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PubMed1995

Prodromal symptoms and relapse prevention in schizophrenia.

The value of monitoring for prodromal symptoms in patients with schizophrenia has been questioned by some investigators who point out that their positive predictive value, sensitivity, and specificity can be low in relation to relapse. This article focuses on methodological and conceptual issues which should be considered in evaluating the usefulness of prodromal symptoms and behaviors as part of the relapse process. The article presents the following conclusions: Many relapses are preceded by the appearance of prodromal symptoms and behaviors which may last from a few days to a few weeks or more. The presence of prodromal symptoms often does not predict impending relapse since the probability of progression to relapse depends on the complex interaction of many personal and environmental factors including the availability of prompt and effective psychiatric intervention. Finally, studies have shown that monitoring for prodromal symptoms and early intervention when they emerge is effective in reducing the likelihood of relapse in individuals with schizophrenia.

Humans↗

PubMed1997

Patient attributes and expressed emotion as risk factors for psychotic relapse.

In the context of a prospective, controlled treatment study, contrasting family interventions with individual treatment, the role of expressed emotion (EE) as a predictor of relapse was examined in patients with recent-onset schizophrenia and related disorders (n = 97). EE was compared with 13 predictor variables. The variables, taken from EE and family intervention studies, related to demography, premorbid functioning, present and past illness history, and comorbid substance abuse. Psychotic relapse was operationalized with a conservatively measured relapse criterion, composed of monthly ratings based on the Brief Psychiatric Rating Scale and on clinical judgment during the 12 months of outpatient treatment. Of the 14 predictor variables entered in stepwise survival analyses, 6 variables had probable predictive power on the conservative relapse criterion. These variables were entered in a Cox regression model. EE turned out to be the major predictor of relapse in the overall sample (hazard ratio [HR] 4.90; confidence interval [CI] 1.05-22.92). This finding remained when only patients with a first psychotic episode (p = 0.02) and patients in the individual treatment condition (p = 0.001) were examined. Cannabis abuse was the major predictor of relapse in patients with high-EE families (HR 4.27; CI 1.12-16.29).

Adolescent↗

PubMed1983

Survival, prognostic factors, and relapse patterns in uterine cervical carcinoma.

Between 1965 and 1979, 295 evaluable patients were treated with radiotherapy and/or surgery for invasive cervical carcinoma at the Stanford University Medical Center. The records of these patients were analyzed retrospectively with regard to survival, possible prognostic factors of freedom-from-relapse, and relapse patterns. Survival for the entire population at 5 years was 67%, with a median follow-up of 5 years. Five-year freedom-from-relapse (FFR) rates for stages I-IV were 88%, 61%, 33%, and 11%, respectively. Eighty-eight percent of all relapses occurred within 5 years. Several possible prognostic factors of FFR--including stage, histology, tumor differentiation, lymphangiogram status, treatment modality, age, presence of cervical stump, and initial serum hemoglobin value--were evaluated with a multivariate analysis. Stage was the best predictor of FFR, and lymphangiogram (LAG) status was the next most important covariate: 13 of 19 patients who showed involvement of paraaortic nodes on LAG relapsed within 1 year. There was no difference in survival or FFR between adenocarcinoma or squamous cell histologies. FFR in stage IB patients was independent of treatment modality; i.e., radiotherapy alone, surgery alone, or combined therapy. Initial serum hemoglobin (less than 12 vs. greater than 12) was not predictive of FFR or survival. Stage for stage, patients over 57 years of age tended to have better FFR than younger patients. The majority of relapses occurred centrally or at the pelvic sidewalls (58%), and future attempts to improve local control rates will rely more heavily on the individualized use of interstitial template applicators.

Adenocarcinoma↗

PubMed1990

An unusual extramedullary relapse of acute nonlymphocytic leukemia after allogeneic bone marrow transplantation.

Recurrent leukemia following allogeneic bone marrow transplantation (BMT) for acute nonlymphocytic leukemia (ANLL) continues to be a cause of morbidity and mortality. Most relapses occur within the first 6-12 months, although disease-free survival curves do not begin to plateau until 24 months posttransplant. The majority of relapses occur in the bone marrow. Extramedullary relapses usually occur in "sequestered sites," i.e., the testis and central nervous system. Although the true incidence of extramedullary relapse in "nonsequestered" sites after allogeneic BMT for ANLL is unknown, it appears that this type of relapse is distinctly unusual. The authors present a case of an unusual extramedullary relapse of ANLL in the breast at day +613 after allogeneic BMT for ANLL. In addition, we briefly review the English BMT literature and discuss the differential diagnosis of breast masses in women who survive allogeneic BMT for ANLL.

Adult↗

PubMed1999

Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons.

OBJECTIVE: To determine the rate of tuberculosis relapse among HIV-seropositive and -seronegative persons treated for active tuberculosis with short-course (6-month) therapy. DESIGN: Consecutive cohort study. SETTING: City of Baltimore tuberculosis clinic. PATIENTS: Tuberculosis patients treated between 1 January 1993 and 31 December 1996. INTERVENTION: Patients received 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin. MAIN OUTCOME MEASURE: Passive follow-up for tuberculosis relapse was performed through September 30, 1998. RESULTS: There were 423 cases of tuberculosis during the study period; 280 patients completed a 6-month course of therapy. Therapy was directly-observed for 94% of patients. Of those who completed therapy, 47 (17%) were HIV-seropositive, 127 (45%) were HIV-seronegative, and 106 (38%) had unknown HIV status. HIV-infected patients required more time to complete therapy (median 225 versus 205 days; P = 0.04) but converted sputum culture to negative within the same time period (median 77 versus 72 days; P = 0.43) as HIV-seronegative or unknown patients. Relapse occurred in three out of 47 (6.4%) HIV-infected patients compared to seven out of 127 (5.5%) HIV-seronegative patients (P = 1.0). Relapse rates also did not differ when HIV-seropositive patients were compared with HIV-seronegative and patients with unknown HIV status (6.4% versus 3.0%; P = 0.38). Of the 10 patients with tuberculosis relapse, restriction fragment length polymorphism data were available for five; all five relapse isolates matched the initial isolate. CONCLUSIONS: These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.

AIDS-Related Opportunistic Infections↗

PubMed1996

Gender differences in the relapse experiences of cocaine patients.

This study investigated potential gender differences in the onset, course, and termination of cocaine relapse episodes. The subjects were 98 cocaine dependent men and women who were participating in several treatment outcome studies. The Cocaine Relapse Interview was used to obtain data on specific relapse episodes that had occurred in a 6-month period before the interview. The analyses indicted that women reported more unpleasant affect and interpersonal problems and fewer positive experiences before relapse than men, and their relapses were more likely to have an impulsive quality. Women reported more help-seeking after initial use, whereas men reported stronger appetitive reactions and more self-justification. There were no gender differences in factors associated with terminating the relapse episodes. Clinical implications and limitations of the research are discussed.

Adolescent↗

PubMed2001

Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance.

INTRODUCTION: In a large number of patients on HAART who achieved plasma HIV RNA levels below the limit of detection (50 copies/ml), transient relapses of HIV RNA levels ("blips") are observed. OBJECTIVE: To determine whether relapses of plasma HIV RNA during HAART are associated with development of drug resistance. METHODS: Plasma samples from 15 patients with a transient viral load relapse during HAART were studied. All regimens contained lamivudine (3TC). We used an ultrasensitive sequence approach to analyze the presence of drug resistance mutations during the relapse. RESULTS: The median plasma HIV RNA load of the relapse was 76 copies/ml (range 50-1239). In 11 of 15 cases, a genotype of HIV could be obtained. Mutations in the RT and protease gene conferring resistance to one or more drugs were observed in 8 of 11 patients, 6 of whom had the M184V substitution. During a median follow-up of 27 months after the relapse, plasma HIV RNA levels remained undetectable in 13 of 15 patients. CONCLUSIONS: Plasma HIV RNA blips during HAART can be associated with selection of drug-resistant HIV. This indicates that viral replication may occur during HAART, probably caused by a temporary decrease in active drug concentrations. A blip containing only wild-type virus is not necessarily caused by viral replication. In this situation the raise of HIV RNA could also originate from release of wild-type viruses, caused by activation of the latent virus reservoir. Independent of the mechanism, blips did not preclude successful inhibition of viral replication during 2-year follow-up in the majority of these cases.

Anti-HIV Agents↗

PubMed2003

Fecal alpha 1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn's disease of the distal ileum.

BACKGROUND: Crohn's disease (CD) shows a chronic relapsing course but no marker of relapse is currently available. However, fecal alpha 1-antitrypsin (alpha 1-AT) clearance (alpha 1-ATCl) is an indicator of protein loss and increases during active inflammation. We assessed the usefulness of fecal alpha 1-ATCl in predicting clinical relapse in patients with inactive ileal CD. DESIGN: In a prospective longitudinal study, 26 patients with inactive ileal CD (Crohn's disease activity index (CDAI) < 150) (18 males, mean age 43 +/- 10, range 23-58) were enrolled. Fecal alpha 1-ATCl and concentration, daily stool weight and serum alpha 1-AT were measured at baseline (visit 1), after 1 week (visit 2) and 3 weeks (visit 3) in 24/26 patients (two drop-outs) (short-term study). In six of these 26 patients, fecal alpha 1-ATCl was also measured every 3 months for 1 year (long-term study). All patients were clinically assessed every 3 months for 1 year and every 6 months for 2 years. Ten healthy volunteers were tested as controls. METHODS: Serum and fecal alpha 1-AT concentration was quantified by radial immunodiffusion. RESULTS: The median fecal alpha 1-ATCl value at baseline was higher in inactive patients undergoing clinical relapse (CDAI > 200) in the next 6 months than in those remaining in remission at 6 months (P = 0.03). Fecal alpha 1-ATCl showed a 75% sensitivity, 85% specificity, 50% positive predictive value and 94% negative predictive value in predicting CD relapse in the next 6 months. In the long-term follow-up, fecal alpha 1-ATCl values increased at 12 months compared with both baseline and 6 month values (P = 0.005; P = 0.009). Fecal alpha 1-ATCl was higher in patients with raised C-reactive protein (P = 0.039). CONCLUSIONS: Results from our study suggest that fecal alpha 1-ATCl is an indicator of clinical relapse in patients with CD of the distal ileum under regular surveillance.

Adult↗

PubMedDate not supplied

Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia.

PURPOSE: We evaluated the influence of three different dosages of methotrexate (MTX) during consolidation on the incidence of testicular relapse in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: One thousand one hundred forty-four boys with newly diagnosed ALL, enrolled in three consecutive trials of the Berlin-Frankfurt-Münster group (ALL-BFM 81, 83, 86), were retrospectively evaluated for the influence of MTX on testicular relapse-free interval. The basic treatment design was similar in all trials. No intravenous MTX was used in trial ALL-BFM 81 in the group who received cranial irradiation (CRT) except for a part of standard risk patients. Four courses of intermediate dose MTX (IDM) (0.5 g/m2) were introduced for all patients in trial ALL-BFM 83 (IDM group), which were replaced by high dose MTX (HDM) (5 g/m2) in trial ALL-BFM 86 (HDM group). The media observation time was > 9 years. RESULTS: The cumulative incidence of isolated testicular relapses was significantly higher in the CRT group as compared to the IDM and HDM groups (6.7% versus 2.5% and 2.3%, p = 0.02 and 0.01). HDM decreased neither the incidence nor the rate of isolated testicular relapses any further. Event-free survival (EFS) for boys was similar between trial ALL-BFM 81 and 86 (64% versus 69%, p = 0.35), but differed significantly between trials ALL-BFM 83 and 86 (61% versus 69%, p = 0.0078). CONCLUSION: The introduction of IDM reduced the incidence of isolated testicular relapses significantly by a factor two, but had no significant influence on overall survival. HDM did not result in a more effective prevention of testicular relapses, but resulted in better systemic control and hence better survival than IDM.

Antimetabolites, Antineoplastic↗

PubMed2001

Seven keys to relapse prevention in schizophrenia.

Relapse prevention is a primary goal in the treatment of schizophrenia. Relapse can cause significant personal distress, interfere with rehabilitation efforts, and result in psychiatric hospitalization. The emergence of psychotic symptoms and disruptive behaviors can also lead to arrest and incarceration, particularly among patients who are not engaged in treatment. This article focuses on the process of relapse in schizophrenia and theoretical foundations of relapse prevention. The Program for Relapse Prevention is presented, along with the results of a recently completed controlled prospective evaluation. Based upon this study and the current literature, the author presents a series of seven clinical strategies for optimal relapse prevention.

Journal Article↗

PubMed2006

Chemokine IL-8 and chemokine receptor CXCR3 and CXCR4 gene expression in childhood acute lymphoblastic leukemia at first relapse.

In this study, we examined the gene expression of interleukin (IL)-8, CXCR3, and CXCR4 in leukemic cells from 100 children with relapsed B-cell progenitors (BCP) acute lymphoblastic leukemia (ALL), using quantitative real-time polymerase chain reaction (RT-PCR). IL-8, CXCR3, and CXCR4 were expressed in almost all bone marrow (BM) samples. The CXCR4 expression significantly correlated with known prognostic factors at relapse: time point and site of relapse. Patients who had a combined BM relapse (n=21) had lower IL-8 and CXCR4 expression than those who had an isolated BM relapse (n=79). The CXCR3 expression was higher in female patients (n=39) than in male patients (n=61). However, this did not reach prognostic relevance in relapsed ALL.

Bone Marrow↗

PubMed1997

Relationships between social support, social coping and life events in the relapse of schizophrenic patients.

The vulnerability-stress model for schizophrenia posits that relapses are at least partly determined by interacting triggering and protecting psychosocial factors. This study examined social support and general coping style in 42 consecutively admitted DSM:III schizophrenic patients, who were followed prospectively for up to four years. In a second part of the study, a subgroup of the patients were interviewed using the Life Event and Difficulty Schedule 9 months after discharge or at relapse. Patients contented with low social integration had a higher relapse rate over four years than patients lacking of social provisions, but wanting more. We found an excess of life events three weeks before relapse compared to events reported in the non-relapsing group. Suggesting a buffering effect of social factors, time between life event and relapse was significantly extended among patients with a high availability of attachment and a coping strategy characterised of active support seeking.

Adaptation, Psychological↗

PubMed1992

Smoking habits in relapsed subjects from a smoking cessation trial after one year.

Reports of smoking cessation studies often claim that many relapsed subjects reduce their smoking. We investigated the smoking habits of relapsers 1 year after quitting in a smoking cessation trial using nicotine or placebo patches. All 289 participants in that study were summoned to a 1-year follow-up visit--148 (57%) of 259 relapsers attended, as did all 30 sustained abstainers. Fewer than 1% of the subjects had quit spontaneously after the primary relapse. Daily cigarette consumption, standard nicotine yield per cigarette, saliva cotinine concentration, expired carbon monoxide level and two nicotine dependency scales were assessed at entry and at the 1-year follow-up. In five of these six smoking-related characteristics, there was a small but significant mean reduction of 7%-27%. A significant weight gain of 0.5 +/- 2.9 kg (mean +/- SD) was recorded in the relapsers compared with 4.8 +/- 4.2 kg for abstainers (p less than 0.001). It is concluded that smoking habits in relapsers are relatively unchanged, and thus the most important outcome measure in smoking cessation trials is abstinent subjects.

Administration, Cutaneous↗

PubMed1993

Minimal residual disease after allogeneic bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: correlations with acute graft-versus-host disease and relapse.

We have studied 61 patients who underwent allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) in first chronic phase. Minimal residual disease was detected by the amplification of the leukaemia-specific BCR-ABL fusion mRNA with the polymerase chain reaction (PCR) using a highly sensitive nested primer strategy. As a general pattern, patients often had detectable BCR-ABL (PCR positive) for up to 6 or 9 months post BMT after which time BCR-ABL became undetectable (PCR negative). The conversion from PCR positive to PCR negative was not associated with the time at which cyclosporin A treatment was stopped. Six patients (10%) have relapsed during the period of this study, two within 1 year and four more than 1 year after transplant. The relationship between PCR positivity more than 1 year post transplant and relapse was significant (P = 0.036) but 15 patients who were PCR positive beyond 1 year remain in complete clinical and cytogenetic remission. Thus late positivity identifies a group of patients at increased risk of relapse but is of little predictive value for individual patients. Of the four late relapses, two had been persistently PCR positive and two were initially PCR positive, converted to negative and subsequently to positive again. Although all relapses were preceded by PCR positivity, relapse may occur only 12 months after a PCR negative result. The proportion of patients PCR negative at 3/4 months after BMT was found to increase significantly with the severity of acute GVHD (P = 0.002) but no relationship was found between acute GVHD and subsequent PCR results. There was no clear association between severity of chronic GVHD and PCR result.

Acute Disease↗

PubMed2005

Outcome after first relapse in childhood acute lymphoblastic leukaemia - lessons from the United Kingdom R2 trial.

A retrospective analysis of children with first relapse of acute lymphoblastic leukaemia (ALL), treated on the UKALL R2 protocol at four different hospitals, between June 1995 and December 2002 was performed. Of the 150 children 139 (93%) achieved a second complete remission. The overall survival (OS) and event-free survival (EFS) for the whole group was 56% and 47% respectively. The duration of first complete remission and immunophenotype, but not sites of relapse, were predictive for survival. Using the Berlin-Frankfürt-Münster risk stratification for relapsed ALL, the OS and EFS for standard, intermediate (IR) and high risk (HR) groups were 92% and 92%, 64% and 51%, and 14% and 15%, respectively; P < 0.0001 for both OS and EFS. In the IR group, those with a very early isolated central nervous system relapse also had a significantly worse outcome (P = 0.0001). Given the poor outcome of a second relapse, clear strategies are required to identify those in the IR group who will most benefit from stem cell transplantation (SCT). A higher proportion (16%) of induction failures in the HR group suggest the need for novel agents during this phase of treatment, but SCT was associated with a lower relapse rate and better outcome than those treated with chemotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Loss of natural killer activity as an indicator of relapse in acute leukaemia.

A role for naturally occurring cytotoxic cells in immunosurveillance against malignancy has been presumed in several studies. The natural killer activity (NKA) of peripheral blood mononuclear cells was therefore measured at regular intervals in patients with acute leukaemia and expressed specific cytotoxicity. Sixty controls had a median NKA of 33.6% (range 15.4-71). Seventy-three patients with acute lymphoblastic leukaemia (ALL) and acute non-lymphoblastic leukaemia (ANLL) with untreated or relapsed disease had a median activity of 2.4% (range 0-13.4) (P less than 0.001), while 57 patients who had achieved complete remission had a median activity of 22.7% (range 9.5-64.4). In 15 patients, reductions of NKA were seen prior to 16 episodes of relapse. In ten of these (nine with ANLL and one with ALL), 11 relapses were preceded within 10 weeks by drops in NKA to less than 30% of remission levels. The median NKA of the group prior to the drop in activity was 25.5% and the median first low value was 6.0%. Five patients who relapsed after allogeneic bone marrow transplantation had significant, sustained drops in NKA, 5-9 weeks earlier. The median NKA prior to the drop was 25.6% and the median first low value was 8.0%. We therefore conclude that there was a marked reduction in NKA in patients with active acute leukaemia when compared with healthy blood donors and that this activity substantially improved in complete remission. All patients who relapsed had significantly reduced NKA which in some, significantly preceded the time of relapse. These data suggest that the regular assessment of NKA in patients with acute leukaemia may be a useful diagnostic tool.

Adolescent↗

PubMed1993

Prodromal symptoms of relapse in schizophrenic outpatients: retrospective and prospective study.

Of 61 schizophrenic outpatients in remission, 33 who had relapses within the past 20 months were retrospectively examined for prodromal symptoms of relapse. Four weeks prior to the relapse, 63.6% manifested 4 prodromal symptoms, which were somatic concern, feeling of tiredness, anxiety and depressive mood. Contrarily, with the GAS evaluation, no significant deterioration was recognized until one week before the relapse. Subsequently, a prospective observation of symptoms in 43 patients was conducted for 7 months to determine whether therapeutic intervention at the time of the manifestation of prodromal symptoms could be effective in the prevention of relapses and the improvement of outcome of relapses, and to consider the therapeutic use of this method.

Adult↗

PubMed1996

Studies on relapse, course and outcome of schizophrenia in Japan.

Studies of the long-term outcome of schizophrenia in Japan are reviewed. In nine studies over a 10 year period, recent reports on three patient cohorts show that the liability to relapse is the major difficulty in the treatment and care of schizophrenia. Other research on relapse-related problems in schizophrenia are also reviewed. Relapses appear mainly in the first decade after onset of the condition; in stressful situations related to a family or larger social context; and on cessation of psychotropic drugs. Relapse liability develops during the course of schizophrenia, but the characteristics of the relapses vary with both the duration and the episodic nature of the schizophrenic condition. Two types of unique treatments that are specifically aimed at coping with relapses, and which were developed in Japan, are described: 'Seikatsu-Rinsho' (clinical guidance to the way of life) and 'Soegi-Ryoho' (splint therapy).

Adaptation, Psychological↗