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PubMed1987

Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats.

Rats with experimental allergic encephalomyelitis (EAE) develop paralysis, from which most of them recover. It has been hypothesized that spontaneous remission in EAE is due to the stress of paralysis and the subsequent hypersecretion of endogenous immunosuppressive adrenal glucocorticoids. Spontaneous relapse after a remission is thought to occur when the stress of paralysis and the adrenal response to it are terminated. In the present work, this theory has been tested in a newly developed relapsing form of EAE in rats. After an initial attack characterized by paralysis, the control rats had a remission and then a second episode of paralysis (relapse). In contrast, rats subjected to restraint during the remission period were protected from relapses. Injections of adrenal glucocorticoids during the remission had a similar protective effect. These findings support the hypothesis that remissions and relapses in EAE are caused by the occurrence and subsequent disappearance of the adrenals' immunosuppressive response to the stress of paralysis, because the addition of stress during the period of remission maintained the adrenals' hyperactive state and thereby prevented relapses.

Adrenal Glands↗

PubMed1988

A long-term prospective evaluation of the circumferential supracrestal fiberotomy in alleviating orthodontic relapse.

This prospective study conducted during a period of nearly 15 years initially involved 320 consecutively selected cases. The primary purpose of the investigation was to statistically evaluate the efficacy of the circumferential supracrestal fiberotomy (CSF) procedure in alleviating dental relapse following orthodontic treatment. The "Irregularity Index" method of Little for measuring the malposition of teeth was used to quantitatively record the relapse of the control and CSF cases at approximately 4 to 6 years after active treatment and again at 12 to 14 years after active treatment. The differences between the mean relapses of the control and the CSF cases were highly significant at both time intervals. The surgical procedure appeared to be somewhat more effective in alleviating pure rotational relapse than in labiolingual relapse. On a long-term basis, the CSF procedure was shown to be more successful in reducing relapse in the maxillary anterior segment than in the mandibular anterior segment. Nevertheless, a significant and unpredictable variation in individual tooth movement following orthodontic treatment was observed in both the control and CSF groups. No clinically significant increase in the periodontal sulcus depth nor decrease in the labially attached gingiva of the CSF teeth was observed at 1 and 6 months following the surgical procedure.

Adolescent↗

PubMed1991

The nature of Class II relapse after Herbst appliance treatment: a cephalometric long-term investigation.

The purpose of this investigation was to assess the number of, and the interrelation between, skeletal and dental components that contribute to Class II relapse after Herbst treatment. A comparison was made between 15 relapse and 14 stable cases at least 5 years after treatment. Lateral cephalograms taken before and immediately after Herbst treatment, as well as 6 months and 5 to 10 years after treatment, were analyzed. The results revealed that relapse in the overjet and sagittal molar relationship resulted mainly from posttreatment maxillary and mandibular dental changes. In particular, the maxillary incisors and molars moved significantly (p less than 0.05) to a more anterior position in the relapse group than in the stable group. The interrelation between maxillary and mandibular posttreatment growth was favorable and did not contribute to the occlusal relapse. It is hypothesized that the main causes of the Class II relapse in patients treated with the Herbst appliance were a persisting lip-tongue dysfunction habit and an unstable cuspal interdigitation after treatment.

Adolescent↗

PubMed1995

Social settings and addiction relapse.

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.

Adult↗

PubMed2004

A randomised trial of early warning signs relapse prevention training in the treatment of alcohol dependence.

A pragmatic randomised trial examined the effects of Early Warning Signs Relapse Prevention Training (EWSRPT) on drinking in alcohol dependent persons with history of relapse. Participants were 124 abstinent alcohol dependent patients with a history of relapse (median five relapses) who entered the trial as they completed a 6-week day treatment programme. They were randomly allocated to receive either (1) Aftercare as Usual (AU) or (2) AU plus 15 individual sessions of EWSRPT using Gorski's protocol. Assessment carried out at entry to the trial, and 4, 8, and 12 months later, included self-report of drinking, blood tests (gamma glutamyl transferase, GGT; serum alanine aminotransferase, ALT) and measures of functioning (Alcohol Problems Questionnaire, APQ; SF36, Brief Symptom Inventory, BSI; Assessment of Warning-signs of Relapse, AWARE). Intention to treat analysis found no significant differences in continuous abstinence during the follow-up year (17% of 58 AU, 31% of 58 EWSRPT, p=0.08). The EWSRPT participants had a significantly lower probability of drinking heavily (74% of AU, 55% of EWSRPT, p=0.04), and significantly fewer days drinking (p=0.05) and heavy drinking (p=0.04). These clinically worthwhile effects for a relapse-prone group justify further research into EWSRPT.

Adult↗

PubMed2005

Can transtheoretical model measures predict relapse from the action stage of change among ex-smokers who quit after calling a quitline?

This study explored whether transtheoretical model (TTM) measures could predict relapse from the action stage, i.e., during the first 6 months of smoking cessation. Predictors of relapse were examined between time 2 (3-month) and time 3 (6-month) assessments (n = 247), and also between time 3 (6-month) and time 4 (12-month) assessments (n = 204). Consistent predictors of relapse included lower self-efficacy and determination to quit and higher temptations to smoke. Some predictors of relapse changed according to how long a person had already been quit for. Contrary to the TTM, greater behavioral change process use predicted relapse among people who had already quit for less than a month, and did not prevent relapse among those who had already quit for a month or more between time 2 and time 3. Cross-sectional analyses showed significant decreases in temptations to smoke and in the use of some of the change processes, which stabilised at about 1 month post-cessation. The findings suggest that there may be a stage boundary at around 1 month post-cessation, and question the homogeneity, and hence validity, of the TTM-defined action stage of change.

Adolescent↗

PubMed2004

Graft-versus-host disease is associated with a lower relapse incidence after hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.

To determine the graft-versus-leukemia effect after hematopoietic stem cell transplantation (HSCT), we studied 199 patients with acute lymphoblastic leukemia who underwent transplantation at Huddinge University Hospital between 1981 and 2001. Seventy-four patients were in first complete remission (CR1), and 125 were in later stages of the disease. Most patients had an HLA-identical sibling donor. Conditioning consisted mainly of total body irradiation and cyclophosphamide, and graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. Acute GVHD developed in 143 patients and chronic GVHD in 67. The 5-year probability of relapse and relapse-free survival (RFS) were 32% and 49%, respectively, in patients in CR1, as compared with 53% and 33% in those with more advanced disease. In the multivariate risk factor analysis of relapse, we found that the absence of chronic GVHD (P<.001), absence of herpes simplex virus infection after HSCT (P=.003), combination prophylaxis with methotrexate and cyclosporine (P=.01), and >6 weeks from the diagnosis to CR (P=.025) were independent risk factors for relapse after HSCT. Factors associated with a better relapse-free survival were chronic GVHD (P<.001), ABO blood group mismatch (P=.006), younger patient age (P=.01), and an HLA-matched donor (P=.01). The association between herpes simplex virus infection and a low frequency of relapse is a new observation and may indicate that viral antigens play a role in the induction of an antileukemic effect.

Adolescent↗

PubMed2006

KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy.

Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval, .043-0.85; P = .004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P = .004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P = .04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P = .95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants.

Disease-Free Survival↗

PubMed2005

Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse.

Discontinuation of benzodiazepine (BZD) treatment for insomnia can be a difficult task. Cognitive-behavior therapy (CBT) for insomnia, combined with a supervised medication taper, can facilitate withdrawal but there is limited evidence on long-term outcome after discontinuation. The objective of this study was to examine medication-free survival time and predictors of relapse (i.e., resumed BZD hypnotics) over a 2-year period in 47 older adults (mean age 62.1 years) with persistent insomnia and prolonged BZD use (average duration of 18.9 years), who had successfully discontinued BZD following CBT for insomnia, a supervised medication taper program, or a combined approach. The Kaplan-Meier product-limit method was used to estimate survival time, defined as time between end-of-treatment and relapse or end of follow-up. By the end of the 24-month follow-up, 42.6% of the samples had resumed BZD use. Participants in the Combined (33.3%) and Taper (30.8%) groups relapsed significantly less than their counterparts from the CBT group (69.2%). Survival rates at 3 months were 61.5% (CBT), 100% (Taper), and 80.9% (Combined). At 12 months, they were 38.5%, 83.3%, and 70.8%, respectively; and, at 24 months, they were 28.9%, 64.8% and 64.9%, respectively. Mean survival time was significantly longer for both the Taper (18.6 months, SE = 2.1) and Combined groups (12.6 months, SE = 1.4), relative to the CBT group (8.5 months, SE = 1.8). Significant predictors of relapse included treatment condition, end of treatment insomnia severity, and psychological distress. In conclusion, there is a substantial relapse rate following BZD discontinuation among prolonged users. CBT booster sessions might enhance compliance with CBT and prove useful in preventing relapse.

Aged↗

PubMed2004

Inhaled dexamethasone differentially attenuates disease relapse and established allergic asthma in mice.

Inhaled glucocorticoids are effective in patients with chronic allergic asthma. We examined the effects of inhaled glucocorticoids on relapse (allergen challenge after disease remission) and established/overt allergic asthma (repeated allergen challenge in weekly intervals) in mice to establish a reference standard for novel treatments. BALB/c mice were treated before relapse or during overt disease with 1 h of nebulized PBS or 10 mg% dexamethasone twice daily for 5 days. Dexamethasone eliminated airway hyperresponsiveness before relapse and during overt disease. They more efficiently reduced airway inflammation, mucus production, and OVA-specific IgG1 and IgE during relapse compared to overt disease. However, during overt disease, parenchymal inflammatory infiltrates were more effectively eliminated compared to relapse, suggesting that activated infiltrating leukocytes have increased sensitivity to steroids. These data demonstrate that inhaled corticosteroids attenuate relapse and overt disease differentially and suggest that both airway and parenchymal inflammation need to be evaluated for treatment efficacy.

Administration, Inhalation↗

PubMed2006

Second-generation antidepressant discontinuation and depressive relapse in adult patients with bipolar depression: results of a retrospective database analysis.

BACKGROUND: To date, few postmarketing studies have addressed whether long-term prophylactic treatment with second-generation antidepressants (ADs) delays depressive episodes in patients with bipolar disorder. OBJECTIVE: The aim of this study was to compare the risk of depressive relapse between patients with bipolar disorder who took second-generation ADs>-6 months after depressive remission with those who discontinued AD use early. METHODS: Using a large US managed-care claims database, continuously enrolled bipolar subjects who took second-generation ADs after a depressive remission were identified between January 1, 1998, and December 31, 2002. Duration of AD and concurrent mood stabilizer use were based on coded diagnoses and pharmacy records. A Cox proportional hazards model was developed to predict time from depressive remission to next depressive relapse with continuous AD use, categorized as either >or=6 months or <6 months. Propensity scoring with greedy matching was used to help balance the observed background covariates and baseline disease severity between groups. RESULTS: Five hundred eighty-nine subjects met the inclusion criteria. A Kaplan-Meer estimate found that the median depressive relapse times for the continuous (ie, >or=6 months) and early discontinuation (ie, <6 months) AD treatment groups were 16.5 and 6.8 months, respectively (P<0.05). The Cox proportional hazards model with propensity score matching identified a significantly lower risk of depressive relapse over a 2-year period among those who continued AD treatment>or=6 months after remission, compared with those who discontinued treatment within 6 months (hazard ratio, 0.61 [95% CI, 0.42-0.88]; continuous vs early discontinuation, P<0.01). CONCLUSIONS: Continuous second-generation AD therapy for >or=6 months after depressive remission was associated with a lower risk of depressive relapse over a 2-year period in patients with bipolar depression. Given concerns regarding the risk of AD users with bipolar disorder switching to mania, an optimal prophylactic treatment after depressive remission should balance the risks between manic switching and depressive relapse.

Adolescent↗

PubMed2005

Relapse in the addictive behaviors: integration and future directions.

This paper identifies the major consistencies in substantive and methodological findings across the review papers in this special issue on relapse in the addictive behaviors. The papers were consistent in suggesting that there have been major methodological advances which have helped to move the field forward. Furthermore, the papers show the need for taking a biopsychosocial approach to the study of relapse and the major difficulty across addictive behaviors in creating an acceptable operational definition of relapse. Suggestions for future research directions that follow from the papers include deriving and evaluating relapse definitions, systematically developing and testing models and theories of relapse, and understanding and narrowing the relapse research-clinical practice gap.

Alcoholism↗

PubMed2005

Prediction of relapse to frequent heroin use and the role of methadone prescription: an analysis of the Amsterdam Cohort Study among drug users.

The risk of relapse into frequent heroin use was studied among 732 participants of the Amsterdam Cohort Study (ACS) on HIV/AIDS among drug users, who experienced an episode of abstinence from or occasional use of heroin. Participants of the ACS were recruited primarily from easy access ("low-threshold") methadone programs. The duration of abstinence/occasional use and relative risks (RR) of relapse were estimated by analyzing 1577 episodes by means of survival analysis using characteristics of patients and methadone treatment as covariates. The majority of episodes (85.8%) were followed by relapse within 5 years. Less education, intense use of heroin prior to the episode of abstinence or well-controlled use, occasional use of heroin and intense use of cocaine during the episode, and having a drug-using partner or having no partner were significantly associated with a higher risk of relapse. Among frequent attendees of a "low-threshold" methadone program, relapse was associated with the daily dose of methadone: RR for dosages <40 and 40-60 mg, compared with doses of >100mg, were 1.45 (P<0.01) and 1.59 (P<0.01), respectively. No beneficial influence was revealed of methadone dosage or program attendance in itself on the risk of relapse into cocaine. High doses of methadone in a harm-reduction setting extend the duration of an episode of no or occasional use of heroin. Other factors, such as no occasional use of heroin during the episode, no use of cocaine, and having a non-using partner, seem to be equally important.

Adult↗

PubMed2006

Development and validation of the Stimulant Relapse Risk Scale for drug abusers in Japan.

OBJECTIVE: To develop and validate a multidimensional measure of relapse risk for stimulants in Japanese drug abusers. METHODS: A Stimulant Relapse Risk Scale (SRRS) was developed based on the Marijuana Craving Questionnaire and a discussion among three psychiatrists. We created 48 items after confirming the items including a variety of relapse risk, such as craving (expectancy, compulsivity, etc.) and emotionality problems. One hundred inpatients and outpatients with a history of stimulant abuse (71 males and 29 females) were recruited with informed consent, and were administered the SRRS. The Visual Analogue Scale for drug craving (VAS), Addiction Severity Index for Japanese (ASI-J), and data on relapse within 3 and 6 months after the rating were used for the validation. RESULTS: Exploratory factor analysis highlighted five factors: anxiety and intention to use drug (AI), emotionality problems (EP), compulsivity for drug use (CD), positive expectancies and lack of control over drug (PL), and lack of negative expectancy for drug use (NE). These accounted for 48.3% of the total variance. Thirty of the 43 items were classified into the five subscales. Cronbach's alpha coefficient for each subscale ranged from .55 to .82, and was .86 for the total SRRS, indicating their adequate internal consistency. AI, CD, PL, and total SRRS were significantly correlated with the drug-use composite score of the ASI-J, supporting their concurrent validity. AI, PL, NE, and total SRRS were significantly correlated with relapse, implying their predictive validity. CONCLUSIONS: The SRRS has multidimensional psychometric properties useful for assessing the various aspects of stimulant relapse risk.

Adult↗

PubMed2004

Efficacy of early retreatment with interferon beta for relapse in patients with genotype Ib chronic hepatitis C.

BACKGROUND: Interferon (IFN) retreatment for hepatitis C virus (HCV) relapsers has been effective under some conditions. We conducted a randomized, controlled trial of IFN beta retreatment for HCV relapsers after IFN alpha. PATIENTS AND METHODS: We gave IFN beta 6MIU therapy to 43 patients who had relapse of HCV after the 24 weeks IFN alpha monotherapy. The 43 patients were randomly assigned to two groups: Group A started retreatment within 4 weeks after relapse; and Group B started retreatment 24 weeks or more after relapse. RESULTS: Nine patients showed sustained virological response (SR) to the retreatment. All of these patients were in a low viral load subgroup. The SR rate in Group A (8/22, 36%) was significantly higher than in Group B (1/21, 5%) (P=0.0128). Among patients with lower viral load, the SR rate in Group A (8/10, 80%) was also significantly higher than in Group B (1/8, 13%) (P=0.0076). CONCLUSION: The retreatment with IFN beta is effective for patients with HCV low viral load, and the sooner after the relapse the retreatment is started, the better the clinical results will be.

Journal Article↗

PubMed2006

Treatment of relapsers after combination therapy for chronic hepatitis C.

Sustained virologic response rates are significantly higher in patients who have relapsed after a previous course of therapy compared with patients who did not respond. A meta-analysis of combination therapy in patients who failed IFN monotherapy reported SVR rates of 52% in relapsers to prior therapy and 16% in nonresponders. Similarly, relapsers after combination standard IFN and RBV therapy have higher SVR rates than combination of therapy nonresponders when treated with pegylated interferon and ribavirin. For this reason, patients who relapse after a previous course of therapy should be considered potential candidates for retreatment. Factors that have been associated with SVR in these patients include genotype non-I, low viral loads, and lesser degrees of fibrosis. The course of treatment in all patients who have relapsed after prior therapy should be reviewed to identify possible reasons for failure to achieve an SVR. In particular, optimal dosing of PEG IFN and RBV and the occurrence and timing of treatment dose reductions during prior therapy should be reviewed. The reasons for dose reduction should be addressed before initiating another course of therapy in an effort to optimize the chance for a SVR. Patients who had dose reduction for depression, anemia, or neutropenia, should be considered for antidepressants, erythropoietin, or, if neutropenia is severe, granulocyte colony stimulating factor therapy, respectively, during retreatment. Prolongation of therapy beyond 48 weeks in patients with relapse after a standard course of PEG IFN and RBV may offer a chance of SVR. Novel agents currently in development, including protease and polymerase inhibitors, may prove to be therapeutic options for these patients in the future.

Journal Article↗

PubMed2006

Hypothalamic-pituitary-adrenocortical responses to psychological stress and risk for smoking relapse.

Stress is a commonly reported precipitant of relapse to substance use. There is a growing recognition of the need to understand psychobiological alterations in the stress response among chronic drug users, and to determine how they may precipitate relapse. This paper focuses on the hypothalamic-pituitary-adrenocortical (HPA) response to stress among dependent smokers. Nicotine acutely activates the HPA axis, and increased HPA activity has been linked to attenuated CNS nicotinic receptor sensitivity. We will review a series of studies demonstrating that steep decline in cortisol concentrations during early abstinence and hyporesponsiveness to stress predict shorter time to relapse. Our studies show that hormonal associations with smoking relapse tend to be more consistent in men, while intensity of withdrawal symptoms tend to be consistent predictors of smoking relapse in women. We propose that perturbed HPA activity during early smoking abstinence exacerbate withdrawal symptoms and may contribute to the rapid relapse observed in the majority of smokers. Our results also reinforce the need for gender-specific investigation of mechanistic and interventional strategies to combat nicotine addiction.

Adult↗

PubMed2005

Increased levels of bioactive IL-16 correlate with disease activity during relapsing experimental autoimmune encephalomyelitis (EAE).

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T-cell mediated disease, which resembles immunopathology of multiple sclerosis (MS). Interleukin (IL)-16 is a CD4+ cell-specific chemoattractant cytokine. In CD4+ T cells, production of bioactive IL-16 from constitutive pro-IL-16 requires cleavage by active caspase-3. We reported reversal of established relapsing disease by IL-16 neutralization. To better understand role(s) of IL-16 in regulation of relapsing EAE, we comparatively analyzed levels of IL-16, active caspase-3 and CD4 in mice with severe relapsing-remitting [(B6xSJL) F1], and low-relapsing (B6), disease. Elevated levels of IL-16 along with an increase in active-caspase-3 and CD4 levels correlated with stages of clinically active disease in both strains. CNS levels of bioactive IL-16 were notably higher in F1 compared to B6 mice at all stages, being most prominent during relapse. Similar patterns of regulation for IL-16 and active caspase-3 were observed in peripheral lymphoid organs, and in T cells isolated from lymph nodes following T-cell activation in vitro. IL-16 was co-immunoprecipitated with CD4 from CNS of relapsing mice. Our data suggest that caspase-3 mediated production of IL-16 by infiltrating CD4+ T cells, contributes to ongoing neuroinflammation by chemoattraction of additional waves of CD4+ T cells.

Amino Acid Sequence↗