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Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group.

PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.

Antibiotics, Antineoplastic↗

Steroid-resistant, cyclosporine-responsive, relapsing nephrotic syndrome.

Eighteen children with steroid-resistant nephrotic syndrome received cyclosporine A (CsA), including 7 patients with minimal change disease, 4 with focal segmental glomerulosclerosis and 7 with mesangial hypercellurarity. Doses were adjusted to maintain whole blood trough levels at 80-200 ng/ml and ranged from 5 to 10 mg/kg (mean 7 mg/kg). Fourteen patients responded after 2 months of therapy with either a complete or partial remission, and received a total of 12 months of CsA with low-dose corticosteroids. Remission rates were similar among the three histological types, although complete remissions occurred more commonly in minimal change disease, while the other two histological types tended to have partial responses. Serum creatinine values ranged from 0.3 to 1.2 mg/dl at the start of treatment and were stable in 17 of 18 patients during CsA therapy. CsA was discontinued after 12 months in 11 responders. Relapses were a significant problem. Nine patients had 16 relapses, all occurring within 6 months after discontinuing CsA; 13 of 16 relapses responded to CsA and corticosteroids. Five children had multiple relapses. Three patients who initially responded to treatment had CsA-resistant relapses. There were no differences among the histological types with respect to the occurrence of relapses or response to CsA after relapsing. Four patients developed chronic renal failure, including 2 of 4 who failed initial therapy and 2 of 3 who developed CsA-resistant relapses. In conclusion, initial therapy with CsA was effective in resolving nephrotic syndrome in steroid-resistant patients. However, CsA dependency, frequent relapses and the development of chronic renal failure presented significant problems.

Adolescent↗

Compliance and laboratory data predict relapse rate of Pneumocystis carinii pneumonia during prophylaxis with aerosol pentamidine.

We evaluated 43 AIDS patients on prophylaxis with aerosol pentamidine (60 mg biweekly) after Pneumocystis carinii pneumonia (PCP). The effects of patients' inhalation compliance and of laboratory data during the initial PCP on subsequent PCP relapses were assessed. After a median of 8 months (range, 2-21.5 months) on pentamidine prophylaxis, 13 patients suffered a PCP relapse. Six of them had missed at least one inhalation within the last month before the relapse. Two of these six relapses were fatal. The relapse occurrence was significantly associated with the percentage of missed inhalations. Additional significant associations were found between relapses, low levels of T4 lymphocytes, and elevated serum lactate dehydrogenase during the initial PCP episode (29 patients). Mean levels of T4 lymphocytes were 27/mm3 and 47/mm3 in patients with and without subsequent relapses, mean levels of lactate dehydrogenase were 692 U/L and 605 U/L, respectively. Multivariate Cox regression did not reveal further differences between patients with and without relapses. The increased relapse risk associated with poor inhalation compliance stresses the need for appropriate guidance and motivation of the patients.

Acquired Immunodeficiency Syndrome↗

High incidence of relapses in thrombotic thrombocytopenic purpura. Clinical study of 38 patients.

Described in this study are 38 patients who received treatment for thrombotic thrombocytopenic purpura in 15 hospitals in Israel and the New York City area since 1977, when plasma therapy was introduced. Thirty-seven patients received plasma therapy and 30 survived. In 12 patients (37 percent of survivors), relapsing thrombotic thrombocytopenic purpura developed, manifested by thrombocytopenia and microangiopathic hemolytic anemia, and less frequently by neurological or renal abnormalities. Six patients had a second relapse, and two had five relapses. To assess the severity of the disease, a scoring system was designed based on the four major manifestations of thrombotic thrombocytopenic purpura listed above. The patients who died had a significantly higher score than those who survived. The initial episodes and the relapses of patients with relapsing thrombotic thrombocytopenic purpura were milder than those in patients who only had a single episode and survived. Two relapses, however, were fatal, demonstrating that relapsing thrombotic thrombocytopenic purpura is not a benign disorder. Infections, pregnancy and surgery were frequently associated with the initial episodes and the relapses. Hence, patients who recover from thrombotic thrombocytopenic purpura should be alerted to the possibility of relapse in association with these conditions.

Adult↗

Circumstances surrounding relapse in a group of recent exsmokers.

This study examined the situational factors leading to relapse in a group of 69 smokers who quit and returned to smoking during a 1-year period following participation in a stop smoking clinic. Two-thirds of relapses occurred in the first 3 months after quitting, with the largest percentage (13/47 = 40%) occurring in the first week following cessation. Results showed that the circumstances leading to relapse varied as a function of the amount of time off of cigarettes. Among subjects relapsing in the first week after quitting, withdrawal symptoms and craving a cigarette was the most frequently cited reason for relapse. After the first week of cessation, coping with crisis situations and exposure to certain smoking triggers, such as the presence of other smokers and consumption of alcohol and coffee, were the main reasons given for relapse. The findings from this study suggest that pharmacologic influences associated with withdrawal from nicotine play an important role in early relapse, while psychosocial aspects of the smoking habit (i.e., coping with stress, other smokers) are the main causes of later relapse. The implications of these findings for relapse prevention are discussed.

Adult↗

The problem of neck relapse in early stage supraglottic cancer--results of different treatment modalities for the clinically negative neck.

We reviewed the records of patients with Stage I and II epidermoid carcinoma of the supraglottic larynx treated at the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, and at the Rotterdam Radio-Therapeutic Institute (RRTI), The Netherlands, between 1965 and 1979. At the MSKCC the treatment modality of choice for the primary tumor as well as for the neck had been surgery; of the 79 patients treated by surgery an elective neck dissection was performed on 31 patients. At the RRTI, however, the initial treatment for the primary tumor and the neck is radiation therapy. One-hundred and one patients were treated of whom 79% (80/101) had radiation therapy to the primary tumor as well as to both sides of the neck. This paper focuses on the problem of relapse in the neck, thus comparing patients treated in two large cancer centers by different treatment philosophies, that is elective neck dissection on one side of the neck versus elective radiation therapy to both sides of the neck. Twenty-nine percent of the patients from MSKCC (23/79) relapsed in the neck. The relapse rate was identical between the patients who did not have an elective radical neck dissection, and those who did. Among the patients who relapsed in the neck 65% (15/23) have died of the cancer, while among those who did not, none has died of supraglottic larynx cancer. Twenty-three percent (23/101) of the patients of the RRTI relapsed in the neck. Those who received radiation therapy to the primary tumor only relapsed regionally in 38% (8/21); treatment of both sides of the neck reduced the incidence of nodal recurrence to 19% (15/80). The majority of patients who relapsed in the neck eventually died of the cancer, that is 57% (13/23). Data from both institutions once again demonstrate the impact on survival of a relapse in the neck. Best strategies for decreasing the relapse rate in the neck are discussed; the conclusion was reached that, so far, elective radiation to both sides of the neck is the preferable treatment.

Adult↗

Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis.

Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.

Acyclovir↗

Trabecular and cortical bone as risk factors for orthodontic relapse.

INTRODUCTION: Dental relapse of the mandibular incisors after orthodontic treatment is a common problem, and few risk factors have been identified. The purpose of this case-control study was to evaluate whether the amount or the structure of mandibular bone affects the potential for postorthodontic mandibular incisor relapse. METHODS: The subject sample was selected from the postretention database at the University of Washington. Subjects were chosen based on the availability of lateral cephalograms and mandibular periapical radiographs taken approximately 10 years postretention (T3). The mandibular incisor irregularity index (II) was measured on the T3 casts. Two groups were identified: subjects with the II greater than 6 mm (relapse or case) and those with the II less than 3.5 mm (stable or control). Once the case/control status was determined, the II was measured on models taken at the initial orthodontic examination (T1) and at the end of treatment (T2). Sixty relapse and 263 stable subjects were identified. Mandibular cortical thickness measured on both panoramic and lateral cephalometric radiographs was used to assess the amount of mandibular bone, and fractal analysis was used to analyze the trabecular bone structure around the mandibular incisors on the periapical radiographs. Logistic regression analyses were used to determine the association between dental relapse and significant bone parameters. The models were adjusted for potentially confounding variables (initial II, sex, age, and postretention time). RESULTS: The relapse subjects had a larger mean II at T1 and a longer postretention time than the stable subjects. The mean cephalometric mandibular cortical thickness was significantly smaller in the relapse group than in the stable group at T1, T2, and T3. There were no statistically significant differences in the trabecular structure of bone, as measured with fractal analyses, between the relapse and stable groups. CONCLUSIONS: These results indicate that patients with thinner mandibular cortices are at increased risk for dental relapse.

Bone Density↗

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.

Adolescent↗

Risk factors and their effects on the dynamic process of smoking relapse among veteran smokers.

Smoking cessation programs can help smokers make a successful attempt at quitting, but many initial quitters relapse over time. This study aims to identify risk factors for smoking relapse and examine the influence of these factors on the dynamic relapse process in an outpatient smoking cessation program for veterans. Baseline information included socio-demographic description, medical and psychiatric comorbidities, smoking history and behavior, nicotine dependence, smoking motives, and confidence in the ability to quit. The intervention involved a 4-session group therapy consisting of cognitive and pharmacological treatments. The 189 initial quitters by program completion were followed via a telephone interview 6 months later. We identified six risk factors associated with relapse within the first 6 months post quit. Furthermore, we described characteristics of the dynamic process of smoking relapse and studied the influence of the identified risk factors on the relapse curve. The effects of these risk factors can be categorized into two patterns. Annual income and age at smoking initiation showed a delayed action that influenced the relapse curve after several weeks post quit, whereas age, number of smoking coworkers, history of schizophrenia, and number of sessions attended modified the relapse process soon after quitting. The information will be useful in targeting veteran smokers who are at high risk for relapse, choosing the optimal time for post-cessation services, and developing strategies accordingly.

Adult↗

Measurement of hepatitis B virus core-related antigen as predicting factor for relapse after cessation of lamivudine therapy for chronic hepatitis B virus infection.

BACKGROUND: Prolonged lamivudine therapy has two major problems: breakthrough hepatitis during treatment and relapse of aminotransferase (ALT) after cessation of the therapy. The aim of this study was to examine factors that could predict ALT flare after stopping lamivudine therapy. METHODS: We analyzed 22 Japanese patients with chronic hepatitis B infection, in whom lamivudine therapy was stopped after HBV DNA level had been gone undetectable (<3.7LGE/ml) during at least six consecutive months. The post-treatment followed up was carried for 28 months in median (range 9-41). HBV core-related antigen (HBcrAg) assay was assessed using newly developed assay. RESULTS: After cessation of lamivudine therapy, 11 patients (50%) had relapsed (reactivation of serum ALT >80IU/l, relapsers) and remaining 11 (50%) did not relapse (non-relapsers). In the univariate comparison of relapsers versus non-relapsers, HBcrAg level at lamivudine cessation point (4.5+/-1.0 versus 3.4+/-0.9; p=0.0145) has been shown as a significant predictive factor for non-relapse. All patients with HBcrAg <3.0logU/ml at the cessation point had no ALT flares. Multivariate analysis on effects of 10 factors (age, sex, cirrhosis, pretreatment ALT level, HBV DNA level, HBcrAg level, mean months till undetectable HBV DNA, duration of undetectable HBV DNA and HBcrAg level at lamivudine cessation point), indicated that HBcrAg level at lamivudine cessation point <3.4log U/ml was the only independent predictive factor for absence of the post-treatment relapse. CONCLUSIONS: HBcrAg level at lamivudine cessation point might be useful as a prognostic predictor of response to lamivudine therapy cessation. The measurement of HBcrAg is a useful additional test for monitoring chronic HBV infection.

Journal Article↗

Initial symptoms of manic relapse in manic or mixed-manic bipolar disorder: post hoc analysis of patients treated with olanzapine or lithium.

UNLABELLED: A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d). METHODS: Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse. RESULTS: A total of 31 patients relapsed during the first 3-16 weeks of the study (olanzapine, n=12; lithium, n=19). YMRS items that increased most frequently within a 2-week period preceding relapse were (olanzapine vs. lithium, respectively): increased motor activity/energy (58.3%, 21.1%), irritability (33.3%, 31.6%), decreased need for sleep (25.0%, 10.5%), increased speech (25.0%, 10.5%), and elevated mood (25.0%, 15.8%). YMRS items with significant odds ratios (OR) that predicted relapse in patients treated with olanzapine or lithium, respectively, were: increased motor activity/energy (OR, 35.7; OR, 7.8), irritability (OR, 9.5; OR, 7.8), elevated mood (OR, 8.1; OR, 4.2), and increased sexual interest (OR, 13.7; OR, 7.7). CONCLUSIONS: Early recognition of symptom exacerbation in bipolar mania, particularly increased motor activity-energy may permit clinical interventions to help avert relapse.

Acute Disease↗

A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients.

BACKGROUND: Cognitive predictors of relapse have been extensively explored only in few long term longitudinal studies of first-episode schizophrenia. METHOD: This study prospectively followed 93 patients with first-episode schizophrenia, schizophreniform disorder, and schizoaffective disorder for 3 years after their first-episode illness. Cognitive domains including verbal intelligence, verbal and visual memory, verbal fluency, and Wisconsin Card Sorting Test performance were investigated as potential predictors of relapse. RESULTS: We found that by the first year 21% patients had relapsed, by the second year 33% had relapsed, and by the third year 40% had relapsed. There was a significant difference in the relapse rate between patients with good adherence and patients with poor adherence to medication regimes. A multiple logistic regression analysis revealed that after controlling for medication adherence, perseverative error in the Wisconsin Card Sorting Test was the only cognitive function that significantly predict relapse with an odds ratio of 2.4. CONCLUSIONS: Cognitive flexibility in set shifting is related to tendency towards relapse in first-episode schizophrenic patients. Other cognitive factors appear not to be related to relapse. Possible mechanisms included the link between prefrontal dysfunction and sub-cortical dopamine system stability, as well as the effects of executive dysfunction on insight impairment and adherence behavior.

Adolescent↗

Serum concentrations of clozapine and norclozapine in the prediction of relapse of patients with schizophrenia.

Schizophrenic outpatients (n=102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p<0.001; CLZ+NCLZ: 225 ng/ml vs. 301 ng/ml, p<0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r=0.404, p<0.001) and the sum of CLZ and NCLZ (r=0.364, p<0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia.

Adolescent↗

Predictors of vaginal relapse in stage I endometrial cancer.

OBJECTIVE: To identify factors predictive of vaginal relapse in stage I endometrial cancer, thereby potentially facilitating the selection of patients who may benefit from vaginal brachytherapy. METHODS: The study population included 632 patients with stage I endometrial cancer managed with hysterectomy at our institution between 1984 and 1996. Median follow-up was 73 months; 122 patients (19%) received adjuvant radiotherapy. RESULTS: Overall, 2.9% of the stage I cohort developed vaginal relapse at 5 years. Vaginal relapse was observed in 1.7% of patients who received radiotherapy and in 3.0% of those whose treatment did not include radiotherapy (P = 0.36). Cox regression analysis (including radiotherapy) identified only grade 3 differentiation (hazard ratio = 3.83, P = 0.007) as an independent predictor of vaginal relapse. Patients with a low-grade tumor had a 5-year vaginal relapse rate of 2%, compared with 7% for those with a grade 3 tumor. When only patients who did not receive adjuvant radiotherapy were considered, both grade 3 tumor and lymphovascular invasion were significant predictors of vaginal relapse (P < 0.05). When neither variable was present, 2% of patients experienced vaginal relapse at 5 years, compared with 11% when either 1 was present (P < 0.001). Depth of myometrial invasion was not a significant predictor of vaginal recurrence. CONCLUSION: Histologic grade 3 tumor and lymphovascular invasion were the cogent predictors of vaginal relapse in our population. The cost and morbidity of vaginal brachytherapy should be balanced against the potential risk of vaginal relapse in this group of patients.

Cohort Studies↗

Delayed visual NA potential in remitted schizophrenia: a new vulnerability marker for psychotic relapse under low-dose medication.

BACKGROUND: Lasting cognitive dysfunction throughout remission has been regarded as a biological vulnerability in schizophrenia, which may produce psychotic relapses with characteristic symptoms. Our hypothesis was that an abnormality in event-related potentials (ERPs) may be a neurophysiological marker of vulnerability to psychotic relapse in remitted schizophrenia. We conducted a 2-year follow-up study after evaluating ERP abnormalities to find a new ERP marker for schizophrenic relapse. METHODS: Visual ERPs were recorded from outpatients with remitted schizophrenia under maintenance pharmacotherapy (n = 44) and normal controls (n = 20) during a letter discrimination task. Based on the prospective study, the patients were divided into a relapse group (n = 20) and a nonrelapse group (n = 24). ERP findings that related to psychotic relapse within 2 years were analyzed. RESULTS: Compared with controls, the relapsers showed ERP abnormalities in the NA, N2, and P3 components, and the nonrelapsers in the P3 component. The peak latency of the NA potential was delayed significantly in the relapse group relative to the nonrelapse group, and predicted a psychotic relapse with about 90% probability. CONCLUSIONS: The delayed NA, which reflects early perceptual disorganization, may be a promising neurophysiological predictor of psychotic relapse in remitted schizophrenia under maintenance pharmacotherapy.

Adult↗

[Relapse prevention group therapy for paedophiles: French adaptation].

Psychotherapy for sex offenders has only very recently started to develop in France. The French law on compulsory treatment for sex offenders was voted in 1998, and many mental health practitioners are not trained to treat such patients yet. In our ambulatory forensic consultation, sex offenders have been treated since 1992 and group psychotherapy has been offered to them since 1994. Our first therapeutic models were the North-American behavioural-cognitive therapy and Pithers' relapse prevention model. Behavioural-cognitive theory describes paedophilia as an acquired sexual preference maintained by positive reinforcement. Pithers (1990) considered that relapse only occurs in high-risk situations, and that high-risk situations always come after offence precursors. In North America, relapse prevention consists in helping paedophiles spot their high-risk situations and offence precursors, and enhance their skills to cope with such situations or to prevent them. Therapy programs were developed according to these models, aiming to help offenders develop such skills, ie empathy, social skills, cognitive restructuring, self-esteem, etc. Trying to apply these therapy programs in France, our team quickly realised that we would have to adapt them to French culture. On the one hand, behavioural-cognitive theory did not seem satisfactory enough in explaining paedophilic behaviour and paedophilic preference. On the other hand, behavioural-cognitive therapy made patients into children too much and increased resistance. Therapy based on programs seemed too rigid for French patients and therapists, and we often felt we were working on an issue that would have been much more accurate to work on a few sessions earlier, when this issue was spontaneously brought up by a patient. We believe change occurs all the more as issues are worked on at the right moment for the patient. Moreover, on a cultural point of view, we also realised the use of programs in psychotherapy was difficult to accept in France both by patients and therapists, as our culture is strongly influenced by psychoanalysis, especially free association. The use of a plethysmograph was also impossible in our country. We thus decided to use Pithers' relapse prevention model but to let our patients free to speak, so our therapy was not a program. Offences were analysed according to Pithers' ideas about high-risk situations and offence precursors. Most of the sessions were non-directive, but therapists offered each patient to work on his offence when they believed it was the right moment. Important issues (such as empathy, cognitive distortions, emotional control, etc.), were tackled as they came up, which seemed easier and less rigid as sessions were linked to patients' current pre- occupations. Post-group meetings enabled therapists to draw themes that seemed important to work on with each patient (empathy, consequences on victims, anger, cognitive distortions, emotional expression, relational issues, self-esteem, intimacy...). These issues were discussed the next time they were raised by the group. We were interested to notice that all important issues came up spontaneously from the group during the sessions as long as patients were free to share their concerns, without therapists having to set issues beforehand. Two case studies illustrate our method. Bernard was 40 when he first came to our consultation. Originally a teacher, he was dismissed and became a marketing man after being sentenced to five years of prison for sex offences on two 6-year-old girls. Bernard relapsed a few years after he got out of prison by sexually offending two girls, aged 10 and 13. At our first interview, Bernard had cognitive distortions about sexual education and always avoided sexually explicit words to describe the offences. He did not realise the consequences of his acts on the victims, but said he wanted to be treated because he felt lonely. He first described a sexual preference for adult women, but progressively aknoledged feeling attracted to female teenagers. He did not know why the offences occurred at such a moment in his life, and had no idea of his high-risk situations nor of his offence precursors. Bernard often confused his need for sex and his need for affection. After four years' participation to our relapse prevention group therapy, Bernard has clarified his sexual preferences : he has always been mostly attracted to girls from 6 to 10 years old. He has also always been attracted to women younger than him, and now seems to be mostly aroused by female teenagers. Working on his offences has helped him identify his high-risk situations and the strategies he used to get close to his victims and to be trusted by them and their single mothers. Bernard often offended when he was feeling lonely and rejected, after a break-up with a partner. Twice during these four years, Bernard found himself in such high-risk situations, but managed to stop before relapsing. However, empathy towards victims is still difficult to develop for Bernard. Neither has he yet managed to build a new relationship with a woman, as he still seems to suffer from an unhappy love affair he went through several years ago. This case study shows one of the limits of Pithers' relapse prevention model, if it is used mechanically. Indeed, we should logically have spotted as high-risk situations for Bernard interactions with 6 to 10 year-old girls. Helping him face his past and present sexual fantasies led Bernard realise his high-risk situations were now mainly about teenage girls, even if he had mostly been attracted to younger girls earlier in his life. After 2 to 3 years of therapy, we have quite often noticed this kind of evolution in sexual preferences in paedophiles, their preferences changing towards teenagers or young adults. In France, mental health professionals are often reluctant to follow sex offenders because of negative counter-transference and lack of specific training. However, first changes often occur quite quickly in paedophiles when they are offered group therapy. The group makes it easier to confront paedophiles to the reality of their offence and of their sexual fantasies. These patients often express being very relieved after the first sessions, as the group therapy is generally their first opportunity to express their feelings, sexual fantasies and thoughts about paedophilia. Pithers' model, used within a group were patients are free to speak in a human, warm and confronting atmosphere, seems clinically accurate and effective in helping paedophiles in France. We now need studies to check therapy effectiveness on relapse and to understand which therapy factors are efficient on sex offenders.

Adult↗

Polyunsaturated fatty acid status and relapse vulnerability in cocaine addicts.

There is mounting evidence that low levels of some polyunsaturated fatty acids (PUFAs) play a role in the pathophysiology of depressive and aggressive disorders, including homicides. There is also evidence derived mostly from the animal literature that PUFAs could play a role in the abuse of substances through their action on central serotonergic and dopaminergic systems that are both known to play a role in reward mechanisms. In this study, we explored the possibility that the relapse rates of cocaine addicts discharged after a period of detoxification on an inpatient unit would be associated with their PUFA status. Thirty-eight patients were enrolled in the study. PUFA status was assessed only at baseline, shortly after admission. Resumption of substance use was assessed 3 months, 6 months and 1 year following discharge. Thirty-two patients remained available for follow-up for the duration of the study. Subjects who relapsed at 3 months had significantly lower baseline levels of total n-6 PUFAs, linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) and total n-3 PUFAs when compared to non-relapsers by ANCOVAs with age and weight as covariates. Lower baseline total n-6 PUFAs, LA and AA continued to predict relapse 6 months and 12 months following discharge. Age, marital status, educational level, cocaine use parameters or psychopathology did not differ between relapsers and non-relapsers. In conclusion, low PUFA status at baseline was a better predictor of relapse than cocaine use, sociodemographic or clinical parameters. These data suggest, but do not prove, the existence of a causal relationship between n-6 or n-3 status and relapse vulnerability in cocaine addicts, and provide a rationale for the exploration of possible relationships between relapse to addictive disorders and PUFA status in observational and interventional trials.

Adult↗