01

Whereas some data are available about late smoking relapse among adult quitters, there are none for teen quitters. This study is a 6-year follow-up of teen quitters (n=253) for whom we collected (retrospectively) data on the extent and timing of relapse. We found that even after a strictly defined quit (six-months prolonged abstinence) at one year, substantial relapse occurred both early and late: the majority (55%) of relapses occurred after the 0-1year interval after having quit. These findings have implication for the need for research into the relapse process for teen quitters, and for the need to develop interventions for teens (as for adults) to prevent (early and) late relapse. Copyright © 2016. Published by Elsevier Ltd.

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.

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

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.

Stimulus-reinforcer relations established during training determine resistance to extinction and relapse via reinstatement.

PubMed

Bai, John Y H; Jonas Chan, C K; Elliffe, Douglas; Podlesnik, Christopher A

2016-11-01

The baseline rate of a reinforced target response decreases with the availability of response-independent sources of alternative reinforcement; however, resistance to disruption and relapse increases. Because many behavioral treatments for problem behavior include response-dependent reinforcement of alternative behavior, the present study assessed whether response-dependent alternative reinforcement also decreases baseline response rates but increases resistance to extinction and relapse. We reinforced target responding at equal rates across two components of a multiple schedule with pigeons. We compared resistance to extinction and relapse via reinstatement of (1) a target response trained concurrently with a reinforced alternative response in one component with (2) a target response trained either concurrently or in separate components from the alternative response across conditions. Target response rates trained alone in baseline were higher but resistance to extinction and relapse via reinstatement tests were greater after training concurrently with the alternative response. In another assessment, training target and alternative responding together, but separating them during extinction and reinstatement tests, produced equal resistance to extinction and relapse. Together, these findings are consistent with behavioral momentum theory-operant response-reinforcer relations determined baseline response rates but Pavlovian stimulus-reinforcer relations established during training determined resistance to extinction and relapse. These findings imply that reinforcing alternative behavior to treat problem behavior could initially reduce rates but increase persistence. © 2016 Society for the Experimental Analysis of Behavior.

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.

Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

PubMed

Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2014-02-01

Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Outcomes of treatment for relapsed acute lymphoblastic leukaemia in children with Down syndrome.

PubMed

Meyr, Franziska; Escherich, Gabriele; Mann, Georg; Klingebiel, Thomas; Kulozik, Andreas; Rossig, Claudia; Schrappe, Martin; Henze, Günter; von Stackelberg, Arend; Hitzler, Johann

2013-07-01

Children with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of survival and causes of treatment failure were determined for 49 children with DS and a matched cohort of 98 children without DS among 2160 children treated for relapsed ALL in clinical trials conducted by the Berlin-Frankfurt-Münster ALL Relapse Study Group between 1983 and 2012. Despite more favourable ALL relapse characteristics, children with DS experienced lower event-free (EFS) and overall survival (OS) than the control group without DS (EFS 17 ± 08% vs. non-DS 41 ± 06%, P = 0·006; OS 17 ± 09% vs. non-DS 51 ± 06%, P < 0·001). Children with DS developed more frequently fatal complications of treatment (34 ± 07% vs. non-DS 10 ± 04%, P < 0·001). During the last decade, EFS and OS were no longer significantly different in children with and without DS (EFS 31 ± 09% vs. 36 ± 09%, P = 0·399; OS 31 ± 12% vs. 53 ± 09%, P = 0·151). DS proved an independent prognostic factor of outcome after ALL relapse. Induction deaths and treatment-related mortality but not subsequent relapse were the main barrier to successful outcomes of relapse therapy in children with DS. © 2013 John Wiley & Sons Ltd.

Predicting Functional Independence Measure Scores During Rehabilitation with Wearable Inertial Sensors

PubMed Central

Sprint, Gina; Cook, Diane J.; Weeks, Douglas L.; Borisov, Vladimir

2016-01-01

Evaluating patient progress and making discharge decisions regarding inpatient medical rehabilitation rely upon standard clinical assessments administered by trained clinicians. Wearable inertial sensors can offer more objective measures of patient movement and progress. We undertook a study to investigate the contribution of wearable sensor data to predict discharge functional independence measure (FIM) scores for 20 patients at an inpatient rehabilitation facility. The FIM utilizes a 7-point ordinal scale to measure patient independence while performing several activities of daily living, such as walking, grooming, and bathing. Wearable inertial sensor data were collected from ecological ambulatory tasks at two time points mid-stay during inpatient rehabilitation. Machine learning algorithms were trained with sensor-derived features and clinical information obtained from medical records at admission to the inpatient facility. While models trained only with clinical features predicted discharge scores well, we were able to achieve an even higher level of prediction accuracy when also including the wearable sensor-derived features. Correlations as high as 0.97 for leave-one-out cross validation predicting discharge FIM motor scores are reported. PMID:27054054

TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.

PubMed

Yáñez, Yania; Hervás, David; Grau, Elena; Oltra, Silvestre; Pérez, Gema; Palanca, Sarai; Bermúdez, Mar; Márquez, Catalina; Cañete, Adela; Castel, Victoria

2016-03-01

In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, P; Stead, L F; West, R; Jarvis, M

2005-01-25

Several treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. There are interventions designed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction group trials register in September 2004 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow up of six months. We included smokers who quit on their own, or were undergoing enforced abstinence, or who were participating in treatment programmes. We included trials that compared relapse prevention interventions to a no intervention control, or that compared a cessation programme with additional relapse prevention components to a cessation programme alone. Studies were screened and data extracted by one author and checked by a second. Disagreements were resolved by discussion or referral to a third author. Forty studies met inclusion criteria, but were heterogeneous in terms of populations and interventions. We considered studies that randomized abstainers separately from studies that randomized participants prior to their quit date. We detected no benefit of brief and 'skills-based' relapse prevention interventions for women who had quit smoking due to pregnancy, or for smokers undergoing a period of enforced abstinence. We also failed to detect significant effects in trials in other smokers who had quit on their own or with a formal programme. Amongst trials recruiting smokers and evaluating the effect of additional relapse prevention components we also found no evidence of benefit in any subgroup. We did not find that providing training in skills thought to be needed for relapse avoidance reduced relapse, but most studies did not use experimental designs best suited to the

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

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.

Predictors of Postpartum Relapse to Smoking

PubMed Central

Solomon, Laura J.; Higgins, Stephen T.; Heil, Sarah H.; Badger, Gary J.; Thomas, Colleen S.; Bernstein, Ira M.

2007-01-01

Postpartum relapse is common among women who stop smoking during pregnancy. We examined predictors of postpartum relapse in 87 women who quit smoking during pregnancy, 48% of whom relapsed by six months postpartum. We also explored the circumstances surrounding their first postpartum cigarette. Multivariate analyses revealed that having more friends/family members who smoke, smoking more heavily pre-pregnancy, and having higher depression scores and less concern about weight at the end of pregnancy were associated with increased risk of relapse postpartum. Most women’s first postpartum cigarettes were unplanned, in the presence of another smoker, and while experiencing negative affect. The findings suggest targets for interventions to reduce postpartum relapse. PMID:17475418

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

Platelet-derived growth factor predicts prolonged relapse-free period in multiple sclerosis.

PubMed

Stampanoni Bassi, Mario; Iezzi, Ennio; Marfia, Girolama A; Simonelli, Ilaria; Musella, Alessandra; Mandolesi, Georgia; Fresegna, Diego; Pasqualetti, Patrizio; Furlan, Roberto; Finardi, Annamaria; Mataluni, Giorgia; Landi, Doriana; Gilio, Luana; Centonze, Diego; Buttari, Fabio

2018-04-14

In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. Our results suggest that PDGF could promote a

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

Clinical factors related to schizophrenia relapse.

PubMed

Porcelli, Stefano; Bianchini, Oriana; De Girolamo, Giovanni; Aguglia, Eugenio; Crea, Luciana; Serretti, Alessandro

2016-01-01

Relapses represent one of the main problems of schizophrenia management. This article reviews the clinical factors associated with schizophrenia relapse. A research of the last 22 years of literature data was performed. Two-hundred nineteen studies have been included. Three main groups of factors are related to relapse: factors associated with pharmacological treatment, add-on psychotherapeutic treatments and general risk factors. Overall, the absence of a maintenance therapy and treatment with first generation antipsychotics has been associated with higher risk of relapse. Further, psychotherapy add-on, particularly with cognitive behaviour therapy and psycho-education for both patients and relatives, has shown a good efficacy for reducing the relapse rate. Among general risk factors, some could be modified, such as the duration of untreated psychosis or the substance misuse, while others could not be modified as male gender or low pre-morbid level of functioning. Several classes of risk factors have been proved to be relevant in the risk of relapse. Thus, a careful assessment of the risk factors here identified should be performed in daily clinical practice in order to individualise the relapse risk for each patient and to provide a targeted treatment in high-risk subjects.

Resistance to Change and Relapse of Observing

PubMed Central

Thrailkill, Eric A; Shahan, Timothy A

2012-01-01

Four experiments examined relapse of extinguished observing behavior of pigeons using a two-component multiple schedule of observing-response procedures. In both components, unsignaled periods of variable-interval (VI) food reinforcement alternated with extinction and observing responses produced stimuli associated with the availability of the VI schedule (i.e., S+). The components differed in the rate of food arranged (Rich  = VI 30 s; Lean  =  VI 120 s). In Experiment 1, following baseline training, extinction of observing involved removal of both food and S+ deliveries, and reinstatement was examined by presenting either response-independent food or S+ deliveries. In Experiment 2, extinction involved removal of only food deliveries while observing responses continued to produce S+. Reinstatement was examined by delivering food contingent upon the first two food-key responses occurring in the presence of the S+. Experiment 3 assessed ABA renewal of observing by extinguishing food-key and observing responses in the presence of one contextual stimulus (i.e., B) and then returning to the original training context (i.e., A) during continued extinction. Experiment 4 examined resurgence by introducing food reinforcement for an alternative response during extinction, and subsequently removing that alternative source of food. Across experiments, relative resistance to extinction and relapse of observing tended to be greater in the component previously associated with the higher rate of primary reinforcement. Relapse of observing or attending to stimuli associated with primary reinforcement appears to be impacted by frequency of primary reinforcement in a manner similar to responding maintained directly by primary reinforcement. PMID:22693359

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study.

PubMed

Ellin, Fredrik; Landström, Jenny; Jerkeman, Mats; Relander, Thomas

2015-07-02

Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P = .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P = .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P = .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P = .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. © 2015 by The American Society of Hematology.

[Research and control of relapse tuberculosis cases].

PubMed

Yamagishi, Fumio; Toyota, Makoto

2009-12-01

With this symposium, we focused on the relapse of tuberculosis in Japan. Out of 19,893 tuberculosis patients registered in 2007 in Japan, 7.48% were classified as relapse cases. Relapse cases have the risk of acquired drug resistance. But we have few analyses of the proportion of relapse tuberculosis cases with standard short course regimens for six months, factors contributing to tuberculosis relapse and the proportion of drug resistance among relapse TB cases in Japan. Therefore we analyzed the relapse tuberculosis cases in two rural areas and three urban areas. We also analyzed the proportion of drug resistance among relapse cases with the data of drug susceptibility survey of Ryoken. 1. Research of relapse tuberculosis cases: Makoto TOYOTA (Kochi City Public Health Center). To clarify the relapse rate and factors contributing to tuberculosis relapse, we investigated the relapse tuberculosis cases in the municipality where the proportion of elderly tuberculosis patients was high. Out of 902 tuberculosis patients registered in Kochi City Public Health Center during 10 years, 20 pulmonary tuberculosis patients were confirmed relapse cases with initial registered records. Pretreatment cavitations, sputum culture positivity at 2 months, medical miss-management (e.g. number of doses, duration of therapy) and poor adherence were considered to be factors contributing to tuberculosis relapse. Out of 20 relapse cases, 12 cases were detected with symptoms, while only 3 cases were detected by examination in law. 2. A clinical study on relapse cases of pulmonary tuberculosis: Shuichi TAKIKAWA (National Hospital Organization Nishibeppu National Hospital). The relapse of pulmonary tuberculosis was investigated. In the cases with a treatment history before short course chemotherapy, drug resistance rate was high, and thus it needs to be cautious of drug resistance at the time of the retreatment. In the cases with a treatment history of short course chemotherapy, relapse cases

Relapse prevention and smoking cessation.

PubMed

Davis, J R; Glaros, A G

1986-01-01

A multicomponent smoking relapse prevention treatment based on Marlatt and Gordon's (1980) model of the relapse process was developed and evaluated. Behavior-analytic methods were used to develop assessment instruments, training situations, and coping responses. The prevention components were presented in the context of a basic broad-spectrum stop-smoking program, and were compared with the basic program plus discussion control, and the basic program alone. Smoking-related dependent variables generally did not differ between groups at any time from pre-treatment to 12 month follow-up. Only the subjects in the relapse prevention condition improved problem-solving and social skills needed to cope with high-risk situations. These subjects also tended to take longer to relapse and smoke fewer cigarettes at the time of relapse. Subjects above the median level of competence on measures of social skill at post-treatment remained abstinent significantly longer. Maintenance of non-smoking was found to be related to the degree of competence with which individuals deal with high-risk situations. Results are discussed in relation to models of compliance with therapeutic regimens.

Relapse prevention for addictive behaviors

PubMed Central

2011-01-01

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change. PMID:21771314

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.

Additional follow-up telephone counselling and initial smoking relapse: a longitudinal, controlled study.

PubMed

Wu, Lei; He, Yao; Jiang, Bin; Zuo, Fang; Liu, Qinghui; Zhang, Li; Zhou, Changxi

2016-04-20

Smoking cessation services can help smokers to quit; however, many smoking relapse cases occur over time. Initial relapse prevention should play an important role in achieving the goal of long-term smoking cessation. Several studies have focused on the effect of extended telephone support in relapse prevention, but the conclusions remain conflicting. From October 2008 to August 2013, a longitudinal, controlled study was performed in a large general hospital of Beijing. The smokers who sought treatment at our smoking cessation clinic were non-randomised and divided into 2 groups: face-to-face individual counselling group (FC group), and face-to-face individual counselling plus telephone follow-up counselling group (FCF group). No pharmacotherapy was offered. The timing of initial smoking relapse was compared between FC and FCF groups. Predictors of initial relapse were investigated during the first 180 days, using the Cox proportional hazards model. Of 547 eligible male smokers who volunteered to participate, 457 participants (117 in FC group and 340 in FCF group) achieved at least 24 h abstinence. The majority of the lapse episodes occurred during the first 2 weeks after the quit date. Smokers who did not receive the follow-up telephone counselling (FC group) tended to relapse to smoking earlier than those smokers who received the additional follow-up telephone counselling (FCF group), and the log-rank test was statistically significant (p=0.003). A Cox regression model showed that, in the FCF group, being married, and having a lower Fagerström test score, normal body mass index and doctor-diagnosed tobacco-related chronic diseases, were significantly independent protective predictors of smoking relapse. Within the limitations of this study, it can be concluded that additional follow-up telephone counselling might be an effective strategy in preventing relapse. Further research is still needed to confirm our findings. Published by the BMJ Publishing Group

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.

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

Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia.

PubMed

Karlsson, Lene; Forestier, Erik; Hasle, Henrik; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Norén Nyström, Ulrika; Palle, Josefine; Tierens, Anne; Zeller, Bernward; Abrahamsson, Jonas

2017-08-01

Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS 5y ) was 39 ± 4% for the whole group and 43 ± 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) ± anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse ≥1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS 5y was 61 ± 5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML. © 2017 John Wiley & Sons Ltd.

Operant models of relapse in zebrafish (Danio rerio): Resurgence, renewal, and reinstatement.

PubMed

Kuroda, Toshikazu; Mizutani, Yuto; Cançado, Carlos R X; Podlesnik, Christopher A

2017-09-29

Zebrafish are a widely used animal model in biomedical research, as an alternative to mammals, for having features such as a fully sequenced genome, high fecundity, and low-cost maintenance, but behavioral research with these fish remains scarce. The present study investigated whether zebrafish could be a new animal model for studies on the relapse of behavior (e.g., addiction and overeating) after the behavior has been extinguished. Specifically, we examined whether zebrafish would show three different types of relapse commonly studied with other species: resurgence, renewal, and reinstatement. For resurgence, a target response (i.e., approaching a sensor) was established by presenting a reinforcer (i.e., shrimp eggs) contingent upon the response in Phase 1; the target response was extinguished while introducing reinforcement for an alternative response in Phase 2; neither response produced the reinforcer in Phase 3. For renewal, a target response was established under Context A in Phase 1 and was extinguished under Context B in Phase 2; the fish were placed back in Context A in Phase 3, where extinction remained in effect. For reinstatement, a target response was established in Phase 1 and was extinguished in Phase 2; the reinforcer was presented independently of responding in Phase 3. Each type of relapse occurred in Phase 3. These results replicate and extend previous findings on relapse to a new species and suggest that zebrafish can be a useful animal model for studying the interactions of biological and environmental factors that lead to relapse. Copyright © 2017 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

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.

Determinants of Relapse Following Smoking Cessation.

ERIC Educational Resources Information Center

Shiffman, Saul M.

Although research has been conducted on who will relapse after having quit smoking in clinics, little has been done to determine the immediate precipitants of recidivism. A telephone hotline, manned by four experienced interviewers, was set up to receive calls from ex-smokers who had relapsed or who felt at high risk for relapse. A structured…

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.

Factors associated with extended treatment among tuberculosis patients at risk of relapse in California.

PubMed

Qin, F; Barry, P M; Pascopella, L

2016-03-01

California, United States. To determine the frequency of tuberculosis (TB) patients at risk for relapse who received at least 9 months of anti-tuberculosis treatment (extended treatment) and to identify factors associated with not receiving extended treatment. We analyzed characteristics of culture-confirmed pulmonary TB patients reported to the California TB Registry during 2004-2009. Patients with cavities on initial chest radiograph and delayed culture conversion (⩾70 days) were at 'high risk of relapse', and anti-tuberculosis treatment of ⩾270 days was 'extended treatment'. We used a generalized linear model to identify independent risk factors for absence of extended treatment in the high risk of relapse group. Among 5680 TB patients, 483 (8.5%) were at high risk of relapse: 372 (77%) received extended treatment but 111 (23%) did not. Factors associated with absence of extended treatment included negative sputum smears (adjusted prevalence ratio [aPR] 2.62, 95%CI 1.69-4.05), residence in three specific counties (aPR 1.71, 95%CI 1.19-2.46) and Black race (aPR 1.56, 95%CI 1.03-2.38). Nearly a quarter of TB patients at high risk of relapse did not receive extended treatment. Increased efforts are needed to ensure that all patients who may benefit from extended anti-tuberculosis treatment receive it.

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

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.

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.

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

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, Peter; Stead, Lindsay F; West, Robert; Jarvis, Martin; Hartmann-Boyce, Jamie; Lancaster, Tim

2013-08-20

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, Peter; Stead, Lindsay F; West, Robert; Jarvis, Martin; Lancaster, Tim

2009-01-21

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions were proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register in August 2008 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow up of six months. We included smokers who quit on their own, or were undergoing enforced abstinence, or who were participating in treatment programmes. We included trials that compared relapse prevention interventions to a no intervention control, or that compared a cessation programme with additional relapse prevention components to a cessation programme alone. Studies were screened and data extracted by one author and checked by a second. Disagreements were resolved by discussion or referral to a third author. Fifty-four studies met inclusion criteria, but were heterogeneous in terms of populations and interventions. We considered 36 studies that randomized abstainers separately from studies that randomized participants prior to their quit date.Looking at studies of behavioural interventions which randomised abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking due to pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or with a formal programme. Amongst trials randomising smokers prior to their quit date and evaluating the effect of additional relapse prevention components we also found no evidence of benefit of

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…

Postpartum smoking relapse and becoming a mother.

PubMed

Gaffney, Kathleen F

2006-01-01

To propose an innovative, theoretically-derived conceptual framework for studies of postpartum smoking relapse including concepts of smoking abstinence self-efficacy and becoming a mother. Presentation of an existing research paradigm followed by evidence from intervention research and studies of factors associated with postpartum smoking behavior, leading to a new approach to postpartum smoking relapse. Effectiveness of current interventions to prevent relapse is limited. Variables associated with becoming a mother are missing from studies of postpartum smoking relapse. Context-specific variables that influence a woman's progression through the stages of becoming a mother might include protective or risk factors that should be incorporated into the design of postpartum smoking relapse studies.

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.

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.

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.

Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

PubMed

Ludovini, Vienna; Bianconi, Fortunato; Siggillino, Annamaria; Piobbico, Danilo; Vannucci, Jacopo; Metro, Giulio; Chiari, Rita; Bellezza, Guido; Puma, Francesco; Della Fazia, Maria Agnese; Servillo, Giuseppe; Crinò, Lucio

2016-05-24

Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR.From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS).Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy.

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

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

PubMed

Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

2018-05-16

To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

PubMed

Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

2017-05-22

PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age

Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

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

Pan, Hubert Y.; Morani, Ajaykumar; Wang, Wei-Lien

2015-06-01

Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66more » patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of

CREBBP mutations in relapsed acute lymphoblastic leukaemia

PubMed Central

Mullighan, Charles G.; Zhang, Jinghui; Kasper, Lawryn H.; Lerach, Stephanie; Payne-Turner, Debbie; Phillips, Letha A.; Heatley, Sue L.; Holmfeldt, Linda; Collins-Underwood, J. Racquel; Ma, Jing; Buetow, Kenneth H.; Pui, Ching-Hon; Baker, Sharyn D.; Brindle, Paul K.; Downing, James R.

2010-01-01

Relapsed acute lymphoblastic leukaemia (ALL) is a leading cause of death due to disease in young people, but the biologic determinants of treatment failure remain poorly understood. Recent genome-wide profiling of structural DNA alterations in ALL have identified multiple submicroscopic somatic mutations targeting key cellular pathways1,2, and have demonstrated substantial evolution in genetic alterations from diagnosis to relapse3. However, detailed analysis of sequence mutations in ALL has not been performed. To identify novel mutations in relapsed ALL, we resequenced 300 genes in matched diagnosis and relapse samples from 23 patients with ALL. This identified 52 somatic non-synonymous mutations in 32 genes, many of which were novel, including the transcriptional coactivators CREBBP and NCOR1, the transcription factors ERG, SPI1, TCF4 and TCF7L2, components of the Ras signalling pathway, histone genes, genes involved in histone modification (CREBBP and CTCF), and genes previously shown to be targets of recurring DNA copy number alteration in ALL. Analysis of an extended cohort of 71 diagnosis-relapse cases and 270 acute leukaemia cases that did not relapse found that 18.3% of relapse cases had sequence or deletion mutations of CREBBP, which encodes the transcriptional coactivator and histone acetyltransferase (HAT) CREB-binding protein (CBP)4. The mutations were either present at diagnosis or acquired at relapse, and resulted in truncated alleles or deleterious substitutions in conserved residues of the HAT domain. Functionally, the mutations impaired histone acetylation and transcriptional regulation of CREBBP targets, including glucocorticoid responsive genes. Several mutations acquired at relapse were detected in subclones at diagnosis, suggesting that the mutations may confer resistance to therapy. These results extend the landscape of genetic alterations in leukaemia, and identify mutations targeting transcriptional and epigenetic regulation as a mechanism

A Method of Calculating Functional Independence Measure at Discharge from Functional Independence Measure Effectiveness Predicted by Multiple Regression Analysis Has a High Degree of Predictive Accuracy.

PubMed

Tokunaga, Makoto; Watanabe, Susumu; Sonoda, Shigeru

2017-09-01

Multiple linear regression analysis is often used to predict the outcome of stroke rehabilitation. However, the predictive accuracy may not be satisfactory. The objective of this study was to elucidate the predictive accuracy of a method of calculating motor Functional Independence Measure (mFIM) at discharge from mFIM effectiveness predicted by multiple regression analysis. The subjects were 505 patients with stroke who were hospitalized in a convalescent rehabilitation hospital. The formula "mFIM at discharge = mFIM effectiveness × (91 points - mFIM at admission) + mFIM at admission" was used. By including the predicted mFIM effectiveness obtained through multiple regression analysis in this formula, we obtained the predicted mFIM at discharge (A). We also used multiple regression analysis to directly predict mFIM at discharge (B). The correlation between the predicted and the measured values of mFIM at discharge was compared between A and B. The correlation coefficients were .916 for A and .878 for B. Calculating mFIM at discharge from mFIM effectiveness predicted by multiple regression analysis had a higher degree of predictive accuracy of mFIM at discharge than that directly predicted. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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.

The neuropharmacology of relapse to food seeking: methodology, main findings, and comparison with relapse to drug seeking.

PubMed

Nair, Sunila G; Adams-Deutsch, Tristan; Epstein, David H; Shaham, Yavin

2009-09-01

Relapse to old, unhealthy eating habits is a major problem in human dietary treatments. The mechanisms underlying this relapse are unknown. Surprisingly, until recently this clinical problem has not been systematically studied in animal models. Here, we review results from recent studies in which a reinstatement model (commonly used to study relapse to abused drugs) was employed to characterize the effect of pharmacological agents on relapse to food seeking induced by either food priming (non-contingent exposure to small amounts of food), cues previously associated with food, or injections of the pharmacological stressor yohimbine. We also address methodological issues related to the use of the reinstatement model to study relapse to food seeking, similarities and differences in mechanisms underlying reinstatement of food seeking versus drug seeking, and the degree to which the reinstatement procedure provides a suitable model for studying relapse in humans. We conclude by discussing implications for medication development and future research. We offer three tentative conclusions: (1)The neuronal mechanisms of food-priming- and cue-induced reinstatement are likely different from those of reinstatement induced by the pharmacological stressor yohimbine. (2)The neuronal mechanisms of reinstatement of food seeking are possibly different from those of ongoing food-reinforced operant responding. (3)The neuronal mechanisms underlying reinstatement of food seeking overlap to some degree with those of reinstatement of drug seeking.

Is Ki-67 Expression Prognostic for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast Conservation Therapy (BCT)?

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

Hafeez, Farhaan; Neboori, Hanmanth J.; Harigopal, Malini

2013-10-01

Purpose: Ki-67 is a human nuclear protein whose expression is strongly up-regulated in proliferating cells and can be used to determine the growth fraction in clonal cell populations. Although there are some data to suggest that Ki-67 overexpression may be prognostic for endpoints such as survival or postmastectomy recurrence, further elucidation of its prognostic significance is warranted. Specifically after breast conservation therapy (BCT) (defined in this setting as breast-conserving surgery and adjuvant radiation therapy), whether Ki-67 predicts for locoregional recurrence has not been investigated. The purpose of this study was to assess Ki-67 expression in a cohort of early-stage breastmore » cancer patients to determine whether a significant independent association between Ki-67 and locoregional relapse exists. Methods and Materials: Ki-67 staining was conducted on a tissue microarray of 438 patients previously treated with BCT, and expression was analyzed with clinicopathologic features and outcomes from our database. Results: Ki-67 expression was more prevalent in black patients (37% of black patients vs 17% of white patients, P<.01), younger patients (27% of patients aged ≤50 years vs 15% of patients aged >50 years, P<.01), estrogen receptor (ER)–negative tumors (25% of ER-negative tumors vs 17% of ER-positive tumors, P=.04), human epidermal growth factor receptor 2 (HER2)/neu–positive tumors (35% of HER2-positive tumors vs 18% of HER2-negative tumors, P=.01), and larger tumors (26% of T2 tumors vs 16% of T1 tumors, P=.03). On univariate/multivariate analysis, Ki-67 did not predict for overall survival (74.4% vs 72.6%), cause-specific survival (82.9% vs 82.1%), local relapse-free survival (83.6% vs 88.5%), distant metastasis-free survival (76.1% vs 81.4%), recurrence-free survival (65.5% vs 74.6%), and locoregional recurrence-free survival (81.6% vs 84.7%): P>.05 for all. Conclusions: Ki-67 appears to be a surrogate marker for aggressive disease

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.

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

Posterior Predictive Checks for Conditional Independence between Response Time and Accuracy

ERIC Educational Resources Information Center

Bolsinova, Maria; Tijmstra, Jesper

2016-01-01

Conditional independence (CI) between response time and response accuracy is a fundamental assumption of many joint models for time and accuracy used in educational measurement. In this study, posterior predictive checks (PPCs) are proposed for testing this assumption. These PPCs are based on three discrepancy measures reflecting different…

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.

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.

Relapse in opiate addicts: a behavioral analysis.

PubMed

Chaney, E F; Roszell, D K; Cummings, C

1982-01-01

Behavioral interviewing was used to study the relapse antecedents and concomitants of 38 opiate addicts on methadone maintenance. Relapse situations were categorized with regard to intra- or interpersonal determinants and implications for behavioral treatment interventions were discussed. Situations were also analyzed within an opponent process theory of motivation framework. Practical and theoretical difficulties with the study of relapse situations in substance abusing populations were highlighted.

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.

A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma

PubMed Central

Xie, Wanling; Jagannath, Sundar; Jakubowiak, Andrzej; Lonial, Sagar; Raje, Noopur S.; Alsina, Melissa; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Mazumder, Amitabha; Vesole, David H.; Kaufman, Jonathan L.; Colson, Kathleen; McKenney, Mary; Lunde, Laura E.; Feather, John; Maglio, Michelle E.; Warren, Diane; Francis, Dixil; Hideshima, Teru; Knight, Robert; Esseltine, Dixie-Lee; Mitsiades, Constantine S.; Weller, Edie; Anderson, Kenneth C.

2014-01-01

In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m2 (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209. PMID:24429336

Higher Donor Apheresis Blood Volumes Are Associated with Reduced Relapse Risk and Improved Survival in Reduced-Intensity Allogeneic Transplantations with Unrelated Donors.

PubMed

Crisalli, Lisa M; Hinkle, Joanne T; Walling, Christopher C; Sell, Mary; Frey, Noelle V; Hexner, Elizabeth O; Loren, Alison W; Luger, Selina M; Stadtmauer, Edward A; Porter, David L; Reshef, Ran

2018-06-01

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a curative option for patients with hematologic malignancies who are unable to undergo myeloablative conditioning, but its success is limited by high rates of relapse. Several studies have suggested a role for T cell doses in peripheral blood stem cell grafts in RIC HSCT. Because T cell dose is typically not known until after the collection, and apheresis blood volume is easily modifiable, we hypothesized that higher donor apheresis blood volumes would improve transplantation outcomes through an effect on graft composition. Thus, we analyzed the relationships between apheresis volume, graft composition, and transplantation outcomes in 142 consecutive patients undergoing unrelated donor allogeneic RIC HSCT. We found that apheresis volume ≥15 L was associated with a significantly decreased risk of relapse (adjusted hazard ratio [aHR], .48; 95% confidence interval [CI], .28 to .84]; P = .01) and improved relapse-free survival (aHR, .56; 95% CI, .35 to .89; P = .02) and overall survival (aHR, .55; 95% CI, .34 to .91; P = .02). A high apheresis volume was not associated with increased rates of acute or chronic graft-versus-host disease. These results demonstrate that an apheresis volume of at least 15 L is independently predictive of improved transplantation outcomes after RIC allogeneic HSCT. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pre- and post-transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia.

PubMed

Lovisa, Federica; Zecca, Marco; Rossi, Bartolomeo; Campeggio, Mimma; Magrin, Elisa; Giarin, Emanuela; Buldini, Barbara; Songia, Simona; Cazzaniga, Giovanni; Mina, Tommaso; Acquafredda, Gloria; Quarello, Paola; Locatelli, Franco; Fagioli, Franca; Basso, Giuseppe

2018-03-01

Relapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre-HSCT and during the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%. The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10 -3 and ≥1 × 10 -3 , respectively, versus 73% in MRD-negative patients (P < 0·001). This effect was maintained in different disease remissions, but low-level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post-HSCT1 and post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre-emptive immuno-therapy. © 2018 John Wiley & Sons Ltd.

Preoperative frailty assessment predicts loss of independence after vascular surgery.

PubMed

Donald, Graham W; Ghaffarian, Amir A; Isaac, Farid; Kraiss, Larry W; Griffin, Claire L; Smith, Brigitte K; Sarfati, Mark R; Beckstrom, Julie L; Brooke, Benjamin S

2018-05-14

Frailty, a clinical syndrome associated with loss of metabolic reserves, is prevalent among patients who present to vascular surgery clinics for evaluation. The Clinical Frailty Scale (CFS) is a rapid assessment method shown to be highly specific for identifying frail patients. In this study, we sought to evaluate whether the preoperative CFS score could be used to predict loss of independence after major vascular procedures. We identified all patients living independently at home who were prospectively assessed using the CFS before undergoing an elective major vascular surgery procedure (admitted for >24 hours) at an academic medical center between December 2015 and December 2017. Patient- and procedure-level clinical data were obtained from our institutional Vascular Quality Initiative registry database. The composite outcome of discharge to a nonhome location or 30-day mortality was evaluated using bivariate and multivariate regression models. A total of 134 independent patients were assessed using the CFS before they underwent elective open abdominal aortic aneurysm repair (8%), endovascular aneurysm repair (26%), thoracic endovascular aortic repair (6%), suprainguinal bypass (6%), infrainguinal bypass (16%), carotid endarterectomy (19%), or peripheral vascular intervention (20%). Among 39 (29%) individuals categorized as being frail using the CFS, there was no significant difference in age or ASA physical status compared with nonfrail patients. However, frail patients were significantly more likely to need mobility assistance after surgery (62% frail vs 22% nonfrail; P < .01) and to be discharged to a nonhome location (22% frail vs 6% nonfrail; P = .01) or to die within 30 days after surgery (8% frail vs 0% nonfrail; P < .01). Preoperative frailty was associated with a >12-fold higher risk (odds ratio, 12.1; 95% confidence interval, 2.17-66.96; P < .01) of 30-day mortality or loss of independence, independent of the vascular procedure undertaken. The CFS

Measure of functional independence dominates discharge outcome prediction after inpatient rehabilitation for stroke.

PubMed

Brown, Allen W; Therneau, Terry M; Schultz, Billie A; Niewczyk, Paulette M; Granger, Carl V

2015-04-01

Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. The sample included 148,367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission (r(2)=0.107). No important additional effect for any other variable was detected when added to this model. This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set. © 2015 American Heart Association, Inc.

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

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.

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.

Cortical relapses in multiple sclerosis.

PubMed

Puthenparampil, Marco; Poggiali, Davide; Causin, Francesco; Rolma, Giuseppe; Rinaldi, Francesca; Perini, Paola; Gallo, Paolo

2016-08-01

Multiple sclerosis (MS) is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in patients with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described. We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) patients who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke's aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms. Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS. © The Author(s), 2015.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

PubMed

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.

PubMed

Byrd, John C; Furman, Richard R; Coutre, Steven E; Flinn, Ian W; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Sharman, Jeff P; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Sukbuntherng, Juthamas; Chang, Betty Y; Clow, Fong; Hedrick, Eric; Buggy, Joseph J; James, Danelle F; O'Brien, Susan

2013-07-04

The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01105247.).

Relapse Prevention and the Five Rules of Recovery.

PubMed

Melemis, Steven M

2015-09-01

There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don't bend the rules.

Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study.

PubMed

Rea, Delphine; Henry, Guylaine; Khaznadar, Zena; Etienne, Gabriel; Guilhot, François; Nicolini, Franck; Guilhot, Joelle; Rousselot, Philippe; Huguet, Françoise; Legros, Laurence; Gardembas, Martine; Dubruille, Viviane; Guerci-Bresler, Agnès; Charbonnier, Aude; Maloisel, Frédéric; Ianotto, Jean-Christophe; Villemagne, Bruno; Mahon, François-Xavier; Moins-Teisserenc, Hélène; Dulphy, Nicolas; Toubert, Antoine

2017-08-01

Despite persistence of leukemic stem cells, patients with chronic myeloid leukemia who achieve and maintain deep molecular responses may successfully stop the tyrosine kinase inhibitor imatinib. However, questions remain unanswered regarding the biological basis of molecular relapse after imatinib cessation. In IMMUNOSTIM, we monitored 51 patients from the French Stop IMatinib trial for peripheral blood T cells and natural killer cells. Molecular relapse-free survival at 24 months was 45.1% (95% CI: 31.44%-58.75%). At the time of imatinib discontinuation, non-relapsing patients had significantly higher numbers of natural killer cells of the cytotoxic CD56 dim subset than had relapsing patients, while CD56 bright natural killer cells, T cells and their subsets did not differ significantly. Furthermore, the CD56 dim natural killer-cell count was an independent prognostic factor of molecular-relapse free survival in a multivariate analysis. However, expression of natural killer-cell activating receptors, BCR-ABL1 + leukemia cell line K562-specific degranulation and cytokine-induced interferon-gamma secretion were decreased in non-relapsing and relapsing patients as compared with healthy individuals. After imatinib cessation, the natural killer-cell count increased significantly and stayed higher in non-relapsing patients than in relapsing patients, while receptor expression and functional properties remained unchanged. Altogether, our results suggest that natural killer cells may play a role in controlling leukemia-initiating cells at the origin of relapse after imatinib cessation, provided that these cells are numerous enough to compensate for their functional defects. Further research will decipher mechanisms underlying functional differences between natural killer cells from patients and healthy individuals and evaluate the potential interest of immunostimulatory approaches in tyrosine kinase inhibitor discontinuation strategies. (ClinicalTrial.gov Identifier NCT

Marital status independently predicts testis cancer survival--an analysis of the SEER database.

PubMed

Abern, Michael R; Dude, Annie M; Coogan, Christopher L

2012-01-01

Previous reports have shown that married men with malignancies have improved 10-year survival over unmarried men. We sought to investigate the effect of marital status on 10-year survival in a U.S. population-based cohort of men with testis cancer. We examined 30,789 cases of testis cancer reported to the Surveillance, Epidemiology, and End Results (SEER 17) database between 1973 and 2005. All staging were converted to the 1997 AJCC TNM system. Patients less than 18 years of age at time of diagnosis were excluded. A subgroup analysis of patients with stages I or II non-seminomatous germ cell tumors (NSGCT) was performed. Univariate analysis using t-tests and χ(2) tests compared characteristics of patients separated by marital status. Multivariate analysis was performed using a Cox proportional hazard model to generate Kaplan-Meier survival curves, with all-cause and cancer-specific mortality as the primary endpoints. 20,245 cases met the inclusion criteria. Married men were more likely to be older (38.9 vs. 31.4 years), Caucasian (94.4% vs. 92.1%), stage I (73.1% vs. 61.4%), and have seminoma as the tumor histology (57.3% vs. 43.4%). On multivariate analysis, married status (HR 0.58, P < 0.001) and Caucasian race (HR 0.66, P < 0.001) independently predicted improved overall survival, while increased age (HR 1.05, P < 0.001), increased stage (HR 1.53-6.59, P < 0.001), and lymphoid (HR 4.05, P < 0.001), or NSGCT (HR 1.89, P < 0.001) histology independently predicted death. Similarly, on multivariate analysis, married status (HR 0.60, P < 0.001) and Caucasian race (HR 0.57, P < 0.001) independently predicted improved testis cancer-specific survival, while increased age (HR 1.03, P < 0.001), increased stage (HR 2.51-15.67, P < 0.001), and NSGCT (HR 2.54, P < 0.001) histology independently predicted testis cancer-specific death. A subgroup analysis of men with stages I or II NSGCT revealed similar predictors of all-cause survival as the overall cohort, with

Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

PubMed

Hoffmann, Sarah; Harms, Hendrik; Ulm, Lena; Nabavi, Darius G; Mackert, Bruno-Marcel; Schmehl, Ingo; Jungehulsing, Gerhard J; Montaner, Joan; Bustamante, Alejandro; Hermans, Marcella; Hamilton, Frank; Göhler, Jos; Malzahn, Uwe; Malsch, Carolin; Heuschmann, Peter U; Meisel, Christian; Meisel, Andreas

2017-12-01

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Preventing Relapse to Cigarette Smoking by Behavioral Skill Training.

ERIC Educational Resources Information Center

Hall, Sharon M.; And Others

1984-01-01

Crossed two relapse prevention conditions (skills training-vs-discussion control) with two levels of aversive smoking in volunteer subjects (N=123). Results indicated that relapse-prevention skill training did prevent relapse among cigarette smokers. Lighter smokers were more favorably influenced. (LLL)

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

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

Rimner, Andreas; Lovie, Shona; Hsu, Meier

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followedmore » by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.« less

Ways of problem solving as predictors of relapse in alcohol dependent male inpatients.

PubMed

Demirbas, Hatice; Ilhan, Inci Ozgur; Dogan, Yildirim Beyatli

2012-01-01

The purpose of this study was to identify how remitters and relapsers view their everyday problem solving strategies. A total of 128 male alcohol dependent male inpatients who were hospitalized at the Ankara University Psychiatry Clinic, Alcohol and Substance Abuse Treatment Unit were recruited for the study. Subjects demographic status and alcohol use histories were assessed by a self-report questionnaire. Also, patients were evaluated with The Coopersmith Self-esteem Inventory (CSI), The Spielberger State-Trait Anxiety Scale (STAI-I-II), and The Problem Solving Inventory (PSI). Patients were followed for six months with monthly intervals after hospital discharge. Drinking status was assessed in terms of abstinence and relapse. Data were assessed with Student t-test, and univariate and multivariate analyses. In the logistic regression analysis, age, marital status, employment status and PSI subscores were taken as the independent variables and drinking state at the end of six months as the dependent variable. There were significant differences in reflective and avoidant styles, and monitoring style of problem solving between abstainers and relapses. It was found that subjects who perceived their problem solving style as less avoidant and less reflective were at greater risk to relapse. The findings demonstrated that active engagement in problem solving like utilizing avoidant and reflective styles of problem solving enhances abstinence. In treatment, expanding the behavior repertoire and increasing the variety of ways of problem solving ways that can be utilized in daily life should be one of the major goals of the treatment program. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determinants of Relapse for Polysubstance Abusers.

ERIC Educational Resources Information Center

Schonfeld, Lawrence; And Others

It has been estimated that as many as 75% of individuals treated for substance abuse relapse within 90 days after completion of treatment. Studies of relapse have typically defined the problem as a return to the specific substance for which the individual was originally treated. Because multiple substance appears to be common, this study examined…

Relapse Prevention and the Five Rules of Recovery

PubMed Central

Melemis, Steven M.

2015-01-01

There are four main ideas in relapse prevention. First, relapse is a gradual process with distinct stages. The goal of treatment is to help individuals recognize the early stages, in which the chances of success are greatest. Second, recovery is a process of personal growth with developmental milestones. Each stage of recovery has its own risks of relapse. Third, the main tools of relapse prevention are cognitive therapy and mind-body relaxation, which are used to develop healthy coping skills. Fourth, most relapses can be explained in terms of a few basic rules. Educating clients in these rules can help them focus on what is important: 1) change your life (recovery involves creating a new life where it is easier to not use); 2) be completely honest; 3) ask for help; 4) practice self-care; and 5) don’t bend the rules. PMID:26339217

Relative Efficacy of Mindfulness-Based Relapse Prevention, Standard Relapse Prevention, and Treatment as Usual for Substance Use Disorders

PubMed Central

Bowen, Sarah; Witkiewitz, Katie; Clifasefi, Seema L.; Grow, Joel; Chawla, Neharika; Hsu, Sharon H.; Carroll, Haley A.; Harrop, Erin; Collins, Susan E.; Lustyk, M. Kathleen; Larimer, Mary E.

2015-01-01

IMPORTANCE Relapse is highly prevalent following substance abuse treatments, highlighting the need for improved aftercare interventions. Mindfulness-based relapse prevention (MBRP), a group-based psychosocial aftercare, integrates evidence-based practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches. OBJECTIVE To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual (TAU [12-step programming and psychoeducation]) during a 12-month follow-up period. DESIGN, SETTING, AND PARTICIPANTS Between October 2009 and July 2012, a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private, nonprofit treatment facility were randomized to MBRP, RP, or TAU aftercare and monitored for 12 months. Participants medically cleared for continuing care were aged 18 to 70 years; 71.5% were male and 42.1% were of ethnic/racial minority. INTERVENTIONS Participants were randomly assigned to 8 weekly group sessions of MBRP, cognitive-behavioral RP, or TAU. MAIN OUTCOMES AND MEASURES Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days. Variables were assessed at baseline and at 3-, 6-, and 12-month follow-up points. Measures used included self-report of relapse and urinalysis drug and alcohol screenings. RESULTS Compared with TAU, participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and, among those who used substances, significantly fewer days of substance use and heavy drinking at the 6-month follow-up. Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use. At the 12-month follow-up, MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU. CONCLUSIONS AND RELEVANCE For individuals in aftercare

Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma

PubMed Central

Richardson, Paul G.; Weller, Edie; Jagannath, Sundar; Avigan, David E.; Alsina, Melissa; Schlossman, Robert L.; Mazumder, Amitabha; Munshi, Nikhil C.; Ghobrial, Irene M.; Doss, Deborah; Warren, Diane L.; Lunde, Laura E.; McKenney, Mary; Delaney, Carol; Mitsiades, Constantine S.; Hideshima, Teru; Dalton, William; Knight, Robert; Esseltine, Dixie-Lee; Anderson, Kenneth C.

2009-01-01

Purpose Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM. Patients and Methods Patients received lenalidomide 5, 10, or 15 mg/d on days 1 through 14 and received bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20mg or 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) was added for progressive disease after two cycles. Primary end points were safety and MTD determination. Results Thirty-eight patients were enrolled across six dose cohorts. The MTD was lenalidomide 15 mg/d plus bortezomib 1.0 mg/m2. Dose-limiting toxicities (n = 1 for each) were grade 3 hyponatremia and herpes zoster reactivation and grade 4 neutropenia. The most common treatment-related, grades 3 to 4 toxicities included reversible neutropenia, thrombocytopenia, anemia, and leukopenia. Among 36 response-evaluable patients, 61% (90% CI, 46% to 75%) achieved minimal response or better. Among 18 patients who had dexamethasone added, 83% (90% CI, 62% to 95%) achieved stable disease or better. Median overall survival was 37 months. Conclusion Lenalidomide plus bortezomib was well tolerated and showed promising activity with durable responses in patients with relapsed and relapsed/refractory MM, including patients previously treated with lenalidomide, bortezomib, and/or thalidomide. The combination of lenalidomide, bortezomib, and dexamethasone is being investigated in a phase II study in this setting and in newly diagnosed MM. PMID:19786667

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.

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Survival After Relapse of Medulloblastoma.

PubMed

Koschmann, Carl; Bloom, Karina; Upadhyaya, Santhosh; Geyer, J Russell; Leary, Sarah E S

2016-05-01

Survival after recurrence of medulloblastoma has not been reported in an unselected cohort of patients in the contemporary era. We reviewed 55 patients diagnosed with medulloblastoma between 2000 and 2010, and treated at Seattle Children's Hospital to evaluate patterns of relapse treatment and survival. Fourteen of 47 patients (30%) over the age of 3 experienced recurrent or progressive medulloblastoma after standard therapy. The median time from diagnosis to recurrence was 18.0 months (range, 3.6 to 62.6 mo), and site of recurrence was metastatic in 86%. The median survival after relapse was 10.3 months (range, 1.3 to 80.5 mo); 3-year survival after relapse was 18%. There were trend associations between longer survival and having received additional chemotherapy (median survival 12.8 vs. 1.3 mo, P=0.16) and radiation therapy (15.4 vs. 5.9 mo, P=0.20). Isolated local relapse was significantly associated with shorter survival (1.3 vs. 12.8 mo, P=0.009). Recurrence of medulloblastoma is more likely to be metastatic than reported in previous eras. Within the limits of our small sample, our data suggest a potential survival benefit from retreatment with cytotoxic chemotherapy and radiation even in heavily pretreated patients. This report serves as a baseline against which to evaluate novel therapy combinations.

Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy.

PubMed

Santoni, Matteo; Buti, Sebastiano; Conti, Alessandro; Porta, Camillo; Procopio, Giuseppe; Sternberg, Cora N; Bracarda, Sergio; Basso, Umberto; De Giorgi, Ugo; Rizzo, Mimma; Derosa, Lisa; Ortega, Cinzia; Massari, Francesco; Milella, Michele; Bersanelli, Melissa; Cerbone, Linda; Muzzonigro, Giovanni; Burattini, Luciano; Montironi, Rodolfo; Santini, Daniele; Cascinu, Stefano

2015-12-01

We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3-NA) in group B (p < 0.001). The median progression-free survival (PFS) was 15.8 months in group A and 25.1 months in group B (p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation.

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.

Burden of a multiple sclerosis relapse: the patient's perspective.

PubMed

Oleen-Burkey, Merrikay; Castelli-Haley, Jane; Lage, Maureen J; Johnson, Kenneth P

2012-01-01

Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the

Islet oxygen consumption rate (OCR) dose predicts insulin independence for first clinical islet allotransplants

PubMed Central

Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK

2014-01-01

Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089

Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

PubMed

Peled, Jonathan U; Devlin, Sean M; Staffas, Anna; Lumish, Melissa; Khanin, Raya; Littmann, Eric R; Ling, Lilan; Kosuri, Satyajit; Maloy, Molly; Slingerland, John B; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Shono, Yusuke; Slingerland, Ann E; Docampo, Melissa D; Sung, Anthony D; Weber, Daniela; Alousi, Amin M; Gyurkocza, Boglarka; Ponce, Doris M; Barker, Juliet N; Perales, Miguel-Angel; Giralt, Sergio A; Taur, Ying; Pamer, Eric G; Jenq, Robert R; van den Brink, Marcel R M

2017-05-20

Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

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.

Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

PubMed

Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

2018-02-01

Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p < 0.0001). Five patients in the relapsed group also had a total of 10 relapses after B-cell recovery; their median time from B-cell recovery to initial relapse was significantly shorter than in the non-relapsed group (31 vs. 161 days, p = 0.014). Number of relapses before rituximab, history of steroid resistance, onset age, previous treatment, time to ceasing steroids after rituximab, and duration of B-cell depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

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.

miR-185 is an independent prognosis factor and suppresses tumor metastasis in gastric cancer.

PubMed

Tan, Zhiqin; Jiang, Hao; Wu, Youhua; Xie, Liming; Dai, Wenxiang; Tang, Hailin; Tang, Sanyuan

2014-01-01

miR-185 has been identified as an important factor in several cancers such as breast cancer, ovarial cancer, and prostate cancer. However, its effect and prognostic value in gastric cancer are still poorly known. In this study, we found that the expression levels of miR-185 were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Moreover, miR-185 might independently predict OS and RFS in gastric cancer. We further found that upregulation of miR-185 inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. Taken together, our findings demonstrate that the miR-185 is important for gastric cancer initiation and progression and holds promise as a prognostic biomarker to predict survival and relapse in gastric cancer. It is also a potential therapeutic tool to improve clinical outcomes in the above disease.

The entanglement between relapse and posttreatment criminal justice involvement.

PubMed

Kopak, Albert M; Haugh, Stephanie; Hoffmann, Norman G

2016-09-01

Research has established a connection between substance use and criminal activity, but much less is known about the association between posttreatment relapse and related contact with the criminal justice system. The current study was designed to elucidate this relationship by examining the long-term effects of relapse on arrest. The study also investigated the probability of relapse into substance use as it followed an arrest. Data from 5,822 adults who participated in the Comprehensive Assessment and Treatment Outcome Research (CATOR) system were analyzed. This prospective longitudinal research design included 0-6, 6-12, 12-18, and 18-24 month follow-up data. A series of logistic regression analyses indicated that relapse was associated with posttreatment arrest within the observed follow-up period, but did not significantly influence the likelihood of arrest in future follow-up periods. In comparison, posttreatment arrest in the 6-12 month follow-up period had lasting effects for relapse to substance use in the 12-18 and 18-24 month periods. Arrest in the 0-6 month posttreatment period was also associated with increased risk for relapse in the 18-24 month period. Given the evidence that demonstrated within follow-up period associations between relapse and arrest, relapse prevention is critical to preventing contact with the criminal justice system. In addition, the lasting impact of an arrest must be mitigated to maintain posttreatment recovery from substance use for adults who come into contact with the criminal justice system.

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.

Could Biomarkers of Bone, Cartilage or Synovium Turnover Be Used for Relapse Prediction in Rheumatoid Arthritis Patients?

PubMed Central

Dénarié, Delphine; Constant, Elodie; Thomas, Thierry

2014-01-01

Objective. The aim of this review is to clarify the usefulness of bone, cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA) therapy in remission. Synovial Biomarkers. High MMP-3 levels are associated with joint progression in RA patients, but there is no data about their utility in clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium, but more studies are required. Cartilage Biomarkers. Unbalance between cartilage break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker (PIIANP) was described. This unbalance is also associated with joint destruction and prognosis of destruction. No data are available on patients in remission. Bone Biomarkers. RA activity is correlated with an increase of bone resorption markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone resorption. There is no study about bone marker utility in remission. Conclusion. Biomarkers seem to correlate with RA activity and progression. They also could be used to manage RA therapies, but we need more data on RA remission to predict relapse. PMID:24744505

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

PubMed Central

Byrd, John C.; Furman, Richard R.; Coutre, Steven E.; Flinn, Ian W.; Burger, Jan A.; Blum, Kristie A.; Grant, Barbara; Sharman, Jeff P.; Coleman, Morton; Wierda, William G.; Jones, Jeffrey A.; Zhao, Weiqiang; Heerema, Nyla A.; Johnson, Amy J.; Sukbuntherng, Juthamas; Chang, Betty Y.; Clow, Fong; Hedrick, Eric; Buggy, Joseph J.; James, Danelle F.; O'Brien, Susan

2013-01-01

BACKGROUND The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell–receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. METHODS We conducted a phase 1b–2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. RESULTS Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The overall response rate was the same in the group that received 420 mg and the group that received 840 mg (71%), and an additional 20% and 15% of patients in the respective groups had a partial response with lymphocytosis. The response was independent of clinical and genomic risk factors present before treatment, including advanced-stage disease, the number of previous therapies, and the 17p13.1 deletion. At 26 months, the estimated progression-free survival rate was 75% and the rate of overall survival was 83%. CONCLUSIONS Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01105247.) PMID:23782158

Prevalence and Serological Diagnosis of Relapse in Paracoccidioidomycosis Patients

PubMed Central

Sylvestre, Tatiane Fernanda; Silva, Luciane Regina Franciscone; Cavalcante, Ricardo de Souza; Moris, Daniela Vanessa; Venturini, James; Vicentini, Adriana Pardini; de Carvalho, Lídia Raquel; Mendes, Rinaldo Poncio

2014-01-01

A review of 400 clinical records of paracoccidioidomycosis (PCM) patients, 93 with the acute/subacute (AF) and 307 with the chronic form (CF), attended from 1977 to 2011, selected as to the schedule of release for study by the Office of Medical Records at the University Hospital of the Faculdade de Medicina de Botucatu – São Paulo State University – UNESP, was performed to detect cases in relapse. The control of cure was performed by clinical and serological evaluation using the double agar gel immunodiffusion test (DID). In the diagnosis of relapse, DID, enzyme-linked immunosorbent assay (ELISA) and immunoblotting assay (IBgp70 and IBgp43) were evaluated. Out of 400 patients, 21 (5.2%) went through relapse, 18 of them were male and 3 were female, 6∶1 male/female ratio. Out of the 21 patients in relapse, 15 (4.8%) showed the CF, and 6 (6.4%) the AF (p>0.05). The sensitivity of DID and ELISA before treatment was the same (76.1%). DID presented higher sensitivity in pre-treatment (80%) than at relapse (45%; p = 0.017), while ELISA showed the same sensitivity (80% vs 65%; p = 0.125). The serological methods for identifying PCM patients in relapse showed low rates of sensitivity, from 12.5% in IBgp70 to 65.0% in IBgp43 identification and 68.8% in ELISA. The sensitivity of ELISA in diagnosing PCM relapse showed a strong tendency to be higher than DID (p = 0.06) and is equal to IBgp43 (p = 0.11). In sum, prevalence of relapse was not high in PCM patients whose treatment duration was based on immunological parameters. However, the used methods for serological diagnosis present low sensitivity. While more accurate serological methods are not available, we pay special attention to the mycological and histopathological diagnosis of PCM relapse. Hence, direct mycological, cytopathological, and histopathological examinations and isolation in culture for P. brasiliensis must be appropriately and routinely performed when the hypothesis of relapse is

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

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.

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

Preventing Adolescent Relapse: Concepts, Theories and Techniques.

ERIC Educational Resources Information Center

Mishra, Shitala P.; Ressler, Robert A.

This chapter discusses adolescent drug abuse relapse prevention. It presents the following four conclusions regarding the efficacy of prevention programs. First, more controlled studies are needed to evaluate the long-term effectiveness of relapse prevention strategies with adolescents in reducing factors such as cravings and increasing their…

Relapse antecedents for methamphetamine use and related factors in Taiwanese adolescents.

PubMed

Yen, Cheng-Fang; Chang, Yu-Ping

2005-02-01

The purpose of the present study was to identify the relapse antecedents for methamphetamine (MAMP) use in Taiwanese youth, and to examine the relationships between attribution of these antecedents, demographic variables, psychiatric disorders, characteristics of MAMP use, attitudes toward MAMP use, and personality. A total of 60 Taiwanese adolescents who had previously experienced MAMP relapse were studied. Their relapse antecedents for MAMP use were evaluated using the Questionnaire for Relapse Antecedents of Methamphetamine Use. Their psychiatric disorders were also assessed. The relationships among the relapse antecedents of MAMP use, demographic variables, MAMP-use characteristics, psychiatric disorders, attitudes toward MAMP use and personality were analyzed. The results of the analysis reveal that social pressure to use MAMP was the leading antecedent of relapse. Social adaptation, emotional stability, and education level were the factors that influenced adolescents' attributions of relapse antecedents for MAMP use. However, psychiatric disorder status and attitudes toward MAMP use were not related to any of the relapse antecedents. The results indicate that multiple factors influenced adolescents' attributions of relapse antecedents for MAMP use, and may serve as a basis for construction of models for teaching adolescents to manage the antecedents and reduce the risk of relapse of MAMP use.

Smoking relapse situations among a community-recruited sample of Spanish daily smokers.

PubMed

Piñeiro, Bárbara; López-Durán, Ana; Martínez-Vispo, Carmela; Fernández Del Río, Elena; Martínez, Úrsula; Rodríguez-Cano, Rubén; Míguez, M Carmen; Becoña, Elisardo

2017-12-01

Relapse is a common factor within the behavior change process. However, there is scarce and limited knowledge of smoking relapse situations in population-based samples. The aim of this study was to identify smoking relapse situations among a sample of Spanish relapsers from the general population. A sample of 775 relapsers was recruited among the general population using a snowball method. Participants completed a survey including sociodemographic, smoking-related and psychopathology variables. Smoking relapse situations were identified through specific questions assessing different aspects related to the last relapse episode. The majority of smoking relapse situations were attributed to positive affect (36.6%) and negative affect (34.3%), followed by lack of control (10.1%), smoking habit (6.7%), craving or nicotine withdrawal (6.3%), and social pressure (5.9%). Being unemployed and having a mental disorder in the past increased the likelihood of relapse in situations of negative affect. Being single and having quit smoking to save money were associated with an increased likelihood of relapse in situations of positive affect. Affect plays a significant role in smoking relapse among a community sample of unassisted Spanish smokers. Relapse may be much more of an affective and situational process than a habit, physiological or social pressure. Findings from this study may help develop tailored community smoking relapse prevention strategies or programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Independent Factors for Prediction of Poor Outcomes in Patients with Febrile Neutropenia

PubMed Central

Günalp, Müge; Koyunoğlu, Merve; Gürler, Serdar; Koca, Ayça; Yeşilkaya, İlker; Öner, Emre; Akkaş, Meltem; Aksu, Nalan Metin; Demirkan, Arda; Polat, Onur; Elhan, Atilla Halil

2014-01-01

Background Febrile neutropenia (FN) is a life-threatening condition that requires urgent management in the emergency department (ED). Recent progress in the treatment of neutropenic fever has underscored the importance of risk stratification. In this study, we aimed to determine independent factors for prediction of poor outcomes in patients with FN. Material/Methods We retrospectively evaluated 200 chemotherapy-induced febrile neutropenic patients who visited the ED. Upon arrival at the ED, clinical data, including sex, age, vital signs, underlying systemic diseases, laboratory test results, estimated GFR, blood cultures, CRP, radiologic examinations, and Multinational Association of Supportive Care in Cancer (MASCC) score of all febrile neutropenic patients were obtained. Outcomes were categorized as “poor” if serious complications during hospitalization, including death, occurred. Results The platelet count <50 000 cells/mm3 (OR 3.90, 95% CI 1.62–9.43), pulmonary infiltration (OR 3.45, 95% CI 1.48–8.07), hypoproteinemia <6 g/dl (OR 3.30, 95% CI 1.27–8.56), respiratory rate >24/min (OR 8.75, 95% CI 2.18–35.13), and MASCC score <21 (OR 9.20, 95% CI 3.98–21.26) were determined as independent risk factors for the prediction of death. The platelet count <50 000 cells/mm3 (OR 3.93, 95% CI 1.42–10.92), serum CRP >50 mg/dl (OR 3.80, 95% CI 1.68–8.61), hypoproteinemia (OR 7.81, 95% CI 3.43–17.78), eGFR ≤90 ML/min/1.73 m2 (OR 3.06, 95% CI 1.13–8.26), and MASCC score <21 (OR 3.45, 95% CI 1.53–7.79) were determined as independent risk factors for the prediction of poor clinical outcomes of FN patients. Platelet count, protein level, respiratory rate, pulmonary infiltration, CRP, MASCC score, and eGFR were shown to have a significant association with outcome. Conclusions The results of our study may help emergency medicine physicians to prevent serious complications with proper use of simple independent risk factors besides MASCC score. PMID

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

Understanding Recovery Barriers: Youth Perceptions About Substance Use Relapse

PubMed Central

Gonzales, Rachel; Anglin, M. Douglas; Beattie, Rebecca; Ong, Chris Angelo; Glik, Deborah C.

2014-01-01

Objective To qualitatively explore how treatment-involved youth retrospectively contextualize relapse from substance use. Methods Fourteen focus groups were conducted with 118 youth (78.3% male; 66.1% Latino) enrolled in participating substance abuse treatment programs (4 young adult and 10 adolescent) throughout Los Angeles County. Transcripts were analyzed for relapse perception themes. Results Dominant relapse themes include emotional reasons (90%), life stressors (85%), cognitive factors (75%), socialization processes (65%), and environmental issues (55%). Conclusions Youth perceptions about relapse during treatment should be used to better inform clinical approaches and shape early-intervention recovery agendas for substance-abusing youth. PMID:22584088

Observational attachment theory-based parenting measures predict children's attachment narratives independently from social learning theory-based measures.

PubMed

Matias, Carla; O'Connor, Thomas G; Futh, Annabel; Scott, Stephen

2014-01-01

Conceptually and methodologically distinct models exist for assessing quality of parent-child relationships, but few studies contrast competing models or assess their overlap in predicting developmental outcomes. Using observational methodology, the current study examined the distinctiveness of attachment theory-based and social learning theory-based measures of parenting in predicting two key measures of child adjustment: security of attachment narratives and social acceptance in peer nominations. A total of 113 5-6-year-old children from ethnically diverse families participated. Parent-child relationships were rated using standard paradigms. Measures derived from attachment theory included sensitive responding and mutuality; measures derived from social learning theory included positive attending, directives, and criticism. Child outcomes were independently-rated attachment narrative representations and peer nominations. Results indicated that Attachment theory-based and Social Learning theory-based measures were modestly correlated; nonetheless, parent-child mutuality predicted secure child attachment narratives independently of social learning theory-based measures; in contrast, criticism predicted peer-nominated fighting independently of attachment theory-based measures. In young children, there is some evidence that attachment theory-based measures may be particularly predictive of attachment narratives; however, no single model of measuring parent-child relationships is likely to best predict multiple developmental outcomes. Assessment in research and applied settings may benefit from integration of different theoretical and methodological paradigms.

Preventing relapse after incentivized choice treatment: A laboratory model.

PubMed

Bouton, Mark E; Thrailkill, Eric A; Bergeria, Cecilia L; Davis, Danielle R

2017-08-01

Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1. Experiment 1 found that the strength of R1 during relapse testing was not different from that seen in a no treatment control. Experiment 2 found that relapse could nevertheless be reduced by presenting reinforcers not contingent on responding during the test. Either the reinforcer for R1 or the reinforcer for R2 (which were qualitatively different types of food pellets) were effective. The experiments introduce a laboratory method for studying relapse and how to prevent it after contingency management treatments, and suggest at least one treatment that discourages relapse. The incentivized choice paradigm differs from other models of relapse of operant behavior (e.g., resurgence, renewal, reinstatement) in that it does not focus on the return of behaviors that are inhibited by extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

Relapse Model among Iranian Drug Users: A Qualitative Study.

PubMed

Jalali, Amir; Seyedfatemi, Naiemeh; Peyrovi, Hamid

2015-01-01

Relapse is a common problem in drug user's rehabilitation program and reported in all over the country. An in-depth study on patients' experiences can be used for exploring the relapse process among drug users. Therefore, this study suggests a model for relapse process among Iranian drug users. In this qualitative study with grounded theory approach, 22 participants with rich information about the phenomenon under the study were selected using purposive, snowball and theoretical sampling methods. After obtaining the informed consent, data were collected based on face-to-face, in-depth, semi-structured interviews. All interviews were analyzed in three stages of axial, selective and open coding methods. Nine main categories emerged, including avoiding of drugs, concerns about being accepted, family atmosphere, social conditions, mental challenge, self-management, self-deception, use and remorse and a main category, feeling of loss as the core variable. Mental challenge has two subcategories, evoking pleasure and craving. Relapse model is a dynamic and systematic process including from cycles of drug avoidance to remorse with a core variable as feeling of loss.  Relapse process is a dynamic and systematic process that needs an effective control. Determining a relapse model as a clear process could be helpful in clinical sessions. RESULTS of this research have depicted relapse process among Iranian drugs user by conceptual model.

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

Spirituality predicts outcome independently of expectancy following flower essence self-treatment.

PubMed

Hyland, Michael E; Geraghty, Adam W A; Joy, Oliver E T; Turner, Scott I

2006-01-01

The aim of this study was to determine whether absorption and spirituality predict the placebo response independently of expectancy. This was an open study of self-treatment with self-selected Bach flower essences. Participants' expectancy of the effect of flower essences, attitudes to complementary medicine, holistic health beliefs, absorption, and spirituality were measured prior to treatment. One month after the start of treatment, participants responded to an e-mail enquiry about symptom change using a single seven-point change scale. One hundred sixteen participants (97 university undergraduates and 19 staff) completed all assessments. Spirituality and absorption together predicted additional variance compared with a cluster of expectancy measures comprising expectancy, attitude to complementary medicine, and holistic beliefs (increment in R(2)=.042, P=.032), and spirituality alone (but not absorption alone) predicted more additional variance than did the expectancy cluster (increment in R(2)=.043, P=.014). Our data are inconsistent with conventional explanations for the placebo effect. The mechanism underlying the placebo response is not fully understood.

Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil

PubMed Central

2012-01-01

Background Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions. Methods An observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence. Results Twenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses. Conclusions A known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines. PMID:22839416

Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

PubMed Central

Giusti, Delphine; Gatouillat, Grégory; Le Jan, Sébastien; Plée, Julie; Bernard, Philippe; Antonicelli, Frank; Pham, Bach-Nga

2018-01-01

Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P < 0.01), independently of mucosal involvement. Those 10 relapsing BP patients were also characterized by a sustained high concentration of anti-BP180 AAb, whereas the serum anti-BP230 AAb concentrations did not vary in BP patients with relapse according to the presence of anti-type VII collagen AAbs. Thus, our study showed that anti-type VII collagen along with anti-BP180 AAbs detection stratified BP patients at time of relapse, illustrating a still dysregulated immune response that could reflect a potential epitope spreading mechanism in those BP patients. PMID:29619029

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer.

PubMed

Morimoto, J; Tanaka, H; Ohira, M; Kubo, N; Muguruma, K; Sakurai, K; Yamashita, Y; Maeda, K; Sawada, T; Hirakawa, K

2014-01-01

Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin-eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two-field dissection and 5201 from three-field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N-status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node-negative converted to node-positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total

Association Between Level of Hepatitis B Surface Antigen and Relapse After Entecavir Therapy for Chronic Hepatitis B Virus Infection.

PubMed

Chen, Chien-Hung; Hung, Chao-Hung; Hu, Tsung-Hui; Wang, Jing-Houng; Lu, Sheng-Nan; Su, Pei-Fang; Lee, Chuan-Mo

2015-11-01

We investigated the rate of relapse of hepatitis B virus (HBV) infection after entecavir therapy for chronic hepatitis B and the association between level of hepatitis B surface antigen (HBsAg) and relapse. In a retrospective study, we analyzed data from 252 patients with chronic HBV infection who were treated with entecavir and met the Asian Pacific Association for the Study of the Liver treatment stopping rules (mean time, 164 ± 45 weeks) from January 2007 through June 2011 in Taiwan. Eighty-three were hepatitis B e antigen (HBeAg)-positive, and 169 were HBeAg-negative. Patients had regular post-treatment follow-up examinations for at least 12 months. Virologic relapse was defined on the basis of serum HBV DNA >2000 IU/mL after entecavir therapy. Clinical relapse was defined as a level of alanine aminotransferase > 2-fold the upper limit of normal and HBV DNA > 2000 IU/mL. Two years after therapy ended, 42% of HBeAg-positive patients had a virologic relapse, and 37.6% had a clinical relapse; 3 years after therapy ended, these rates were 64.3% and 51.6% for HBeAg-negative patients, respectively. On the basis of Cox regression analysis, factors independently associated with virologic and clinical relapse included old age, HBV genotype C, and higher baseline levels of HBsAg for HBeAg-positive patients and old age and higher end-of-treatment levels of HBsAg for HBeAg-negative patients. In HBeAg-positive patients, risk of HBV relapse increased with age ≥ 40 years and HBsAg level ≥ 1000 IU/mL at baseline (P < .001). In HBeAg-negative patients, the combination of age (< 55 years) and HBsAg level (< 150 IU/mL) at the end of treatment was associated with a lower rate of virologic relapse (4.5% of HBeAg-negative patients had viral relapse at year 3). The decrease in level of HBsAg from month 12 of treatment until the end of treatment was greater in patients who did lose HBsAg after entecavir therapy compared with those who did not. The combination of age and level of

Relapsing Fevers: Neglected Tick-Borne Diseases

PubMed Central

Talagrand-Reboul, Emilie; Boyer, Pierre H.; Bergström, Sven; Vial, Laurence; Boulanger, Nathalie

2018-01-01

Relapsing fever still remains a neglected disease and little is known on its reservoir, tick vector and physiopathology in the vertebrate host. The disease occurs in temperate as well as tropical countries. Relapsing fever borreliae are spirochaetes, members of the Borreliaceae family which also contain Lyme disease spirochaetes. They are mainly transmitted by Ornithodoros soft ticks, but some species are vectored by ixodid ticks. Traditionally a Borrelia species is associated with a specific vector in a particular geographical area. However, new species are regularly described, and taxonomical uncertainties deserve further investigations to better understand Borrelia vector/host adaptation. The medical importance of Borrelia miyamotoi, transmitted by Ixodes spp., has recently spawned new interest in this bacterial group. In this review, recent data on tick-host-pathogen interactions for tick-borne relapsing fevers is presented, with special focus on B. miyamotoi. PMID:29670860

Pre-treatment haemoglobin and peripheral blood lymphocyte count as independent predictors of outcome in carcinoma of cervix.

PubMed

Hoskin, P J; Rojas, A M; Peiris, S N; Mullassery, V; Chong, I Y

2014-04-01

To evaluate pre-treatment haemoglobin and peripheral blood lymphocyte (PBL) counts as predictors of treatment outcome in cervix carcinoma treated with radical chemoradiation. Pre-treatment PBL counts and haemoglobin concentrations were retrieved from full blood count examinations from 111 patients who received concurrent chemoradiotherapy. Overall survival and relapse-free survival were obtained using the Kaplan-Meier method by ranking the data by median haemoglobin and PBL, singly and then in association. Their independence and significance as predictors of outcome were analysed using the Cox proportional hazard model. Survival rates were significantly higher in patients whose haemoglobin level or PBL counts were at or above the corresponding median value. At 5 years, rates of overall survival were 77% versus 41% (P = 0.0003) and 75% versus 42% (P = 0.002), when dichotomised around median haemoglobin and PBL, respectively. In multivariate and univariate analyses, both PBL and haemoglobin were independent and significant predictors for risk of death and relapse. Their predictive power was dramatically enhanced when the data were stratified into four groups by associating patients with haemoglobin ≥ median or < median with those whose PBL was ≥ or < median. Baseline PBL and haemoglobin seem to be strong, independent predictors of treatment outcome in carcinoma of the cervix, particularly if patient response is ranked using the predictors simultaneously. The hypothesis needs to be tested and, if confirmed, the markers should be used in combination to identify those at greater risk of failure who may benefit from additional therapy, with further validation in prospective trials offering treatment modification. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A look at treatment strategies for relapsed multiple myeloma.

PubMed

Cetani, Giusy; Boccadoro, Mario; Oliva, Stefania

2018-05-16

Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved management of toxicities. The choice of regimen at relapse is usually based on prior response, toxicities, age and comorbidities of relapsed patients. Areas covered: A review was performed of the most recent and effective therapeutic strategies for the relapsed myeloma setting, by documenting the latest clinical evidence from phase II and III clinical trials. Of note, new drugs, such as carfilzomib, ixazomib, pomalidomide, daratumumab and elotuzumab, alone or in combinations in doublet or triplet regimens, have greatly increased the treatment armamentarium against myeloma. Expert Commentary: Impressive results have been obtained with new drugs in relapsed patients. Besides number of prior therapies and previous response, other factors play a crucial role in the selection of therapy. Re-challenge with previous drugs can be adopted if previous responses lasted at least 6 months and therapy had induced low toxicity. Patients' risk status can further help to appropriately select therapy at relapse, and clinical trials will allow physicians to use newer targeted therapies and immune-therapies, thus delaying palliative approaches to later relapse stages.

Relapse Prevention in Health Promotion: Strategies and Long-Term Outcome.

ERIC Educational Resources Information Center

Gintner, Gary G.

1988-01-01

Reviews the efficacy of maintenance enhancement procedures to prevent relapse in smoking cessation, weight control, and exercise programs. Presents models of maintenance enhancement, reviews studies that have used relapse prevention strategies, and discusses ways of incorporating relapse prevention techniques into health promotion programs.…

Are prostatic calculi independent predictive factors of lower urinary tract symptoms?

PubMed Central

Park, Sung-Woo; Nam, Jong-Kil; Lee, Sang-Don; Chung, Moon-Kee

2010-01-01

We determined the correlation between prostatic calculi and lower urinary tract symptoms (LUTS), as well as the predisposing factors of prostatic calculi. Of the 1 527 patients who presented at our clinic for LUTS, 802 underwent complete evaluations, including transrectal ultrasonography, voided bladder-3 specimen and international prostatic symptoms score (IPSS). A total of 335 patients with prostatic calculi and 467 patients without prostatic calculi were divided into calculi and no calculi groups, respectively. Predictive factors of severe LUTS and prostatic calculi were determined using uni/multivariate analysis. The overall IPSS score was 15.7 ± 9.2 and 14.1 ± 9.2 in the calculi and no calculi group, respectively (P = 0.013). The maximum flow rate was 12.1 ± 6.9 and 14.2 ± 8.2 mL s−1 in the calculi and no calculi group, respectively (P = 0.003). On univariate analysis for predicting factors of severe LUTS, differences on age (P = 0.042), prostatic calculi (P = 0.048) and prostatitis (P = 0.018) were statistically significant. However, on multivariate analysis, no factor was significant. On multivariate analysis for predisposing factors of prostatic calculi, differences on age (P < 0.001) and prostate volume (P = 0.001) were significant. To our knowledge, patients who have prostatic calculi complain of more severe LUTS. However, prostatic calculi are not an independent predictive factor of severe LUTS. Therefore, men with prostatic calculi have more severe LUTS not only because of prostatic calculi but also because of age and other factors. In addition, old age and large prostate volume are independent predisposing factors for prostatic calculi. PMID:19966831

Are prostatic calculi independent predictive factors of lower urinary tract symptoms?

PubMed

Park, Sung-Woo; Nam, Jong-Kil; Lee, Sang-Don; Chung, Moon-Kee

2010-03-01

We determined the correlation between prostatic calculi and lower urinary tract symptoms (LUTS), as well as the predisposing factors of prostatic calculi. Of the 1 527 patients who presented at our clinic for LUTS, 802 underwent complete evaluations, including transrectal ultrasonography, voided bladder-3 specimen and international prostatic symptoms score (IPSS). A total of 335 patients with prostatic calculi and 467 patients without prostatic calculi were divided into calculi and no calculi groups, respectively. Predictive factors of severe LUTS and prostatic calculi were determined using uni/multivariate analysis. The overall IPSS score was 15.7 +/- 9.2 and 14.1 +/- 9.2 in the calculi and no calculi group, respectively (P = 0.013). The maximum flow rate was 12.1 +/- 6.9 and 14.2 +/- 8.2 mL s(-1) in the calculi and no calculi group, respectively (P = 0.003). On univariate analysis for predicting factors of severe LUTS, differences on age (P = 0.042), prostatic calculi (P = 0.048) and prostatitis (P = 0.018) were statistically significant. However, on multivariate analysis, no factor was significant. On multivariate analysis for predisposing factors of prostatic calculi, differences on age (P < 0.001) and prostate volume (P = 0.001) were significant. To our knowledge, patients who have prostatic calculi complain of more severe LUTS. However, prostatic calculi are not an independent predictive factor of severe LUTS. Therefore, men with prostatic calculi have more severe LUTS not only because of prostatic calculi but also because of age and other factors. In addition, old age and large prostate volume are independent predisposing factors for prostatic calculi.

Postpartum smoking relapse--a thematic synthesis of qualitative studies.

PubMed

Notley, Caitlin; Blyth, Annie; Craig, Jean; Edwards, Alice; Holland, Richard

2015-11-01

Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on women's experience of postpartum smoking relapse. A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Women's beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse. © 2015 Society for the Study of Addiction.

Statistical definition of relapse: case of family drug court.

PubMed

Alemi, Farrokh; Haack, Mary; Nemes, Susanna

2004-06-01

At any point in time, a patient's return to drug use can be seen either as a temporary event or as a return to persistent use. There is no formal standard for distinguishing persistent drug use from an occasional relapse. This lack of standardization persists although the consequences of either interpretation can be life altering. In a drug court or regulatory situation, for example, misinterpreting relapse as return to drug use could lead to incarceration, loss of child custody, or loss of employment. A clinician who mistakes a client's relapse for persistent drug use may fail to adjust treatment intensity to client's needs. An empirical and standardized method for distinguishing relapse from persistent drug use is needed. This paper provides a tool for clinicians and judges to distinguish relapse from persistent use based on statistical analyses of patterns of client's drug use. To accomplish this, a control chart is created for time-in-between relapses. This paper shows how a statistical limit can be calculated by examining either the client's history or other clients in the same program. If client's time-in-between relapse exceeds the statistical limit, then the client has returned to persistent use. Otherwise, the drug use is temporary. To illustrate the method, it is applied to data from three family drug courts. The approach allows the estimation of control limits based on the client's as well as the court's historical patterns. The approach also allows comparison of courts based on recovery rates.

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

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

PubMed

Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Lee, Soon Il; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

2016-11-01

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study

PubMed Central

Kim, Seok Jin; Hong, Jun Sik; Chang, Myung Hee; Kim, Jeong-A; Kwak, Jae-Yong; Kim, Jin Seok; Yoon, Dok Hyun; Lee, Won Sik; Do, Young Rok; Kang, Hye Jin; Eom, Hyeon-Seok; Park, Yong; Won, Jong-Ho; Mun, Yeung-Chul; Kim, Hyo Jung; Kwon, Jung Hye; Kong, Jee Hyun; Oh, Sung Yong; Lee, Sunah; Bae, Sung Hwa; Yang, Deok-Hwan; Jun, Hyun Jung; Kim, Yang Soo; Yun, Hwan Jung; Il Lee, Soon; Kim, Min Kyoung; Park, Eun Kyung; Kim, Won Seog; Suh, Cheolwon

2016-01-01

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4–29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448. PMID:27713132

Incidence and risk factors for relapses in HIV-associated non-Hodgkin lymphoma as observed in the German HIV-related lymphoma cohort study.

PubMed

Schommers, Philipp; Gillor, Daniel; Hentrich, Marcus; Wyen, Christoph; Wolf, Timo; Oette, Mark; Zoufaly, Alexander; Wasmuth, Jan-Christian; Bogner, Johannes R; Müller, Markus; Esser, Stefan; Schleicher, Alisa; Jensen, Björn; Stoehr, Albrecht; Behrens, Georg; Schultze, Alexander; Siehl, Jan; Thoden, Jan; Taylor, Ninon; Hoffmann, Christian

2018-05-01

Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate. Copyright © 2018 Ferrata Storti Foundation.

Relapse among cigarette smokers: the CARDIA longitudinal study - 1985-2011.

PubMed

Caraballo, Ralph S; Kruger, Judy; Asman, Kat; Pederson, Linda; Widome, Rachel; Kiefe, Catarina I; Hitsman, Brian; Jacobs, David R

2014-01-01

There is little information about long-term relapse patterns for cigarette smokers. To describe long-term prevalence of relapse and related smoking patterns by sex, race, age, and education level among a community-based cohort of young adults followed for 25 years. We examined 25 years of data from Coronary Artery Risk Development in Young Adults (CARDIA), an ongoing study of a community-based cohort of 5115 men and women aged 18 to 30 years at baseline with periodic re-examinations. At each examination smoking, quitting, and relapse were queried. We examined prevalence of smoking relapse among 3603 participants who attended at least 6 of the 8 examinations. About 53% of 3603 participants never reported smoking on a regular basis. Among the remaining 1682 ever smokers, 52.8% of those who reported current smoking at baseline were still smoking by the end of the study, compared to 10.7% of those who initiated smoking by year 5. Among those classified as former smokers at baseline, 39% relapsed at least once; of these, 69.5% had quit again by the end of the study. Maximum education level attained, age at study baseline, and race were associated with failure to quit smoking by the end of the study and relapse among those who did quit. Maximum education level attained and age at study baseline were also associated with ability to successfully quit after a relapse. Smoking relapse after quitting is common, especially in those with lower education level. Education was the strongest predictor of all three outcomes. Improvements in access to treatment and treatment options, especially for underserved populations, are needed to prevent relapse when smokers quit. Published by Elsevier Ltd.

Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

PubMed

Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

2012-12-01

Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

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

The Relationship between Relapse Prevention Treatment Outcome and Self-Efficacy.

ERIC Educational Resources Information Center

Cantrell, Peggy J.; And Others

The majority of alcoholics and drug addicts relapse after treatment, with many substance abusers developing a chronic relapse pattern. For this study, 43 patients, who went through a 3-week inpatient relapse prevention program, answered the Situational Confidence Questionnaire (a measure of self-efficacy for alcohol-related, high-risk situations)…

Rituximab for relapsing-remitting multiple sclerosis.

PubMed

He, Dian; Guo, Rui; Zhang, Fubo; Zhang, Chao; Dong, Shuai; Zhou, Hongyu

2013-12-06

of follow-up equal to or greater than one year evaluating rituximab, as monotherapy or combination therapy, versus placebo or approved DMDs for patients with RRMS without restrictions regarding dosage, administration frequency and duration of treatment. We used the standard methodological procedures of The Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. Principal investigators of included studies were contacted for additional data or confirmation of data. One trial involving 104 adult RRMS patients with an entry score ≤ 5.0 on the Expanded Disability Status Scale (EDSS) and at least one relapse during the preceding year was included. This trial evaluated rituximab as monotherapy versus placebo, with a single course of 1000 mg intravenous rituximab (on day 1 and day 15). A significant attrition bias was found at week 48 (24.0%). Patients receiving rituximab had a significant reduction in total number of gadolinium-enhancing lesions at week 24 (mean number 0.5 versus 5.5; relative reduction 91%) and in annualised rate of relapse at week 24 (0.37 versus 0.84) but not at week 48 (0.37 versus 0.72). Disability progression was not included as an outcome in this trial. More patients in the rituximab group had adverse events within the 24 hours after the first infusion (78.3% versus 40.0%), such as chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation, pharyngolaryngeal pain, and most were mild-to-moderate events (92.6%). The most common infection-associated adverse events (> 10% in the rituximab group) were nasopharyngitis, upper respiratory tract infections, urinary tract infections and sinusitis. Among them, only urinary tract infections (14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. One ongoing trial was identified. There is not sufficient evidence to support the use of

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

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.

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

Power2: Relapse Management with Adolescents Who Stutter.

ERIC Educational Resources Information Center

Blood, Gordon W.

1995-01-01

This article describes a cognitive-behavioral treatment package for relapse management in adolescents who stutter. The package includes game-based training techniques in problem solving, communication skills, and assertiveness; coping responses for stuttering episodes; and realistic expectations for fluency and relapse. Follow-up results with…

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.

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

Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder

PubMed Central

Kessler, Remi A.; Mealy, Maureen A.

2016-01-01

Objective: The purpose of this study was to review cases of neuromyelitis optica spectrum disorder (NMOSD) relapses and pseudorelapses to identify early features that differentiate between them at onset of symptoms. Methods: This was a retrospective analysis of 74 hospitalizations of patients with NMOSD who were admitted to the Johns Hopkins Hospital for workup and treatment of a presumed relapse. Standard workup included MRI and blood and urine testing for metabolic and infectious etiologies. The gold standard for a relapse was defined as new or worsening symptoms and a change in neurologic examination correlating with a new or enhancing MRI lesion. A pseudorelapse was a clinical exacerbation with similar symptoms and signs but the MRI was negative, and workup identified an alternative cause for the symptoms that, when treated, resulted in the improvement of neurologic symptoms. Factors considered to be early predictors of relapses vs pseudorelapses were analyzed using the Fisher test. Results: Among 74 NMOSD hospitalizations for presumed relapse, 57 were confirmed relapses while 17 had a negative MRI and an identifiable cause of pseudorelapse. The most common causes of pseudorelapse were infection, pain, and dysautonomia. The only early predictor that reliably differentiated relapse from pseudorelapse among this NMOSD patient population was vision loss (p = 0.039). Race, sex, presentations of weakness, numbness, and bowel/bladder dysfunction, white blood cell count, and urinary tract infection were not different among patients with relapses vs pseudorelapses. Conclusions: Vision loss in NMOSD is strongly suggestive of a true relapse vs a pseudorelapse. Pseudorelapses localized to the spinal cord in patients with previous myelitis presented similarly to true relapses and could only be ruled out by a negative MRI. PMID:27508210

Spiritual Well-Being and Associated Factors with Relapse in Opioid Addicts.

PubMed

Noormohammadi, Mohammad-Reza; Nikfarjam, Masoud; Deris, Fatemeh; Parvin, Neda

2017-03-01

Opioid dependence relapse is a complex and multidimensional problem, and lack of spiritual well-being is a major concern in opioid addicts. This study was conducted to determine spiritual well-being and factors associated with relapse among opioid addicts. This cross-sectional study was conducted from April 2015 to September 2015. According to purposive sampling, 312 eligible addicted patients were enrolled in the study. The patients had at least an attempt of detoxification in the past six months and referred to an outpatient detoxification clinic in Shahrekord (Southwest, Iran). They completed Paloutzian and Ellison's Spiritual Well-being Scale. A researcher-developed questionnaire consisting of demographic characteristics and 20 questions about associated factors with relapse was administered. Data were analysed by version 16.0 (SPSS Inc.,Chicago, IL) using one-way ANOVA, Pearson's correlation test, chi-square, Friedman test, and student's t-test. The most important factors associated with opioid dependence relapse consist of relation with an addict friend, unemployment, living expenses, family conflicts, and somatic pain. In the present study, 157 patients had never experienced relapse while the mean of relapse in the rest participants was (3.25±1.53) times. Furthermore, the addicted patients with relapse had significantly lower scores of spiritual well-being and its subscales compared with non-relapse patients (p<0.001). The findings of the present study indicate the necessity of paying attention to spiritual well-being, family and economical, personal, and occupational factors as crucial factors in opiate addiction relapse.

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.

Pyrexia-associated Relapse in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Report.

PubMed

Ueda, Jun; Yoshimura, Hajime; Kohara, Nobuo

2018-04-27

Chronic inflammatory demyelinating polyradiculoneuropathy is a relapsing-remitting or chronic progressive demyelinating polyradiculoneuropathy. We report the case of a patient with chronic inflammatory demyelinating polyradiculoneuropathy who experienced relapses on four occasions after experiencing pyrexia and flu-like symptoms. Our patient showed characteristic features, such as relapse after pyrexia and flu-like symptoms, remission after pyretolysis without treatment, and the absence of remarkable improvement in a nerve conduction study in the remission phase. The serum level of tumor necrosis factor-α was elevated in the relapse phase and reduced in the remission phase; thus, the induction of cytokine release by viral infection might have caused the relapses.

Novel therapeutic options for relapsed hairy cell leukemia.

PubMed

Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

2015-01-01

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

A Serum Protein Profile Predictive of the Resistance to Neoadjuvant Chemotherapy in Advanced Breast Cancers*

PubMed Central

Hyung, Seok-Won; Lee, Min Young; Yu, Jong-Han; Shin, Byunghee; Jung, Hee-Jung; Park, Jong-Moon; Han, Wonshik; Lee, Kyung-Min; Moon, Hyeong-Gon; Zhang, Hui; Aebersold, Ruedi; Hwang, Daehee; Lee, Sang-Won; Yu, Myeong-Hee; Noh, Dong-Young

2011-01-01

Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies. PMID:21799047

BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

PubMed

Gambichler, T; Rooms, I; Scholl, L; Stockfleth, E; Stücker, M; Sand, M

2016-11-01

Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. © 2016 European Academy of Dermatology and Venereology.

Independence and interdependence predict health and wellbeing: divergent patterns in the United States and Japan.

PubMed

Kitayama, Shinobu; Karasawa, Mayumi; Curhan, Katherine B; Ryff, Carol D; Markus, Hazel Rose

2010-01-01

A cross-cultural survey was used to examine two hypotheses designed to link culture to wellbeing and health. The first hypothesis states that people are motivated toward prevalent cultural mandates of either independence (personal control) in the United States or interdependence (relational harmony) in Japan. As predicted, Americans with compromised personal control and Japanese with strained relationships reported high perceived constraint. The second hypothesis holds that people achieve wellbeing and health through actualizing the respective cultural mandates in their modes of being. As predicted, the strongest predictor of wellbeing and health was personal control in the United States, but the absence of relational strain in Japan. All analyses controlled for age, gender, educational attainment, and personality traits. The overall pattern of findings underscores culturally distinct pathways (independent versus interdependent) in achieving the positive life outcomes.

Association between specific plasmids and relapse in typhoid fever.

PubMed Central

Gotuzzo, E; Morris, J G; Benavente, L; Wood, P K; Levine, O; Black, R E; Levine, M M

1987-01-01

We studied isolates from 73 patients hospitalized with typhoid fever in Lima, Peru. Of these 73 patients, 11 (15%) suffered a clinical relapse, with fever and positive blood cultures, within 3 months of their original illness. Using plasmids as epidemiologic markers, we found that three patients who subsequently relapsed were initially infected with more than one strain of Salmonella typhi. There was a highly significant association between relapse and isolation of a strain containing either a 24- or a 38-kilobase plasmid at the time of the original infection; however, we were unable to show any evidence of homology between these two plasmids. Our data indicate that infection with multiple strains is not uncommon in this endemic area and suggest that relapse may be partly strain dependent. Images PMID:2821064

Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.

PubMed

Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Wierda, William G; O'Brien, Susan M; Estrov, Zeev; Ledesma, Celina; Rezvani, Katayoun; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Popat, Uday; Anderlini, Paolo; Yago, Nieto; Ciurea, Stefan O; Kebriaei, Partow; Champlin, Richard; Shpall, Elizabeth J; Hosing, Chitra M

2017-05-01

There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty-three patients were treated with immunomodulation for relapse post-alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T-cell chimerism post-alloSCT for CLL. © 2017 John Wiley & Sons Ltd.

Looking forward and back to relapse: implications for research and practice.

PubMed

Connors, G J; Longabaugh, R; Miller, W R

1996-12-01

In this commentary, the three principal investigators of the Relapse Replication and Extension Project (RREP) reflect on clinical and research implications of study findings from the three collaborating sites. A primary purpose of RREP was to study the reliability and validity of a taxonomy of relapse antecedents originally proposed by Marlatt two decades ago. Under the best of research conditions, with extensive training and practice, it was difficult to achieve reliability of coding with the original three-level system, although with only two levels of classification more reasonable albeit variable reliability was found. Modifications may improve the taxonomy's reliability, but RREP data indicate that a more appropriate strategy is to measure possible antecedents of relapse by continuous scales such as those provided by Annis, Heather and Litman. There is reasonably consistent evidence for two common antecedents of relapse: negative emotional states, and positive emotional states in a social context. Antecedents of relapse show only modest consistency within individuals from one occasion to the next. The causes to which clients attribute relapses may exert a significant effect on future drinking episodes. Stable and internal attributions, such as are commonly associated with a dispositional disease model, may serve to perpetuate relapse. From the RREP studies, the availability of coping skills appears to be a potent protective factor, and ineffective coping a consistent predictor of relapse. Implications for clinical research and practice are considered.

Brain structural, neurochemical and neuroinflammatory markers of psychosis onset and relapse: Is there evidence for a psychosis relapse signature?

PubMed

Cropley, Vanessa; Wood, Stephen J; Pantelis, Christos

2013-05-10

Schizophrenia is a debilitating illness that is often associated with progressive clinical deterioration following repeated episodes of illness. Despite the clinical evidence for clinical attrition, the nature of any associated neurobiological pathology has not been examined systematically. This review examines the neurobiological imaging markers associated with psychosis onset and relapse and considers whether these may be potential state markers of acute psychosis. We report several markers of neurobiological changes associated with acute psychosis. These include dynamic changes in brain structure in the frontal and temporal regions, neurochemical alterations in dopamine and glutamate and evidence for neuroinflammation through microglial activation. We propose that with the use of repeat longitudinal assessments of brain imaging markers over the course of a psychosis relapse, the neurobiological trajectory indicative of a 'relapse signature' for psychosis will be identified.

Animal Models of Fear Relapse

PubMed Central

Goode, Travis D.; Maren, Stephen

2014-01-01

Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. PMID:25225304

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80

PubMed Central

Leng, Xiaoyan; La Monte, Michael J.; Tindle, Hilary A.; Cochrane, Barbara B.; Shumaker, Sally A.

2016-01-01

Abstract Background. We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65–80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. Methods. Women’s Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [ SD ] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). Results. Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. Conclusions. Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65–80) has far-reaching implications for improving late-life (after age 80) functional independence. PMID:26858328

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.

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.

Independence and Interdependence Predict Health and Wellbeing: Divergent Patterns in the United States and Japan

PubMed Central

Kitayama, Shinobu; Karasawa, Mayumi; Curhan, Katherine B.; Ryff, Carol D.; Markus, Hazel Rose

2010-01-01

A cross-cultural survey was used to examine two hypotheses designed to link culture to wellbeing and health. The first hypothesis states that people are motivated toward prevalent cultural mandates of either independence (personal control) in the United States or interdependence (relational harmony) in Japan. As predicted, Americans with compromised personal control and Japanese with strained relationships reported high perceived constraint. The second hypothesis holds that people achieve wellbeing and health through actualizing the respective cultural mandates in their modes of being. As predicted, the strongest predictor of wellbeing and health was personal control in the United States, but the absence of relational strain in Japan. All analyses controlled for age, gender, educational attainment, and personality traits. The overall pattern of findings underscores culturally distinct pathways (independent versus interdependent) in achieving the positive life outcomes. PMID:21833228

Relapse following successful electroconvulsive therapy for major depression: a meta-analysis.

PubMed

Jelovac, Ana; Kolshus, Erik; McLoughlin, Declan M

2013-11-01

High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7-57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7-45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4-53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio=0.49, 95% CI=0.39-0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved.

A conflict rat model of cue-induced relapse to cocaine seeking.

PubMed

Cooper, Ayelet; Barnea-Ygael, Noam; Levy, Dino; Shaham, Yavin; Zangen, Abraham

2007-09-01

Relapse to drug use in humans can be induced by exposure to drug-associated cues. The ability of drug cues to provoke 'relapse' has been studied in laboratory animals using a reinstatement model in which resumption of drug seeking is assessed after extinction of drug-reinforced responding. In this model, there are no adverse consequences of drug-seeking behavior. However, in humans, abstinence is often self-imposed, and relapse episodes likely involve making a choice between the desire for the drug and the negative consequences of pursuing it (a conflict situation). In this paper, we describe a conflict model of cue-induced relapse in rats that approximate the human condition. Rats were trained to lever press for cocaine; infusions were paired with a discrete light cue. An 'electric barrier' was then introduced by electrifying the floor area near the levers. Responding decreased over days with increasing shock intensities, until the rats did not approach the levers for 3 days. Subsequently, the effect of intermittent noncontingent light-cue presentations on resumption of lever responding (relapse) was assessed in extinction tests, with the electric barrier remaining activated; during testing, lever presses led to contingent light-cue presentations. Noncontingent cue exposure led to resumption of lever presses during the relapse tests in 14 of the 24 rats. Surprisingly, 24 h later, 11 of the 24 rats resumed lever responding in a subsequent post-noncontingent cue test under similar extinction conditions. Large individual differences in responding were observed during both tests. At its current stage of development, the conflict relapse model appears particularly suitable for studying individual differences in cue-induced relapse to cocaine seeking or factors that promote this relapse.

Is Obesity Predictive of Cardiovascular Dysfunction Independent of Cardiovascular Risk Factors?

PubMed Central

DeVallance, Evan; Fournier, Sara B.; Donley, David A.; Bonner, Daniel E.; Lee, Kyuwan; Frisbee, Jefferson C.; Chantler, Paul D.

2015-01-01

Introduction Obesity is thought to exert detrimental effects on the cardiovascular (CV) system. However, this relationship is impacted by the co-occurrence of CV risk factors, type II diabetes (T2DM), and overt disease. We examined the relationships between obesity, assessed by body mass index (BMI) and waist circumference (WC), and CV function in 102 subjects without overt CV disease. We hypothesized that obesity would be independently predictive of CV remodeling and functional differences, especially at peak exercise. Methods Brachial (bSBP) and central (cSBP) systolic pressure, carotid-to-femoral pulse wave velocity (PWVcf) augmentation index (AGI) (by SphygmoCor), and carotid remodeling (B-mode ultrasound) were examined at rest. Further, peak exercise cardiac imaging (Doppler ultrasound) was performed to measure the coupling between the heart and arterial system. Results In backward elimination regression models, accounting for CV risk factors, neither BMI nor WC were predictors of carotid thickness or PWVcf; rather age, triglycerides, and hypertension were the main determinants. However, BMI and WC predicted carotid cross-sectional area and lumen diameter. When examining the relationship between body size and SBP, BMI (β=0.32) and WC (β=0.25) were predictors of bSBP (p<0.05), whereas, BMI was the only predictor of cSBP (β=0.22, p<0.05) indicating a differential relationship between cSBP, bSBP and body size. Further, BMI (β=−0.26) and WC (β=−0.27) were independent predictors of AGI (p<0.05). As for resting cardiac diastolic function, WC seemed to be a better predictor than BMI. However, both BMI and WC were inversely and independently related to arterial elastance (net arterial load) and end-systolic elastance (cardiac contractility) at rest and peak exercise. Discussion These findings illustrate that obesity, without T2DM and overt CV disease, and after accounting for CV risk factors, is susceptible to pathophysiological adaptations that may

Perinatal Substance Use: A Prospective Evaluation of Abstinence and Relapse

PubMed Central

Forray, Ariadna; Merry, Brian; Lin, Haiqun; Ruger, Jennifer Prah; Yonkers, Kimberly A.

2015-01-01

Background Substance use decreases in pregnancy but little prospective data are available on the rates of abstinence and relapse for specific substances. This study compared rates of abstinence in pregnancy and relapse postpartum for nicotine cigarettes, alcohol, marijuana, and cocaine. Methods Data from 152 women drawn from a randomized controlled trial comparing psychological treatments for substance use in pregnancy were analyzed. Self-reports of substance use and urine for toxicology testing throughout pregnancy and 3-months, 12-months and 24-months post-delivery were collected. Multivariate Cox models were used to compare rates of abstinence and relapse across substances. Results In pregnancy, 83% of all women achieved abstinence to at least one substance. The mean (SE) days to abstinence was 145.81 (9.17), 132.01 (6.17), 151.52 (6.24), and 148.91 (7.68) for cigarettes, alcohol, marijuana and cocaine, respectively. Participants were more likely to achieve abstinence from alcohol (HR 7.24 (95% CI 4.47-11.72), marijuana (HR 4.06; 95% CI 1.87-6.22), and cocaine (HR 3.41; 95% CI 2.53-6.51), than cigarettes. Postpartum, 80% of women abstinent in the last month of pregnancy relapsed to at least one substance. The mean days to relapse was 109.67 (26.34), 127.73 (21.29), 138.35 (25.46), and 287.55 (95.85) for cigarettes, alcohol, marijuana and cocaine, respectively. Relapse to cocaine was only 34% (HR 0.34; 95% CI 0.15-0.77) that of cigarettes. Conclusions Pregnancy-related abstinence rates were high for all substances except cigarettes. Postpartum relapse was common, with cocaine using women being less likely to relapse after attaining abstinence compared to women using cigarettes, alcohol or marijuana. PMID:25772437

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.

Rituximab used in three cases with relapsed non-Hodgkin’s lymphoma

PubMed Central

ELLI, MURAT; YILMAZ, SEMA; AYDIN, RAMAZAN; MURAT, SADRIYE; BILGICI, MELTEM CEYHAN; DAGDEMIR, AYHAN

2013-01-01

Relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL) patients have a poor prognosis. New treatment modalities have been used to improve survival rates in children with relapsed or refractory B-NHL. CD20 is expressed in >98% of childhood B-NHL and a chimeric anti-CD20 monoclonal antibody, rituximab, is increasingly being used at relapse. The aim of the present study was to determine the efficacy of rituximab on relapsed B-NHL. Three B-NHL cases were treated successfully with a combination of intensive chemotherapy protocol plus rituximab. PMID:24649209

Effect of local administration of simvastatin on postorthodontic relapse in a rabbit model.

PubMed

AlSwafeeri, Hani; ElKenany, Walid; Mowafy, Mohamed; Karam, Sahar

2018-06-01

Posttreatment relapse is a major challenging clinical issue. The objective of this study was to evaluate the effect of local administration of simvastatin on posttreatment relapse. Orthodontic tooth movement was induced in 10 white New Zealand rabbits. After 21 days of active tooth movement, the orthodontic appliances were removed, and the experimental teeth were allowed to relapse for 21 days. During the relapse phase, 1 mandibular quadrant received local simvastatin administration, and the other received the control vehicle solution on a weekly basis. Three-dimensional models of the experimental teeth were created to allow the measurement of experimental tooth movement and posttreatment relapse. The animals were killed at the end of the relapse phase for histomorphometric analysis of alveolar bone remodeling. The mean relapse percentages were 75.83% in the quadrant receiving the control vehicle solution and 62.01% in the quadrant receiving simvastatin. Neither the relapse magnitude nor the relapse percentage showed a significant difference between the 2 quadrants. Histomorphometric analyses showed that local simvastatin administration yielded a significant reduction in the area of active bone-resorptive lacunae and a significant increase in newly formed bone area. Although local administration of simvastatin aids in bone remodeling associated with posttreatment relapse by reducing the area of active bone resorption and upregulating bone formation, it did not significantly minimize posttreatment relapse. Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Continuation Electroconvulsive Therapy vs Pharmacotherapy for Relapse Prevention in Major Depression

PubMed Central

Kellner, Charles H.; Knapp, Rebecca G.; Petrides, Georgios; Rummans, Teresa A.; Husain, Mustafa M.; Rasmussen, Keith; Mueller, Martina; Bernstein, Hilary J.; O’Connor, Kevin; Smith, Glenn; Biggs, Melanie; Bailine, Samuel H.; Malur, Chitra; Yim, Eunsil; McClintock, Shawn; Sampson, Shirlene; Fink, Max

2013-01-01

Background Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. Objective To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. Design Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. Setting Five academic medical centers and their outpatient psychiatry clinics. Patients Two hundred one patients with Structured Clinical Interview for DSM-IV–diagnosed unipolar depression who had remitted with a course of bilateral ECT. Interventions Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. Main Outcome Measure Relapse of depression, compared between the C-ECT and C-Pharm groups. Results In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean±SD time to relapse for the C-ECT group was 9.1±7.0 weeks compared with 6.7±4.6 weeks for the C-Pharm group (P=.13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. Conclusions Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed

Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80.

PubMed

Vaughan, Leslie; Leng, Xiaoyan; La Monte, Michael J; Tindle, Hilary A; Cochrane, Barbara B; Shumaker, Sally A

2016-03-01

We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65-80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self-reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late-life (after age 80) functional independence. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Relapse Following Successful Electroconvulsive Therapy for Major Depression: A Meta-Analysis

PubMed Central

Jelovac, Ana; Kolshus, Erik; McLoughlin, Declan M

2013-01-01

High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7–57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7–45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4–53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio=0.49, 95% CI=0.39–0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved. PMID:23774532

Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses.

PubMed

Roux, Jonathan; Bard, Denis; Le Pabic, Estelle; Segala, Claire; Reis, Jacques; Ongagna, Jean-Claude; de Sèze, Jérôme; Leray, Emmanuelle

2017-07-01

Seasonal variation of relapses in multiple sclerosis (MS) suggests that season-dependent factors, such as ambient air pollution, may trigger them. However, only few studies have considered possible role of air pollutants as relapse's risk factor. We investigated the effect of particulate matter of aerodynamic diameter smaller than 10µm (PM 10 ) on MS relapses. In total, 536 relapsing MS patients from Strasbourg city (France) were included, accounting for 2052 relapses over 2000-2009 period. A case-crossover design was used with cases defined as the days of relapse and controls being selected in the same patient at plus and minus 35 days. Different lags from 0 to 30 days were considered. Conditional logistic regressions, adjusted on meteorological parameters, school and public holidays, were used and exposure was considered first as a quantitative variable and second, as a binary variable. The natural logarithm of the average PM 10 concentration lagged from 1 to 3 days before relapse onset was significantly associated with relapse risk (OR =1.40 [95% confidence interval 1.08-1.81]) in cold season. Consistent results were observed when considering PM 10 as a binary variable, even if not significant. With an appropriate study design and robust ascertainment of neurological events and exposure, the present study highlights the effect of PM 10 on the risk of relapse in MS patients, probably through oxidative stress mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Pattern of relapse in paediatric acute lymphoblastic leukaemia in a tertiary care unit.

PubMed

Siddiqui, Emad Uddin; Kazi, Sayyeda Ghazala; Habib, Muhammad Irfan; Ahmed Khan, Khalid Mehmood; Zia, Nukhba

2016-08-01

To determine the frequency, site and time to relapse from diagnosis, and to see the relationship of relapse with important prognostic factors. The prospective descriptive observational study was conducted at the National Institute of Child Health, Karachi, June 2005 to May 2007, and comprised newly-diagnosed cases of acute lymphoblastic leukaemia. Bone marrow aspiration was done on reappearance of blast cells in peripheral smear and cerebrospinal fluid. Detailed report was done each time when intra-thecal chemotherapy was given or there were signs and symptoms suggestive of central nervous system relapse. SPSS 12 was used for data analysis. Of the 60 patients enrolled, 4(6.6%) expired and 1(1.7%) was lost to follow-up. Of the 55(91.6%) who comprised the study sample, 35(58%) were males and 25(42%) females. Mean age of relapse was 6.8±3.27 years. Mean time to relapse from diagnosis was 1.3±0.54 years; 12(20%) patients suffered relapse, and of them 5(14%) were boys. Central nervous system relapse in 8(67%) patients was the most common site, with 3(25%) bone-marrow relapses. Out of 12 patient with relapses, 9(75%) had white blood cell count less than 50,000/cm. Relapse in acute lymphoblastic leukaemia was common, although treatment modalities are improving day by day.

Relapse and Craving in Alcohol-Dependent Individuals: A Comparison of Self-Reported Determinants.

PubMed

Snelleman, Michelle; Schoenmakers, Tim M; van de Mheen, Dike

2018-06-07

Negative affective states and alcohol-related stimuli increase risk of relapse in alcohol dependence. In research and in clinical practice, craving is often used as another important indicator of relapse, but this lacks a firm empirical foundation. The goal of the present study is to explore and compare determinants for relapse and craving, using Marlatt's (1996) taxonomy of high risk situations as a template. We conducted semi-structured interviews with 20 alcohol-dependent patients about their most recent relapse and craving episodes. Interview transcripts were carefully reviewed for their thematic content, and codes capturing the thematic content were formulated. In total, we formulated 42 relapse-related codes and 33 craving-related codes. Descriptions of craving episodes revealed that these episodes vary in frequency and intensity. The presence of alcohol-related stimuli (n = 11) and experiencing a negative emotional state (n = 11) were often occurring determinants of craving episodes. Both negative emotional states (n = 17) and testing personal control (n = 11) were viewed as important determinants of relapses. Craving was seldom mentioned as a determinant for relapse. Additionally, participants reported multiple determinants preceding a relapse, whereas craving episodes were preceded by only one determinant. Patient reports do not support the claim that craving by itself is an important proximal determinant for relapse. In addition, multiple determinants were present before a relapse. Therefore, future research should focus on a complexity of different determinants.

Retrospective and Prospective Reports of Precipitants to Relapse in Pathological Gambling

ERIC Educational Resources Information Center

Hodgins, David C.; el-Guebaly, Nady

2004-01-01

A prospective design was used to explore the precipitants of relapse in a naturalistic sample of pathological gamblers (N = 101) who had recently quit gambling. Relapse rates were high; only 8% were entirely free of gambling during the 12-month follow-up. Relapses were highly variable but occurred most frequently in the evening, when the person…

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.

New targeted therapies for relapsed pediatric acute lymphoblastic leukemia.

PubMed

Pierro, Joanna; Hogan, Laura E; Bhatla, Teena; Carroll, William L

2017-08-01

The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise. Areas covered: We performed a literature search on PubMed and recent meeting abstracts using the keywords below. We focused on the biology and clonal evolution of relapsed disease highlighting potential new targets of therapy. We further summarized the results of early trials of the three most prominent immunotherapy agents currently under investigation. Expert commentary: Discovery of targetable pathways that lead to drug resistance and recent breakthroughs in immunotherapy show great promise towards treating this aggressive disease. The best way to treat relapse, however, is to prevent it which makes incorporation of these new approaches into frontline therapy the best approach. Challenges remain to balance efficacy with toxicity and to prevent the emergence of resistant subclones which is why combining these newer agents with conventional chemotherapy will likely become standard of care.

Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation.

PubMed

Gress, Ronald E; Miller, Jeffrey S; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Landau, Dan A; Wu, Catherine J

2013-11-01

In the National Cancer Institute's Second Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Biology of Relapse discussed recent advances in understanding some of the host-, disease-, and transplantation-related contributions to relapse, emphasizing concepts with potential therapeutic implications. Relapse after hematopoietic stem cell transplantation (HSCT) represents tumor escape, from the cytotoxic effects of the conditioning regimen and from immunologic control mediated by reconstituted lymphocyte populations. Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM) effect-and relapse-include conditioning regimen effects on lymphocyte populations and homeostasis, immunologic niches, and the tumor microenvironment; reconstitution of lymphocyte populations and establishment of functional immune competence; and genetic heterogeneity within the malignancy defining potential for clonal escape. Recent developments in T cell and natural killer cell homeostasis and reconstitution are reviewed, with implications for prevention and treatment of relapse, as is the application of modern genome sequencing to defining the biologic basis of GVM, clonal escape, and relapse after HSCT. Published by Elsevier Inc.

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.

Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder.

PubMed

Mealy, Maureen A; Cook, Lawrence J; Pache, Florence; Velez, Diego L; Borisow, Nadja; Becker, Daniel; Arango, Jorge A Jimenez; Paul, Friedemann; Levy, Michael

2018-05-07

It is unknown if vaccines cause non-specific immune activation in patients with neuromyelitis optica spectrum disorder and no consensus on the use of vaccines exists for this population. We investigated the temporal association of vaccinations with relapses in patients with neuromyelitis optica spectrum disorder. This is a multi-center retrospective analysis of patients with neuromyelitis optica spectrum disorder for whom immunization history and clinical records from disease onset were available. Ninety patients who met 2015 diagnostic criteria received a total of 211 vaccinations and experienced 340 relapses over a median disease course of 6.6 years. The likelihood of a relapse occurring within 30, 60, and 90 days of a vaccine was compared to the likelihood of a relapse occurring within each time point of a randomly generated date. We also compared the relapse rate between patients who received any vaccination(s) after disease onset to those who did not. We identified seven patients with neuromyelitis optica spectrum disorder who relapsed within 30 days of a vaccination, six between 31 and 60 days, and four who relapsed between 61 and 90 days. The rate of vaccine-associated relapses within 30, 60, and 90 days was significantly higher than the likelihood of a relapse spontaneously occurring within each of the given time frames (p = 0.034, 0.01, 0.016, respectively) among patients who were not on preventive immunotherapy only. Among those who were on immunotherapy to prevent relapses, there was no significant association of relapse with vaccines. Additionally, among patients on immunotherapy, the annualized relapse rate of those who received routine vaccinations was significantly lower than in unvaccinated patients. The evidence suggests that there may be a risk of vaccination-associated relapses among untreated neuromyelitis optica spectrum disorder patients, however immunosuppressive therapy at time of vaccine may abort the risk; this suggests that the

Conditional Risk of Relapse in Surveillance for Clinical Stage I Testicular Cancer.

PubMed

Nayan, Madhur; Jewett, Michael A S; Hosni, Ali; Anson-Cartwright, Lynn; Bedard, Philippe L; Moore, Malcolm; Hansen, Aaron R; Chung, Peter; Warde, Padraig; Sweet, Joan; O'Malley, Martin; Atenafu, Eshetu G; Hamilton, Robert J

2017-01-01

Patients on surveillance for clinical stage I (CSI) testicular cancer are counseled regarding their baseline risk of relapse. The conditional risk of relapse (cRR), which provides prognostic information on patients who have survived for a period of time without relapse, have not been determined for CSI testicular cancer. To determine cRR in CSI testicular cancer. We reviewed 1239 patients with CSI testicular cancer managed with surveillance at a tertiary academic centre between 1980 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: cRR estimates were calculated using the Kaplan-Meier method. We stratified patients according to validated risk factors for relapse. We used linear regression to determine cRR trends over time. At orchiectomy, the risk of relapse within 5 yr was 42.4%, 17.3%, 20.3%, and 12.2% among patients with high-risk nonseminomatous germ cell tumor (NSGCT), low-risk NSGCT, seminoma with tumor size ≥3cm, and seminoma with tumor size <3cm, respectively. However, for patients without relapse within the first 2 yr of follow-up, the corresponding risk of relapse within the next 5 yr in the groups was 0.0%, 1.0% (95% confidence interval [CI] 0.3-1.7%), 5.6% (95% CI 3.1-8.2%), and 3.9% (95% CI 1.4-6.4%). Over time, cRR decreased (p≤0.021) in all models. Limitations include changes to surveillance protocols over time and few late relapses. After 2 yr, the risk of relapse on surveillance for CSI testicular cancer is very low. Consideration should be given to adapting surveillance protocols to individualized risk of relapse based on cRR as opposed to static protocols based on baseline factors. This strategy could reduce the intensity of follow-up for the majority of patients. Our study is the first to provide data on the future risk of relapse during surveillance for clinical stage I testicular cancer, given a patient has been without relapse for a specified period of time. Copyright © 2016 European Association of Urology. Published by Elsevier B

Distinctive clinical course and pattern of relapse in adolescents with medulloblastoma

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

Tabori, Uri; Sung, Lillian; Hukin, Juliette

2006-02-01

Purpose: To report the clinical course of adolescents with medulloblastoma, with specific emphasis on prognosis and pattern of relapse. Methods and Materials: We retrospectively studied the clinical course and outcomes of children aged 10-20 years with medulloblastoma, treated at centers throughout Canada between 1986 and 2003. To better assess time to relapse, a cohort of patients aged 3-20 years at diagnosis was generated. Results: A total of 72 adolescents were analyzed. Five-year overall survival and event-free survival rates were 78.3% {+-} 5.4% and 68.0% {+-} 6.2%, respectively. Late relapses occurred at a median of 3.0 years (range, 0.3-6.8 years). Inmore » univariate analysis, conventional risk stratification and the addition of chemotherapy to craniospinal radiation did not have prognostic significance. Female patients had improved overall survival (p = 0.007). Time to relapse increased with age in a linear fashion. After relapse, patients faired poorly regardless of treatment modality. Patients who did not receive chemotherapy initially had improved progression-free survival at relapse (p 0.05). Conclusions: Our study suggests that adolescents with medulloblastoma might have a unique prognosis and pattern of relapse, dissimilar to those in younger children. They might benefit from different risk stratifications and prolonged follow-up. These issues should be addressed in future prospective trials.« less

Maintenance, Generalization, and Treatment Relapse: A Behavioral Momentum Analysis

ERIC Educational Resources Information Center

Mace, F. Charles; Nevin, John A.

2017-01-01

Maintenance and generalization have been inconsistently defined in the behavior analytic literature. The term "treatment relapse" is used commonly in the medical and mental health literature to refer to the return of a condition that was previously considered successfully treated. Basic behavioral researchers have studied relapse related…

Isolated cognitive relapses in multiple sclerosis.

PubMed

Pardini, Matteo; Uccelli, Antonio; Grafman, Jordan; Yaldizli, Özgür; Mancardi, Gianluigi; Roccatagliata, Luca

2014-09-01

While cognition can be affected during sensorimotor multiple sclerosis (MS) relapses, the relevance of isolated cognitive relapses (ICRs ie, those occurring in absence of new sensorimotor symptoms) remain poorly characterised. Here, we decided to explore the relationship between ICR, subjective evaluation of cognitive performance and long-term cognitive decline in a group of subjects with relapsing-remitting MS. We analysed the cognitive performance of 99 clinically stable relapsing-remitting MS for whom data from four consequent clinical and cognitive evaluations were available, that is, a baseline evaluation (t₀), followed in the subsequent 6 months by a second evaluation performed not later than 2 weeks after a routine brain scan positive for at least one area of gadolinium enhancement (t₁) and two gadolinium enhancement-negative follow-up evaluations after 6 months (t₂) and 1 year (t₃) from t₁. Based on published literature, we defined as a meaningful change in cognition a transient reduction of Symbol Digit Modalities Test score of at least four points at t₁ compared with t₀ and t₂. ICRs were found in 17 patients and were not associated with subjective cognitive deficits or depression. Subjects who presented with an ICR at t₁ presented with a significantly reduced cognitive performance at the follow-up evaluations compared with patients without ICR. We showed that ICRs were not associated with changes in mood, fatigue levels or cognitive performance self-evaluations. Our study introduces an operational definition of ICRs and suggests to their role as a factor for cognitive decline in MS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Porter, David L.; Alyea, Edwin P.; Antin, Joseph H.; DeLima, Marcos; Estey, Eli; Falkenburg, J.H. Frederik; Hardy, Nancy; Kroeger, Nicolaus; Leis, Jose; Levine, John; Maloney, David G.; Peggs, Karl; Rowe, Jacob M.; Wayne, Alan S.; Giralt, Sergio; Bishop, Michael R.; van Besien, Koen

2010-01-01

Relapse is a major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT). Treatment options for relapse have been inadequate and the majority of patients ultimately die of their disease. There is no standard approach to treating relapse after alloHSCT. Withdrawal of immune suppression and donor lymphocyte infusions (DLI) are commonly used for all diseases; although these interventions are remarkably effective for relapsed CML, they have limited efficacy in other hematologic malignancies. Conventional and novel chemotherapy, monoclonal antibody therapy, targeted therapies, and second transplants have been utilized in a variety of relapsed diseases, but reports on these therapies are generally anecdotal and retrospective. As such there is an immediate need for well designed, disease-specific trials for treatment of relapse after alloHSCT. This report summarizes current treatment options under investigation for relapse after alloHSCT in a disease-specific manner. In addition, recommendations are provided for specific areas of research necessary in the treatment of relapse after alloHSCT. PMID:20699125

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.

Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making.

PubMed

Broos, Nienke; Loonstra, Rhianne; van Mourik, Yvar; Schetters, Dustin; Schoffelmeer, Anton N M; Pattij, Tommy; De Vries, Taco J

2015-07-01

Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days 1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occurred independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects. © 2014 Society for the Study of Addiction.

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.

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

Structural Ecosystems Therapy for HIV+ African-American women and drug abuse relapse.

PubMed

Feaster, Daniel J; Burns, Myron J; Brincks, Ahnalee M; Prado, Guillermo; Mitrani, Victoria B; Mauer, Megaly H; Szapocznik, Jose

2010-06-01

This report examines the effect of Structural Ecosystems Therapy (SET) for (n=143) HIV+ African-American women on rate of relapse to substance use relative to both a person-centered approach (PCA) to therapy and a community control (CC) group. A prior report has shown SET to decrease psychological distress and family hassles relative to these 2 comparison groups. In new analyses, SET and CC had a significant protective effect against relapse as compared with PCA. There is evidence that SET's protective effect on relapse was related to reductions in family hassles, whereas there was not a direct impact of change in psychological distress on rates of relapse. Lower retention in PCA, perhaps caused by the lack of a directive component to PCA, may have put these women at greater risk for relapse. Whereas SET did not specifically address substance abuse, SET indirectly protected at-risk women from relapse through reductions in family hassles.

Preventing postpartum smoking relapse: an opportunity for neonatal nurses.

PubMed

Forest, Sharron

2009-08-01

Smoking during pregnancy and exposure to environmental tobacco smoke have harmful and sometimes devastating effects on the health of the newborn. Although interventions for smoking cessation during pregnancy demonstrate effectiveness for increasing smoking abstinence, the majority of women relapse in the postpartum period. However, modifying contributing factors for relapse may improve the success of sustained abstinence. Many parents are eager to quit smoking and willing to participate in smoking cessation interventions. Through a population-based approach to healthcare, neonatal nurses are in an ideal position to prevent relapse and to promote smoking abstinence; they can coordinate and lead efforts for establishing smoking cessation strategies that integrate obstetric, newborn, and pediatric services.

Empathy and nonattachment independently predict peer nominations of prosocial behavior of adolescents

PubMed Central

Sahdra, Baljinder K.; Ciarrochi, Joseph; Parker, Philip D.; Marshall, Sarah; Heaven, Patrick

2015-01-01

There is a plethora of research showing that empathy promotes prosocial behavior among young people. We examined a relatively new construct in the mindfulness literature, nonattachment, defined as a flexible way of relating to one's experiences without clinging to or suppressing them. We tested whether nonattachment could predict prosociality above and beyond empathy. Nonattachment implies high cognitive flexibility and sufficient mental resources to step out of excessive self-cherishing to be there for others in need. Multilevel Poisson models using a sample of 15-year olds (N = 1831) showed that empathy and nonattachment independently predicted prosocial behaviors of helpfulness and kindness, as judged by same-sex and opposite-sex peers, except for when boys nominated girls. The effects of nonattachment remained substantial in more conservative models including self-esteem and peer nominations of liking. PMID:25852590

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

PubMed

Dayton, Vanessa J; McKenna, Robert W; Yohe, Sophia L; Dolan, Michelle M; Courville, Elizabeth; Alvarez, Harold; Linden, Michael A

2017-01-01

Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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.

Long-Term Outcomes and Patterns of Relapse of Early-Stage Extranodal Marginal Zone Lymphoma Treated With Radiation Therapy With Curative Intent

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

Teckie, Sewit; Qi, Shunan; Lovie, Shona

Purpose: To report the long-term outcome and patterns of relapse of a large cohort of marginal zone lymphoma (MZL) patients treated with curative-intent radiation therapy (RT) alone. Patients and Methods: We reviewed the charts of 490 consecutive patients with stage IE or IIE MZL referred between 1992 and 2012 to our institution. Of those, 244 patients (50%) were treated with RT alone. Pathology was confirmed by hematopathologists at our institution. Patient and disease factors were analyzed for association with relapse-free survival (RFS) and overall survival (OS). Results: Median age of the cohort was 59 years, and median follow-up was 5.2 years. Annmore » Arbor stage was IE in 92%. Most common disease sites were stomach (50%), orbit (18%), non-thyroid head-and-neck (8%), skin (8%), and breast (5%). Median RT dose was 30 Gy. Five-year OS and RFS were 92% and 74%, respectively. Cumulative incidence of disease-specific death was just 1.1% by 5 years. Sixty patients (24%) developed relapse of disease; 10 were in the RT field. Crude rate of transformation to pathologically confirmed large-cell lymphoma was 1.6%. On multivariable analysis, primary disease site (P=.007) was independently associated with RFS, along with age (P=.04), presence of B-symptoms (P=.02), and International Prognostic Index risk group (P=.03). All disease sites except for head-and-neck had worse RFS relative to stomach. Conclusion: Overall and cause-specific survival are high in early-stage extra-nodal MZL treated with curative RT alone. In this large cohort of 244 patients, most patients did not experience relapse of MZL after curative RT; when relapses did occur, the majority were in distant sites. Stomach cases were less likely to relapse than other anatomic sites. Transformation to large-cell lymphoma was rare.« less

Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

2004-01-01

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

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.

Relapse prevention after index electroconvulsive therapy in treatment-resistant depression

PubMed Central

Youssef, Nagy A.; McCall, W. Vaughn

2015-01-01

Background One-third of patients who suffer from depression are resistant to conventional treatments. An acute course of electroconvulsive therapy (ECT) can lead to remission of depressive symptoms in a substantial portion of the treatment-resistant patients. However, prevention of relapse with depressive symptoms after the index course of ECT can be challenging. We review pertinent studies on the topic and analyze the best strategies to avoid relapse and recurrence of depressive symptoms. Methods We performed a systematic literature review of PubMed through April 2014 for clinical trials published in English to determine if continuation ECT, continuation medication, continuation psychotherapy, or combinations of these are the best strategy to avoid relapse and recurrence of depressive symptoms after an acute course of ECT. Clinical trials comparing ≥2 of the above strategies were included in the review. Results Although there are few rigorous randomized clinical trials in this area, most studies suggest that combined continuation ECT (C-ECT) and continuation pharmacotherapy are the most effective strategy in relapse prevention. Conclusions C-ECT and continuation pharmacotherapy may be more effective than either alone for preventing relapse. However, more definitive randomized clinical trials are needed. PMID:25401716

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.

Mesalamine treatment mimicking relapse in a child with ulcerative colitis.

PubMed

Hojsak, Iva; Pavić, Ana M; Kolaček, Sanja

2014-11-01

There are reports on mesalamine-induced bloody diarrhea mimicking ulcerative colitis (UC) relapse, mostly in adults. Herein we present a case of a child with UC who developed relapse of hemorrhagic colitis related to mesalamine. A 10-year-old girl developed severe symptoms mimicking UC relapse 3 weeks after introduction of mesalamine therapy. After mesalamine was withdrawn, her symptoms improved, but deteriorated again during the challenge of mesalamine despite concomitant use of corticosteroids. This is the first case report on such a young child during the concomitant use of corticosteroids.

Joint hyperlaxity prevents relapses in clubfeet treated by Ponseti method-preliminary results.

PubMed

Cosma, Dan Ionuţ; Corbu, Andrei; Nistor, Dan Viorel; Todor, Adrian; Valeanu, Madalina; Morcuende, Jose; Man, Sorin

2018-05-07

The aim of the study was to evaluate the role of joint hyperlaxity (by Beighton score) as a protective factor for clubfoot relapse. Patients with idiopathic clubfoot treated with the Ponseti method between January 2004 and December 2012, without other congenital foot deformity, and not previously treated by open surgery were included in either the Relapse group (n = 23) if it was a clubfoot relapse or the Control group (n = 19) if no relapse was noted. Joint laxity was evaluated using the Beighton score at the latest follow-up against the Normal group (n = 22, children matched by sex and age without clubfoot deformity). We found a significantly higher joint laxity in the Control group (4.58, 95% confidence interval [CI]: 2.1-7.06) as compared to the Relapse (3.17, 95% CI: 1.53-4.81, p = 0.032) and Normal (3.14, 95% CI: 1.78-4.5, p = 0.03) groups. The univariate logistic regression showed a 5.28-times increase in the risk of relapse for a Beighton score lower than 4/9 points (odds ratio = 5.28; 95% CI = 1.29-21.5; p = 0.018). Joint hyperlaxity could be a protective factor for clubfoot relapse.

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.

Impact of the Distance of Maxillary Advancement on Horizontal Relapse After Orthognathic Surgery.

PubMed

Fahradyan, Artur; Wolfswinkel, Erik M; Clarke, Noreen; Park, Stephen; Tsuha, Michaela; Urata, Mark M; Hammoudeh, Jeffrey A; Yamashita, Dennis-Duke R

2018-04-01

The maxillary horizontal relapse following Le Fort I advancement has been estimated to be 10% to 50%. This retrospective review examines the direct association between the amounts of maxillary advancement and relapse. We hypothesize that the greater the advancement, the greater the relapse amount. Patients with class III skeletal malocclusion underwent maxillary advancement with either a Le Fort I or a Le Fort I with simultaneous mandibular setback (bimaxillary surgery) from 2008 to 2015. Patients were assessed for a history of cleft lip or cleft palate. Patients with known syndromes were excluded. Cephalometric analysis was performed to compare surgical and postsurgical changes. Of 136 patients, 47.1% were males and 61.8% had a history of cleft. The mean surgery age was 18.9 (13.8-23) years and 53.7% underwent a bimaxillary procedure. A representative subgroup of 35 patients had preoperative, immediate postoperative, and an average of 1-year postoperative lateral cephalograms taken. The mean maxillary advancement was 6.3 mm and the horizontal relapse was 1.8 mm, indicating a 28.6% relapse. A history of cleft and amount of maxillary advancement were directly correlated, whereas bone grafting of the maxillary osteotomy sites was inversely correlated with the amount of relapse ( P < .05). Our data suggest positive correlation between amount of maxillary advancement and horizontal relapse as well as a positive correlation between history of cleft and horizontal relapse. Bone grafting of the maxillary osteotomy sites has a protective effect on the relapse.

Relapse among Cigarette Smokers: The CARDIA longitudinal study - 1985–2011☆

PubMed Central

Caraballo, Ralph S.; Kruger, Judy; Asman, Kat; Pederson, Linda; Widome, Rachel; Kiefe, Catarina I.; Hitsman, Brian; Jacobs, David R.

2015-01-01

Rationale There is little information about long-term relapse patterns for cigarette smokers. Objective To describe long-term prevalence of relapse and related smoking patterns by sex, race, age, and education level among a community-based cohort of young adults followed for 25 years. Methods We examined 25 years of data from Coronary Artery Risk Development in Young Adults (CARDIA), an ongoing study of a community-based cohort of 5115 men and women aged 18 to 30 years at baseline with periodic re-examinations. At each examination smoking, quitting, and relapse were queried. We examined prevalence of smoking relapse among 3603 participants who attended at least 6 of the 8 examinations. Results About 53% of 3603 participants never reported smoking on a regular basis. Among the remaining 1682 ever smokers, 52.8% of those who reported current smoking at baseline were still smoking by the end of the study, compared to 10.7% of those who initiated smoking by year 5. Among those classified as former smokers at baseline, 39% relapsed at least once; of these, 69.5% had quit again by the end of the study. Maximum education level attained, age at study baseline, and race were associated with failure to quit smoking by the end of the study and relapse among those who did quit. Maximum education level attained and age at study baseline were also associated with ability to successfully quit after a relapse. Conclusions Smoking relapse after quitting is common, especially in those with lower education level. Education was the strongest predictor of all three outcomes. Improvements in access to treatment and treatment options, especially for underserved populations, are needed to prevent relapse when smokers quit. PMID:24172753

Craving and relapse measurement in alcoholism.

PubMed

Potgieter, A S; Deckers, F; Geerlings, P

1999-01-01

This paper attempts to summarize the measurement of craving with four different craving instruments and to relate this to definitions and measurement of relapse. The definitions of relapse may vary between studies and researchers, but are usually well defined. Five commonly used methods to measure relapse are: (1) quantity/frequency of drinking; (2) cumulative duration of abstinence (CDA); (3) post-withdrawal abstinent period; (4) stable recovery period; (5) the time line follow-back method. The definition of craving is much less clear and is mostly described as an emotional-motivational state or as obsessive-compulsive behaviour. Four self-rating instruments are briefly discussed and compared: the Obsessive-Compulsive Drinking Scale, OCDS, the Lübeck Craving Scale, LCRR, the Alcohol Craving Questionnaire, ACQ-Now-SF-R, and ordinal scales (e.g. visual analogue, Likert, or verbal descriptive scales). These instruments measure different aspects or dimensions of craving over different periods. The different dimensions measured suggest that there is still a need to conceptualize a standard interpretation of the word craving. There is a need also to measure an emotional-motivational dimension, a cognitive-behavioural dimension, expectancies, and effects on positive and negative reinforcement with different instruments or with one multidimensional instrument. It is suggested that different patients are expected to have different craving profiles.

Comparing Effectiveness of Mindfulness-Based Relapse Prevention with Treatment as Usual on Impulsivity and Relapse for Methadone-Treated Patients: A Randomized Clinical Trial.

PubMed

Yaghubi, Mehdi; Zargar, Fatemeh; Akbari, Hossein

2017-07-01

Impulsivity is one of the causes of relapse that can affect treatment outcomes. Studies have shown that addiction treatments can reduce impulsivity in drug-dependent individuals. Studies also have suggested that mindfulness is associated with impulsivity. However, no study has investigated the effectiveness of the mindfulness-based intervention on impulsivity in opioid-dependent individuals. This study aimed to compare the effectiveness of mindfulness-based relapse prevention (MBRP) with treatment as usual (TAU) in terms of impulsivity and relapse for methadone-treated patients. The present randomized controlled clinical trial was performed in Kashan, Iran, in 2015. The study population was opioid-dependent patients referred to Maintenance Treatment Centers. Seventy patients were selected by random sampling and were assigned in two groups (MBRP and TAU) randomly. The participants of two groups filled out Barratt impulsivity scale (BIS-11) as a pre-test and 8 weeks later as post-test and 2 months later as a follow-up. Both groups received methadone-therapy. The MBRP group received 8 sessions of group therapy, while the control group did not receive any group psychotherapy session. Finally, data from 60 patients were analyzed statistically. The MBRP group had decreased impulsivity significantly (P < 0.001). The mean impulsivity score was 74.76 ± 4.72 before intervention that was significantly decreased to 57.66 ± 3.73 and 58.86 ± 3.57 after the intervention and follow-up (P < 0.001), respectively. In addition, significant differences were observed between MBRP and TAU groups for relapse frequency (P < 0.050). This study showed that MBRP compared to TAU can decrease the mean impulsivity score in opioid-dependent and reduce relapse probability. These findings suggest that MBRP is useful for opioid-dependent individuals with high-level impulsivity, and relapse prevention.

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.

The effect of low-frequency mechanical vibration on retention in an orthodontic relapse model.

PubMed

Yadav, Sumit; Assefnia, Amir; Gupta, Himank; Vishwanath, Meenakshi; Kalajzic, Zana; Allareddy, Veerasathpurush; Nanda, Ravindra

2016-02-01

To investigate the effect of low-frequency mechanical vibration (LFMV) on the prevention of relapse after active orthodontic tooth movement, bone volume fraction (BVF), tissue density, and the integrity of periodontal ligament. Thirty male CD1, 12-week-old mice were used for the study. Mice were randomly divided into three groups: 1. control group, 2. relapse group, and 3. relapse + 30 Hz vibration group. In the control group, first molar was moved mesially for 7 days using nickel-titanium coil spring delivering 10g of force, whereas in relapse and relapse + 30 Hz groups, first molar was moved mesially for 7 days and then orthodontic force was removed and molar was allowed to relapse for 7 days. In relapse + 30 Hz group, LFMVs were applied at 30 Hz. Micro-focus computed tomography (micro-CT) was used for tooth movement measurements (relapse), BVF, and tissue density. Additionally, immunostaining for sclerostin, tartrate-resistant acid phosphatase staining, and picro-sirius red staining were performed on histological sections. LFMV at 30 Hz showed a tendency to decrease relapse but was not statistically significant. Micro-CT analysis showed a trend towards increase in BVF and tissue density with application of LFMV. Sclerostin expression was decreased with 30 Hz vibration. Additionally, the picro-sirius staining showed that LFMV at 30 Hz helped in maintaining the thickness and integrity of collagen fibres in periodontal ligament. This is an animal study and extrapolation of the current findings to the clinical situation must be done with caution, as there is no osteonal remodelling (secondary remodelling) in mice when compared to humans. There was no statistically significant difference in the amount of relapse between the relapse-only and relapse + 30 Hz groups. However, there was a trend of decrease in relapse with 30 Hz mechanical vibration. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved

Contextual match and cue-independence of retrieval-induced forgetting: Testing the prediction of the model by Norman, Newman, and Detre (2007).

PubMed

Hanczakowski, Maciej; Mazzoni, Giuliana

2013-05-01

Retrieval-induced forgetting (RIF) is the finding of impaired memory performance for information stored in long-term memory due to retrieval of a related set of information. This phenomenon is often assigned to operations of a specialized mechanism recruited to resolve interference during retrieval by deactivating competing memory representations. This inhibitory account is supported by, among others, findings showing that RIF occurs with independent cues not used during retrieval practice. However, these findings are not always consistent. Recently, Norman, Newman, and Detre (2007) have proposed a model that aims at resolving discrepancies concerning cue-independence of RIF. The model predicts that RIF should be present with independent cues when episodic associations are created between independent cues and their targets in the same episodic context that is later used to cue memory during retrieval practice. In the present study we aimed to test this prediction. We associated studied items with semantically unrelated words during the main study phase of the retrieval practice paradigm, and we tested memory with both cues used during retrieval practice (Experiment 2) and episodic associates serving as independent cues (Experiments 3a and 3b). Although RIF was present when the same cues were used during retrieval practice and a final test, contrary to the prediction formulated by Norman et al., RIF failed to emerge when episodic associates were employed as independent cues.

[Risk factors and incidence of relapse in lung tuberculosis patients].

PubMed

Moreno-Martínez, Roberto; Rodríguez-Abrego, Gabriela; Martínez-Montañez, Olga G

2007-01-01

To determine the incidence of relapse in patients with lung tuberculosis and its associated risk factors. A follow up study was conducted with 237 patients who were cured after receiving treatment in rural medical facilities from the State of Chiapas. The global incidence of relapse was 1.04 cases per 100 month/person. The risk factors for relapse were lack of knowledge about treatment (OR = 2.28; 95% CI = 1.06-4.89); drug adverse effects (OR = 2.78; 95% CI = 1.31-5.90), waiting time for more than 15 minutes to receive medical care (OR = 3.07; 95% CI = 1.06-12.94) and lack of medical supervision (OR = 4.77; 95% CI = 1.30-17.41). Most of the risk factors for relapse are susceptible to modification and are related with the quality of medical care provided to lung tuberculosis patients.

Preventing Postpartum Smoking Relapse: A Randomized Clinical Trial.

PubMed

Levine, Michele D; Cheng, Yu; Marcus, Marsha D; Kalarchian, Melissa A; Emery, Rebecca L

2016-04-01

Most women who quit smoking during pregnancy will relapse postpartum. Previous efforts to prevent postpartum relapse have been unsuccessful at increasing rates of sustained abstinence. To evaluate the relative efficacy of 2 different approaches to prevent postpartum smoking relapse. Pregnant women who recently had quit smoking were recruited before the end of pregnancy. Intervention sessions were conducted through a combination of telephone calls and in-person visits beginning at delivery and continuing through 24 weeks postpartum. Participants completed assessments at the prenatal baseline and at 12, 24, and 52 weeks postpartum. Participants were recruited between March 2008 and December 2012. The dates of the analysis were April 2014 to February 2015. Women received postpartum-adapted, behavioral smoking relapse prevention intervention and were randomly assigned to an enhanced cognitive behavioral intervention that included additional specialized strategies and content focused on women's postpartum concerns about mood, stress, and weight (Strategies to Avoid Returning to Smoking [STARTS]) or a supportive, time and attention-controlled comparison (SUPPORT). Intervention began before delivery and continued through 24 weeks postpartum. The primary outcome was biochemically confirmed sustained tobacco abstinence at 52 weeks postpartum. Secondary outcomes were self-reported mood, levels of perceived stress, and degree of concern about smoking-related weight gain. The study cohort comprised 300 participants (150 randomly assigned to each group). Their mean (SD) age was 24.99 (5.65) years. Overall, 38.0% (114 of 300), 33.7% (101 of 300), and 24.0% (72 of 300) of the sample maintained abstinence at 12, 24, and 52 weeks' postpartum, respectively. There were no differences between the intervention groups in abstinence or time to relapse. Self-reported depressive symptoms and perceived stress significantly improved over time, and improvements were similar for both

Comparison of PR3-ANCA and MPO-ANCA Epitope Specificity upon Disease Relapse

EPA Science Inventory

BACKGROUND Relapse is a major clinical problem in ANCA vasculitis that causes increased morbidity and mortality. Compared to MPO-ANCA patients, patients with PR3-ANCA run a significantly increased risk of experiencing relapses. We hypothesized that a relapsing patient is produ...

Gut microbiota composition and relapse risk in pediatric MS: A pilot study.

PubMed

Tremlett, Helen; Fadrosh, Douglas W; Faruqi, Ali A; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Lynch, Susan; Waubant, Emmanuelle

2016-04-15

We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p=0.001 log-rank test), expansion of the Firmicutes (p=0.003), and presence of the Archaea Euryarchaeota (p=0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: 1.2-9.0), p=0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course. Copyright © 2016 Elsevier B.V. All rights reserved.

Usefulness of the UCSD Performance-based Skills Assessment (UPSA) for Predicting Residential Independence in Patients with Chronic Schizophrenia

PubMed Central

Mausbach, Brent T.; Bowie, Christopher R.; Harvey, Philip D.; Twamley, Elizabeth W.; Goldman, Sherrill R.; Jeste, Dilip V.; Patterson, Thomas L.

2009-01-01

The objective of this study was to examine the sensitivity and specificity of a performance-based measure of functional capacity, the UCSD Performance-Based Skills Assessment (UPSA) for the prediction of independent living status in patients with chronic schizophrenia-related conditions. A sample of 434 adults with schizophrenia or schizoaffective disorder was administered the UPSA and assessed for independent living status. Participants were classified as “independent” if they were living alone in an apartment, house, or single-resident occupancy (e.g., hotel room) and non-independent if they resided in a care facility (e.g., Board-and-Care home, Skilled Nursing Facility). Receiver Operator Characteristic (ROC) curves were calculated with the UPSA and Mattis’ Dementia Rating Scale (DRS) scores as predictor variables and residential independence as the state variable. Of the 434 participants, 99 (23%) were living independently at the time of assessment. The discriminant validity of the UPSA was adequate (ROC area under the curve = 0.74; 95% CI: 0.68–0.79), with greatest dichotomization for the UPSA at a cutoff score of 75 (68% accuracy, 69% sensitivity, 66% specificity), or 80 (68% accuracy, 59% sensitivity, 76% specificity). The UPSA was also a significantly better predictor of living status than was the DRS, based on ROC (z = 2.43, p = .015). The UPSA is a brief measure of functional capacity that predicts the ability of patients with schizophrenia to reside independently in the community. PMID:17303168

Prospective clinical validation of independent DVH prediction for plan QA in automatic treatment planning for prostate cancer patients.

PubMed

Wang, Yibing; Heijmen, Ben J M; Petit, Steven F

2017-12-01

To prospectively investigate the use of an independent DVH prediction tool to detect outliers in the quality of fully automatically generated treatment plans for prostate cancer patients. A plan QA tool was developed to predict rectum, anus and bladder DVHs, based on overlap volume histograms and principal component analysis (PCA). The tool was trained with 22 automatically generated, clinical plans, and independently validated with 21 plans. Its use was prospectively investigated for 50 new plans by replanning in case of detected outliers. For rectum D mean , V 65Gy , V 75Gy , anus D mean , and bladder D mean , the difference between predicted and achieved was within 0.4 Gy or 0.3% (SD within 1.8 Gy or 1.3%). Thirteen detected outliers were re-planned, leading to moderate but statistically significant improvements (mean, max): rectum D mean (1.3 Gy, 3.4 Gy), V 65Gy (2.7%, 4.2%), anus D mean (1.6 Gy, 6.9 Gy), and bladder D mean (1.5 Gy, 5.1 Gy). The rectum V 75Gy of the new plans slightly increased (0.2%, p = 0.087). A high accuracy DVH prediction tool was developed and used for independent QA of automatically generated plans. In 28% of plans, minor dosimetric deviations were observed that could be improved by plan adjustments. Larger gains are expected for manually generated plans. Copyright © 2017 Elsevier B.V. All rights reserved.

Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2–harboring clones as main relapse-driving force in childhood ALL

PubMed Central

Morak, Maria; Attarbaschi, Andishe; Fischer, Susanna; Nassimbeni, Christine; Grausenburger, Reinhard; Bastelberger, Stephan; Krentz, Stefanie; Cario, Gunnar; Kasper, David; Schmitt, Klaus; Russell, Lisa J.; Pötschger, Ulrike; Stanulla, Martin; Eckert, Conny; Mann, Georg; Haas, Oskar A.; Panzer-Grümayer, Renate

2014-01-01

The P2RY8-CRLF2 fusion defines a particular relapse-prone subset of childhood acute lymphoblastic leukemia (ALL) in Italian Association of Pediatric Hematology and Oncology Berlin-Frankfurt-Münster (AIEOP-BFM) 2000 protocols. To investigate whether and to what extent different clone sizes influence disease and relapse development, we quantified the genomic P2RY8-CRLF2 fusion product and correlated it with the corresponding CRLF2 expression levels in patients enrolled in the BFM-ALL 2000 protocol in Austria. Of 268 cases without recurrent chromosomal translocations and high hyperdiploidy, representing approximately 50% of all cases, 67 (25%) were P2RY8-CRLF2 positive. The respective clone sizes were ≥ 20% in 27% and < 20% in 73% of them. The cumulative incidence of relapse of the entire fusion-positive group was clone size independent and significantly higher than that of the fusion-negative group (35% ± 8% vs 13% ± 3%, P = .008) and primarily confined to the non–high-risk group. Of 22 P2RY8-CRLF2–positive diagnosis/relapse pairs, only 4/8 had the fusion-positive dominant clone conserved at relapse, whereas none of the original 14 fusion-positive small clones reappeared as the dominant relapse clone. We conclude that the majority of P2RY8-CRLF2–positive clones are small at diagnosis and virtually never generate a dominant relapse clone. Our findings therefore suggest that P2RY8-CRLF2–positive clones do not have the necessary proliferative or selective advantage to evolve into a disease-relevant relapse clone. PMID:23091296

Animal models of fear relapse.

PubMed

Goode, Travis D; Maren, Stephen

2014-01-01

Whereas fear memories are rapidly acquired and enduring over time, extinction memories are slow to form and are susceptible to disruption. Consequently, behavioral therapies that involve extinction learning (e.g., exposure therapy) often produce only temporary suppression of fear and anxiety. This review focuses on the factors that are known to influence the relapse of extinguished fear. Several phenomena associated with the return of fear after extinction are discussed, including renewal, spontaneous recovery, reacquisition, and reinstatement. Additionally, this review describes recent work, which has focused on the role of psychological stress in the relapse of extinguished fear. Recent developments in behavioral and pharmacological research are examined in light of treatment of pathological fear in humans. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Exploring the factors influencing relapse and recovery among drug and alcohol addicted women.

PubMed

Snow, D; Anderson, C

2000-07-01

1. Both women who were in treatment for relapse to and in sustained recovery from drugs and alcohol had multiple co-occurring addictions such as relationship, spending, food, and shopping that complicated the recovery process. 2. Depression is a major trigger for relapse in women with alcohol and drug problems. Recognition and treatment of depression is critical to achieve successful outcomes of treatment for these women, and teaching them to monitor their mood changes and seek help will improve the chances of preventing relapse. 3. Subjects in neither the relapse nor recovery sample recognized the significant influence of current violent partnerships or the ending of a violent relationship on their relapse or recovery.

New concepts for the old challenge of African relapsing fever borreliosis.

PubMed

Cutler, S J; Abdissa, A; Trape, J-F

2009-05-01

Relapsing fever, caused by spirochaetes belonging to the genus Borrelia, was once the cause of worldwide epidemic disease. This was largely through infection with the louse-borne form of the disease, caused by Borrelia recurrentis (louse-borne relapsing fever (LBRF)). During the last century, we have witnessed the demise of this infection, largely owing to improved standards of living and the introduction of the insecticide DDT, resulting in a reduction in the incidence of the body louse, the vector for relapsing fever. In areas of extreme poverty this disease persists, causing a significant burden of disease. It is now looking probable that this infection is caused by a louse-adapted variant of Borrelia duttonii, transmitted by Ornithodoros moubata 'soft' ticks in East Africa. Like LBRF, infection still causes impact, particularly affecting young children and pregnant women. Over recent years, the true burden of relapsing fever caused by infection with the closely related Borrelia crocidurae, transmitted by Ornithodoros sonrai ticks, has only just begun to emerge. Here, the current state of knowledge concerning relapsing fever in Africa is reviewed.

[Study on the social factors of patients with genital herpes relapsing].

PubMed

Liu, Ji-Feng; Xu, Ai-E; Li, Yong-Wei; Zhang, Di-Min

2006-05-01

To investigate the social factors of patients with genital herpes (GH) relapsing and guide GH patients to avoid the related social factors. To select 96 case of patients with recurrent genital herpes of final diagnosis and detailedly record the related social factors before relapsing. The social factors were compared between male and female GH patients, and compared between frequently recurrent (> 6/year) and non-frequently recurrent GH patients (< or = 6/year) too. 65.6% (63/96) of recurrent GH patients have certain social factors before relapsing. The main social factors are overtiredness, mental stress and excessive sexual contact. Staying up late and excessive drinking are common social factors, too. There was no significant difference of social factors between male and female GH patients (P >. 05), and also no significant difference between frequently recurrent and non-frequently recurrent GH patients (P > 0.05), too. Overtiredness, mental stress and excessive sexual are the main social elements during inducing genital herpes relapsing. It is important to reduce GH relapsing and spreading of HIV and syphilis by guiding recurrent genital herpes patients to avoid related social elements.

Isolated CNS relapse following stem cell transplantation for juvenile myelomonocytic leukemia.

PubMed

Wilson, David B; Michalski, Jeff M; Grossman, William J; Hayashi, Robert J

2003-11-01

A 1-year-old girl with juvenile myelomonocytic leukemia (JMML) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. A few months after BMT she experienced a bone marrow relapse that did not respond to withdrawal of immunosuppression. To enhance the graft-versus-leukemia (GVL) effect, she underwent peripheral stem cell transplantation (PSCT) from the same donor, using a nonmyeloablative conditioning regimen. She achieved clinical remission and developed chronic graft-versus-host disease (GVHD), which was treated with prednisone and cyclosporine A. One year after PSCT she experienced an isolated central nervous system (CNS) relapse. She was treated with intrathecal Ara-C followed by craniospinal irradiation and achieved a third clinical remission. While extramedullary relapses have been described in JMML, this is the first report of a CNS relapse. Based on this case and others in the literature, the authors suggest that newer therapies are changing the natural history of JMML. By manipulating the GVL effect it is possible to achieve a prolonged bone marrow remission, but only at the expense of unmasking the risk of late extramedullary relapse.

Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma.

PubMed

Illhardt, Toni; Toporski, Jacek; Feuchtinger, Tobias; Turkiewicz, Dominik; Teltschik, Heiko-Manuel; Ebinger, Martin; Schwarze, Carl-Philipp; Holzer, Ursula; Lode, Holger N; Albert, Michael H; Gruhn, Bernd; Urban, Christian; Dykes, Josefina H; Teuffel, Oliver; Schumm, Michael; Handgretinger, Rupert; Lang, Peter

2018-05-01

Pediatric patients with refractory or relapsed metastatic neuroblastoma (NBL) have a poor prognosis despite autologous stem cell transplantation (SCT). Allogeneic SCT from a haploidentical donor has a remarkable alloreactive effect in patients with leukemia; thus, we evaluated this approach in children with very high-risk NBL. We analyzed data from 2 prospective phase I/II trials. A total of 26 patients with refractory (n = 5), metastatic relapsed (n = 20), or locally relapsed MYCN-positive (n = 1) NBL received a median of 17 × 10 6 /kg T/B cell-depleted CD34 + stem cells with 68 × 10 3 /kg residual T cells and 107 × 10 6 /kg natural killer cells. The conditioning regimen comprised melphalan, fludarabine, thiotepa, OKT3, and a short course of mycophenolate mofetil post-transplantation. Engraftment occurred in 96% of the patients. Event-free survival and overall survival at 5 years were 19% and 23%, respectively. No transplantation-related mortality was observed, and the single death was due to progression/subsequent relapse. The median duration of follow-up was 8.1 years. Patients in complete remission before SCT had a significantly better prognosis than those with residual tumor load (P < .01). All patients with progressive disease before SCT relapsed within 1 year. Grade II and grade III acute graft-versus-host disease (GVHD) occurred in 31% and 12% of the patients, respectively. Chronic limited and extensive GVHD occurred in 28% and 10%, respectively. Our data indicate that haploidentical SCT is a feasible treatment option that can induce long-term remission in some patients with NBL with tolerable side effects, and may enable the development of further post-transplantation therapeutic strategies based on the donor-derived immune system. Copyright © 2018. Published by Elsevier Inc.

Family History and Relapse in Pediatric Acute Myeloid Leukemia.

PubMed

Mehrvar, Azim; Tashvighi, Maryam; Faranoush, Mohammad; Reinhardt, Dirk; Niktoreh Mofrad, Naghmeh; Hedayati Asl, Amir Abbas; Alebouyeh, Mardawij

2015-12-01

We report the epidemiology and characteristics of acute myeloid leukemia and outcomes of its treatment with the AML-BFM 83 protocol at the Mahak Pediatric Cancer Treatment and Research Center, Tehran, Iran, from 2007 to 2012. A positive family history of cancer or leukemia was associated with the risk of relapse (family history of cancer in relapse: n = 11; 61%, P = 0.136, leukemia: n = 7; 39%; P = 0.016). Treatment-related mortality was 19% and associated with underweight patients (n = 5; 62.5%; P = 0.158). Event-free and overall survivals were 36% (SE = 3.5) and 44% (SE = 3.4), respectively. These data suggest a possible relationship between family history and relapse rate. © 2015 Wiley Periodicals, Inc.

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.

[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.

Neurogentics of Dopaminergic Receptor Super-sensitivity in Activation of Brain Reward Circuitry and Relapse: Proposing “Deprivation-Amplification Relapse Therapy” (DART)

PubMed Central

Downs, B. William; Bowirrat, Abdalla; Waite, Roger L.; Braverman, Eric R.; Madigan, Margaret; Oscar-Berman, Marlene; DiNubile, Nicholas; Gold, Mark

2013-01-01

Background and Hypothesis It is well known that after prolonged abstinence, individuals who imbibe or use their drug of choice experience a powerful euphoria that precipitates serious relapse. While a biological explanation for this conundrum has remained elusive, we hypothesize that this clinically observed “super sensitivity” might be tied to genetic dopaminergic polymorphisms. Another therapeutic conundrum relates to the paradoxical finding that the dopaminergic agonist bromocriptine induces stronger activation of brain reward circuitry in individuals who carry the DRD2 A1 allele compared to DRD2 A2 allele carriers. Based upon the fact that carriers of the A1 allele relative to the A2 allele of the DRD2 gene have significantly lower D2 receptor density, a reduced sensitivity to dopamine agonist activity would be expected in the former. Thus, it is perplexing that with low D2 density there is an increase in reward sensitivity with the dopamine agonist bromocriptine. Moreover, under chronic or long-term therapy, the potential proliferation of D2 receptors with bromocriptine has been shown in vitro. This seems to lead to a positive outcome and significantly better treatment compliance only in A1 carriers. Proposal and Conclusion We propose that low D2 receptor density and polymorphisms of the D2 gene are associated with risk for relapse of substance abuse including alcohol dependence, heroin craving, cocaine dependence, methamphetamine abuse, nicotine sensitization, and glucose craving. With this in mind, we suggest a putative physiological mechanism that may help to explain the enhanced sensitivity following intense acute dopaminergic D2 receptor activation: “denervation supersensitivity.” Thus, the administration of dopamine D2 agonists would target D2 sensitization and attenuate relapse, especially in D2 receptor A1 allele carriers. This hypothesized mechanism is supported by clinical trials utilizing the amino-acid neurotransmitter precursors

Treatment of multiple sclerosis relapses with high-dose methylprednisolone reduces the evolution of contrast-enhancing lesions into persistent black holes.

PubMed

Di Gregorio, Maria; Gaetani, Lorenzo; Eusebi, Paolo; Floridi, Piero; Picchioni, Antonella; Rosi, Giovanni; Mancini, Andrea; Floridi, Chiara; Baschieri, Francesca; Gentili, Lucia; Sarchielli, Paola; Calabresi, Paolo; Di Filippo, Massimiliano

2018-03-01

The MRI evidence of persistent black holes (pBHs) on T1-weighted images reflects brain tissue loss in multiple sclerosis (MS). The evolution of contrast-enhancing lesions (CELs) into pBHs probably depends on the degree and persistence of focal brain inflammation. The aim of our retrospective study was to evaluate the effect of a single cycle of intravenous methylprednisolone (IVMP), as for MS relapse treatment, on the risk of CELs' evolution into pBHs. We selected 57 patients with CELs on the baseline MRI scan. We evaluated the evolution of CELs into pBHs on a follow-up MRI scan performed after ≥ 6 months in patients exposed and not exposed to IVMP for the treatment of relapse after the baseline MRI. In our cohort, 182 CELs were identified in the baseline MRI and 57 of them (31.3%) evolved into pBHs. In the multivariate analysis, the exposure of CELs to IVMP resulted to be a significant independent protective factor against pBHs' formation (OR 0.28, 95% CI 0.11-0.766, p = 0.005), while ring enhancement pattern and the fact of being symptomatic were significant risk factors for CELs' conversion into pBHs (OR 6.42, 95% CI 2.55-17.27, p < 0.001 and OR 13.19, 95% CI 1.56-288.87, p = 0.037). The exposure of CELs to a cycle of IVMP as for relapse treatment is associated with a lower risk of CELs' evolution into pBHs. Future studies are required to confirm the potential independent protective effect of IVMP on CELs' evolution into pBHs.

Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco

PubMed Central

2011-01-01

Background Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high. Methods Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse. Results 291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2

Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco.

PubMed

Dooley, Kelly E; Lahlou, Ouafae; Ghali, Iraqi; Knudsen, Janine; Elmessaoudi, My Driss; Cherkaoui, Imad; El Aouad, Rajae

2011-02-28

Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high. Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse. 291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1

A phase I trial of Flavopiridol in relapsed multiple myeloma

PubMed Central

Hofmeister, Craig C.; Poi, Ming; Bowers, Mindy A.; Zhao, Weiqiang; Phelps, Mitch A.; Benson, Don M.; Kraut, Eric H.; Farag, Sherif; Efebera, Yvonne A.; Sexton, Jennifer; Lin, Thomas S.; Grever, Michael; Byrd, John C.

2014-01-01

Purpose Flavopiridol is primarily a cyclin-dependent kinase (CDK)-9 inhibitor and we performed a dose escalation trial to determine the maximum tolerated dose, safety, and generate a pharmacokinetic profile. Methods Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus then continuous infusion weekly for 4 weeks in a 6 week cycle. Results Fifteen patients were treated at three dose levels (30 mg/m2 bolus, 30 mg/m2 CIV to 50 mg/m2 bolus, 50 mg/m2 CIV). Cytopenias were significant and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients, grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein greater than 50% percent that did not persist. Pharmacokinetic properties were similar to prior publications and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. Conclusions Flavopiridol as a single agent given by bolus then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723). PMID:24241210

Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group.

PubMed

Laubach, J; Garderet, L; Mahindra, A; Gahrton, G; Caers, J; Sezer, O; Voorhees, P; Leleu, X; Johnsen, H E; Streetly, M; Jurczyszyn, A; Ludwig, H; Mellqvist, U-H; Chng, W-J; Pilarski, L; Einsele, H; Hou, J; Turesson, I; Zamagni, E; Chim, C S; Mazumder, A; Westin, J; Lu, J; Reiman, T; Kristinsson, S; Joshua, D; Roussel, M; O'Gorman, P; Terpos, E; McCarthy, P; Dimopoulos, M; Moreau, P; Orlowski, R Z; Miguel, J S; Anderson, K C; Palumbo, A; Kumar, S; Rajkumar, V; Durie, B; Richardson, P G

2016-05-01

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

Does Feedback-Related Brain Response during Reinforcement Learning Predict Socio-motivational (In-)dependence in Adolescence?

PubMed Central

Raufelder, Diana; Boehme, Rebecca; Romund, Lydia; Golde, Sabrina; Lorenz, Robert C.; Gleich, Tobias; Beck, Anne

2016-01-01

This multi-methodological study applied functional magnetic resonance imaging to investigate neural activation in a group of adolescent students (N = 88) during a probabilistic reinforcement learning task. We related patterns of emerging brain activity and individual learning rates to socio-motivational (in-)dependence manifested in four different motivation types (MTs): (1) peer-dependent MT, (2) teacher-dependent MT, (3) peer-and-teacher-dependent MT, (4) peer-and-teacher-independent MT. A multinomial regression analysis revealed that the individual learning rate predicts students’ membership to the independent MT, or the peer-and-teacher-dependent MT. Additionally, the striatum, a brain region associated with behavioral adaptation and flexibility, showed increased learning-related activation in students with motivational independence. Moreover, the prefrontal cortex, which is involved in behavioral control, was more active in students of the peer-and-teacher-dependent MT. Overall, this study offers new insights into the interplay of motivation and learning with (1) a focus on inter-individual differences in the role of peers and teachers as source of students’ individual motivation and (2) its potential neurobiological basis. PMID:27199873

Cytokine production profiles in chronic relapsing-remitting experimental autoimmune encephalomyelitis: IFN-γ and TNF-α are important participants in the first attack but not in the relapse.

PubMed

Hidaka, Yoshihiko; Inaba, Yuji; Matsuda, Kazuyuki; Itoh, Makoto; Kaneyama, Tomoki; Nakazawa, Yozo; Koh, Chang-Sung; Ichikawa, Motoki

2014-05-15

Multiple sclerosis (MS) is a chronic demyelinating disease often displaying a relapsing-remitting course of neurological manifestations that is mimicked by experimental autoimmune encephalomyelitis (EAE) in animal models of MS. In particular, NOD mice immunized with myelin oligodendrocyte glycoprotein peptide 35-55 develop chronic relapsing-remitting EAE (CREAE). To elucidate the mechanisms that cause MS relapse, we investigated the histopathology and cytokine production of spleen cells and mRNA expression levels in the central nervous system (CNS) of CREAE mice. During the first attack, inflammatory cell infiltration around small vessels and in the subarachnoid space was observed in the spinal cord. Spleen cell production and mRNA expression in the CNS of several cytokines, including IFN-γ, TNF-α, IL-6, IL-17, and CC chemokine ligand 2 (CCL2), were higher in CREAE mice than in controls. Afterwards, parenchymal infiltration and demyelination were observed histologically in the spinal cord and corresponded with the more severe clinical symptoms of the first and second relapses. IL-17 and CCL2, but not IFN-γ, TNF-α, or IL-6, were also produced by spleen cells during recurrences. Our results suggested that the immune mechanisms in relapses were different from those in the first attack for CREAE. Further investigation of CREAE mechanisms may provide important insights into successful therapies for human relapsing-remitting MS. Copyright © 2014 Elsevier B.V. All rights reserved.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L J; Vellekoop, L; Thomson, S; Stewart, D; Hester, J P; McCredie, K B

1979-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%), when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Autologous bone marrow transplantation in relapsed adult acute leukemia.

PubMed

Dicke, K A; Zander, A R; Spitzer, G; Verma, D S; Peters, L; Vellekoop, L; Thomson, S; Stewart, D; McCredie, K B

1980-01-01

From March, 1976 to February, 1979, 28 cases of adult acute leukemia of which 24 were evaluable were treated in irreversible relapse with high dose chemotherapy (piperazinedione) and supra-lethal total body irradiation (TBI) in conjunction with autologous bone marrow transplantation (ABMT). The marrow cells grafted were collected and stored in liquid nitrogen at the time of remission. In 12 patients the marrow cells were fractionated using discontinuous albumin gradients in an attempt to separate normal cells from residual leukemic cells. Twelve patients achieved complete remission (CR); in 9 additional patients signs of engraftment were evident but death occurred before achievement of CR. Seven of 12 AML patients, which were treated with bone marrow transplantation as first treatment of their relapse, achieved CR. Four of 5 patients with ALL, whose bone marrows were collected during first remission, reached CR. The median CR duration was 4+ months and the median survival of the patients reaching CR was 6+ months. Autologous bone marrow transplantation offers a good chance of CR (66%) when marrow is collected during first remission and used as first treatment for AML in third relapse and ALL in second relapse.

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

PubMed

Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V

2015-02-01

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

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

treatment of RRMS are predicted to be partially offset by reduced costs of relapses in the Canadian healthcare system.

Cortico-Amygdala Coupling as a Marker of Early Relapse Risk in Cocaine-Addicted Individuals

PubMed Central

McHugh, Meredith J.; Demers, Catherine H.; Salmeron, Betty Jo; Devous, Michael D.; Stein, Elliot A.; Adinoff, Bryon

2014-01-01

Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting-state functional connectivity (rsFC) in neural circuits arising from the amygdala, a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state functional magnetic resonance imaging connectivity (6 min) was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry, separate seeds were derived for the left and right basolateral (BLA) and corticomedial (CMA) amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive-Compulsive Cocaine Use Scale and Personality Inventory. Relapse within the first 30 days post-treatment (n = 24) was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC) relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21). Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus) compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes. PMID

Cigarette smoking as an expression of independence and freedom among inmates in a tobacco-free prison in the United States.

PubMed

van den Berg, Jacob J; Bock, Beth; Roberts, Mary B; Stein, Lynda A R; Friedmann, Peter D; Martin, Stephen A; Clarke, Jennifer G

2014-02-01

Most adults report initiation of cigarette smoking during adolescence, a time also marked by developmental striving for independence and freedom. Tobacco use may retain its association with independence and/or freedom into adulthood. This association may contribute to continued tobacco use and/or increased risk of relapse to smoking among some individuals. This study examines the relationship between cigarette smoking and perceptions of independence and freedom among inmates in a tobacco-free prison in the northeastern United States. Questionnaires administered to 247 male and female inmates 6 weeks prior to scheduled prison release assessed demographics, smoking history, nicotine dependence, attitudes toward smoking, and plans for tobacco use or abstinence after prison release. Perceptions of smoking as an expression of independence and freedom were measured using 2 items. Smoking was assessed 3 weeks postrelease. Constructs of freedom and independence were correlated but did not overlap completely. Both constructs were negatively associated with plans for smoking abstinence after prison release, and with perceived costs of continued smoking. Number of cigarettes smoked postrelease and perception of the pros of smoking were associated with freedom, but not independence. Associations of smoking as an expression of freedom and independence may negatively influence plans for renewed smoking after a forced abstinence. Additional research is needed to determine the degree to which these 2 constructs predict smoking behavior and whether they can be used to improve interventions for incarcerated smokers.

Cigarette Smoking as an Expression of Independence and Freedom Among Inmates in a Tobacco-Free Prison in the United States

PubMed Central

2014-01-01

Introduction: Most adults report initiation of cigarette smoking during adolescence, a time also marked by developmental striving for independence and freedom. Tobacco use may retain its association with independence and/or freedom into adulthood. This association may contribute to continued tobacco use and/or increased risk of relapse to smoking among some individuals. This study examines the relationship between cigarette smoking and perceptions of independence and freedom among inmates in a tobacco-free prison in the northeastern United States. Methods: Questionnaires administered to 247 male and female inmates 6 weeks prior to scheduled prison release assessed demographics, smoking history, nicotine dependence, attitudes toward smoking, and plans for tobacco use or abstinence after prison release. Perceptions of smoking as an expression of independence and freedom were measured using 2 items. Smoking was assessed 3 weeks postrelease. Results: Constructs of freedom and independence were correlated but did not overlap completely. Both constructs were negatively associated with plans for smoking abstinence after prison release, and with perceived costs of continued smoking. Number of cigarettes smoked postrelease and perception of the pros of smoking were associated with freedom, but not independence. Conclusions: Associations of smoking as an expression of freedom and independence may negatively influence plans for renewed smoking after a forced abstinence. Additional research is needed to determine the degree to which these 2 constructs predict smoking behavior and whether they can be used to improve interventions for incarcerated smokers. PMID:24151140

Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

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

Kim, Ji Hyun; Stein, Anthony; Tsai, Nicole

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph nodemore » chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.« less

Effects of Nicotine Fading and Relapse Prevention on Smoking Cessation.

ERIC Educational Resources Information Center

Brown, Richard A.; And Others

1984-01-01

Conducted a pilot study which combined nicotine-fading and relapse prevention with smokers (N=30) and compared this program to conditions where subjects (N=46) received nicotine-fading or relapse prevention only. Results showed no difference among groups in abstinence or rate at any follow-up point. (LLL)

Relapse Prevention for Alcohol and Drug Problems: That Was Zen, This Is Tao

ERIC Educational Resources Information Center

Witkiewitz, Katie; Marlatt, Alan G.

2004-01-01

Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the…

Negative affect subtypes and craving differentially predict long-term cessation success among smokers achieving initial abstinence.

PubMed

Zuo, Yantao; Rabinovich, Norka E; Gilbert, David G

2017-03-01

This study aimed to examine the associations of individual trajectories of three types of negative affect (NA: anxiety, depression, and anger) and craving during a 44-day period of incentivized smoking abstinence period with cessation outcome at 3 months and at 1 year. Adult smokers (N = 140) completed questionnaire assessments of NA and craving during pre-quit baseline sessions and 15 postquit sessions over the 45 days of biochemically verified abstinence while on nicotine or placebo patch treatment. Growth curve and logistic regression analyses were used to examine the associations of trajectory parameters of the individual NA states and craving with the abstinence outcomes at 3 months and 1 year postquit. Greater declines in anxiety, depression, and anger symptoms over the first 44 days of smoking cessation were predictive of higher odds of abstinence at both 3 months and 1 year. Moreover, the greater declines in anxiety and anger remained as significant predictors of abstinence at both time points, independent of the predictive ability of the trajectory profiles of craving. The findings suggest that slower dissipation of NA, especially anxiety and anger, represents a greater risk for relapse to smoking beyond that predicted by craving during early abstinence. Thus, temporal profiles of the affective symptoms convey unique motivational significance in relapse. Reduction in NA during early abstinence may be a valid target for interventions to increase long-term cessation success rates particularly among individuals with refractory affective symptoms.

Length of stay of stroke rehabilitation inpatients: prediction through the functional independence measure.

PubMed

Franchignoni, F; Tesio, L; Martino, M T; Benevolo, E; Castagna, M

1998-01-01

A model for prediction of length of stay (LOS, in days) of stroke rehabilitation inpatients was developed, based on patients' age (years) and function at admission (scored on the Functional Independence Measure, FIMSM). One hundred and twenty-nine cases, consecutively admitted to three free-standing rehabilitation centres in Italy, were analyzed. A multiple linear regression using forward stepwise selection procedure was adopted. Median admission and discharge scores were: 57 and 75 for the total FIM score, 29 and 48 for the 13-item motor FIM subscore, 29 and 30 for the 5-item cognitive FIM subscore (potential range: 18-126, 13-91, 5-35, respectively). Median LOS was 44 days (interquartile range 30-62). The logLOS predictive model included three FIM items ("toilet transfer", TTr; "social interaction"; "expression") and patient's age (R2 = 0.48). TTr alone explained 31.3% of the variance of logLOS. These results are consistent with previous American studies, showing that FIM scores at admission are strong predictors of patients' LOS, with the transfer items having the greatest predictive power.

Impact of Life Events on the Relapse of Schizophrenic Patients

ERIC Educational Resources Information Center

Hussein, Hassan Ali; Jacoob, Shirooq; Sharour, Loai Abu

2016-01-01

Objectives: To investigate the relationship between stressful life events at the time of relapse in schizophrenic patients at psychiatric hospitals in Baghdad city. Methodology: A purposive (non-probability) sampling of 50 schizophrenic patients who have relapsed was involved in the present study. Data were collected through the use of the…

Survival outcomes of patients with germ cell tumors treated with high-dose chemotherapy for refractory or relapsing disease.

PubMed

Zschäbitz, Stefanie; Distler, Florian A; Krieger, Benjamin; Wuchter, Patrick; Schäfer-Eckart, Kerstin; Jenzer, Maximilian; Hohenfellner, Markus; Dreger, Peter; Haag, Georg Martin; Jäger, Dirk; Pahernik, Sascha; Grüllich, Carsten

2018-04-27

Male patients with metastatic germ cell tumors can be cured in up to 96% of cases depending on stage and IGCCCG prognosis group. Treatment in relapse consists of conventional or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) combined with local treatment modalities. Most patients were classified as poor risk according to IGCCCG ( n = 24; 52%) and as intermediate ( n = 12), high ( n = 16), or very high risk ( n = 9) at time of first relapse according to IPFSG criteria. In 67% of patients ( n = 31) HDCT/ASCT was performed as first salvage treatment in relapse or for primary refractory disease following first line chemotherapy. In 46% of patients ( n = 21) progressive disease was documented after mobilization and prior to HDCT/ASCT. Median progression free survival (mPFS) was 7.4 months (95% confidence interval (CI): 1.3-13.6) while median overall survival (mOS) was 22.2 months (95% CI: 8.9-35.5). When stratified for IPFSG risk group, mPFS ( p < 0.001) and mOS ( p = 0.009) differed significantly between risk groups (very low vs. low vs. intermediate vs. high vs. very high). Metastases to liver/bone/brain and platinum refractory disease were independent risk factors for inferior PFS ( p = 0.024; p = 0.008) but not OS. Forty-six patients treated with HDCT/ASCT at the university clinics in Heidelberg and Nuremberg between 2000-2016 were identified and analyzed. Data was collected retrospectively. HDCT/ASCT offers a potential curative strategy for patients with relapsed GCT. Improvement is still needed in patients with intermediate, high, and very high IPFSG risk group.

A prevalence study of urinary tract infections in acute relapse of schizophrenia.

PubMed

Miller, Brian J; Graham, Krystle L; Bodenheimer, Chelsea M; Culpepper, Nick H; Waller, Jennifer L; Buckley, Peter F

2013-03-01

Schizophrenia is associated with immune abnormalities and increased mortality from infectious diseases. The aim of this study was to examine whether acute relapse of schizophrenia was associated with urinary tract infection (UTI), in comparison with controls, after controlling for potential confounding factors. In a prevalence study conducted from January 2010 to April 2012 at Georgia Health Sciences University Medical Center, Augusta, we recruited 136 adult subjects (mean age = 42.8 years): 57 inpatients with an acute relapse of DSM-IV schizophrenia, 40 stable outpatients with DSM-IV schizophrenia, and 39 healthy controls from the community. Urinary tract infection was defined as having positive leukocyte esterase and/or positive nitrites on urinalysis and having ≥ 5 leukocytes per high-powered field (implies 5-10 or more) on urine microscopy. Determination of UTI status was made for each subject, and analyses were performed to examine the association between UTI and acute relapse of schizophrenia. 35% of acutely relapsed subjects, versus 5% of stable outpatients and 3% of controls, had a UTI (P < .001). Only 40% of subjects in the acute relapse group classified as having a UTI were treated with antibiotics during hospitalization. After analyses were controlled for gender and smoking status, subjects in the acute relapse group were almost 29 times more likely to have a UTI than controls (odds ratio = 28.97; 95% CI, 3.44-243.85; P = .002). There was no statistically significant association with UTI among the stable outpatients versus controls. Our finding of an association between an increased prevalence of UTI and acute psychotic relapse warrants replication in other samples. The mechanism of this association remains unclear. The results also highlight the potential importance of monitoring for comorbid UTI in acutely relapsed patients with schizophrenia. © Copyright 2013 Physicians Postgraduate Press, Inc.

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

PubMed

Gueneau, Pauline; Chretien, Marie-Lorraine; Cransac-Miet, Amelie; Aho, Ludwig Serge; Lafon, Ingrid; Favennec, Camille; Guy, Julien; Caillot, Denis; Boulin, Mathieu

2018-05-01

To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10 -3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A simple technique for correction of relapsed overjet.

PubMed

Kakkirala, Neelima; Saxena, Ruchi

2014-01-01

Class III malocclusions are usually growth related discrepancies, which often become more severe when growth is completed Orthognathic surgery can be a part of the treatment plan, although a good number of cases can be treated non-surgically by camouflage treatment. The purpose of this report is to review the relapse tendency in patients treated non-surgically. A simple technique is described to combat one such post-treatment relapse condition in an adult patient who had undergone orthodontic treatment by extraction of a single lower incisor.

Dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

PubMed

Lehmann-Che, Jacqueline; Bally, Cécile; Letouzé, Eric; Berthier, Caroline; Yuan, Hao; Jollivet, Florence; Ades, Lionel; Cassinat, Bruno; Hirsch, Pierre; Pigneux, Arnaud; Mozziconacci, Marie-Joelle; Kogan, Scott; Fenaux, Pierre; de Thé, Hugues

2018-05-24

Retinoic acid (RA) and arsenic target the t(15;17)(q24;q21) PML/RARA driver of acute promyelocytic leukemia (APL), their combination now curing over 95% patients. We report exome sequencing of 64 matched samples collected from patients at initial diagnosis, during remission, and following relapse after historical combined RA-chemotherapy treatments. A first subgroup presents a high incidence of additional oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that these relapses derive from ancestral pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.

Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia