Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study.

PubMed

Chaoui, Driss; Choquet, Sylvain; Sanhes, Laurence; Mahé, Béatrice; Hacini, Maya; Fitoussi, Olivier; Arkam, Yazid; Orfeuvre, Hubert; Dilhuydy, Marie-Sarah; Barry, Marly; Jourdan, Eric; Dreyfus, Brigitte; Tempescul, Adrian; Leprêtre, Stéphane; Bardet, Aurélie; Leconte, Pierre; Maynadié, Marc; Delmer, Alain

2017-06-01

This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.

Positive Surgical Margins in Favorable-Stage Differentiated Thyroid Cancer.

PubMed

Mercado, Catherine E; Drew, Peter A; Morris, Christopher G; Dziegielewski, Peter T; Mendenhall, William M; Amdur, Robert J

2018-04-16

The significance of positive margin in favorable-stage well-differentiated thyroid cancer is controversial. We report outcomes of positive-margin patients with a matched-pair comparison to a negative-margin group. A total of 25 patients with classic-histology papillary or follicular carcinoma, total thyroidectomy +/- node dissection, stage T1-3N0-1bM0, positive surgical margin at primary site, adjuvant radioactive iodine (I-131), and age older than 18 years were treated between 2003 and 2013. Endpoints were clinical and biochemical (thyroglobulin-only) recurrence-free survival. Matched-pair analysis involved a 1:1 match with negative-margin cases matched for overall stage and I-131 dose. Recurrence-free survival in positive-margin patients was 71% at 10 years. No patient was successfully salvaged with additional treatment. Only 1 patient died of thyroid cancer. Recurrence-free survival at 10 years was worse with a positive (71%) versus negative (90%) margin (P=0.140). Cure with a microscopically positive margin was suboptimal (71%) despite patients having classic-histology papillary and follicular carcinoma, favorable stage, and moderate-dose I-131 therapy.

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

Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group.

PubMed

Sung, Lillian; Aplenc, Richard; Alonzo, Todd A; Gerbing, Robert B; Wang, Yi-Cheng; Meshinchi, Soheil; Gamis, Alan S

2016-11-01

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non-Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five hundred and sixty-nine patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54-204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, p = 0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy. © 2016 UICC.

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

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.

The risk of central nervous system relapses in patients with peripheral T-cell lymphoma

PubMed Central

Fanale, Michelle A.; Miranda, Roberto N.; Noorani, Mansoor; Westin, Jason R.; Nastoupil, Loretta J.; Hagemeister, Fredrick B.; Fayad, Luis E.; Romaguera, Jorge E.; Samaniego, Felipe; Turturro, Francesco; Lee, Hun J.; Neelapu, Sattva S.; Rodriguez, M. Alma; Wang, Michael; Fowler, Nathan H.; Davis, Richard E.; Medeiros, L. Jeffrey; Oki, Yasuhiro

2018-01-01

We performed a retrospective analysis to identify risk factors and survival outcome for central nervous system (CNS) relapse of peripheral T-cell lymphoma (PTCL) by histologic type. Records of 600 PTCL patients diagnosed between 1999 and 2014 were analyzed including PTCL not otherwise specified (PTCL-NOS, 174 patients), angoimmunoblastic T-cell lymphoma (AITL, 144), ALK+anaplastic large cell lymphoma (ALCL, 74), ALK-ALCL (103), extranodal NK-cell lymphoma (ENKL, 54), or others (51). With a median follow up of 57 months, 13 patients (4 PTCL-NOS, 1 AITL, 4 ALK+ALCL, 2 ALK-ALCL, 2 ENKL) experienced CNS relapse. One-year and 5-year cumulative incidence of CNS relapse were 1.5% (95%CI: 0.7–2.8%) and 2.1% (95%CI: 1.1–3.5%), respectively. The 5-year cumulative incidence of CNS relapse was 1.8% in PTCL-NOS, 0.7% in AITL, 5.4% in ALK+ALCL, 2.1% in ALK-ALCL and 3.7% in ENKL. Extranodal involvement >1 site was the only significant factor associated with higher chance of CNS relapse (HR: 4.9, 95%CI: 1.6–15.0, p = 0.005). Patients with ALK+ALCL who had extranodal involvement >1 (N = 19) had very high risk of CNS relapse with one year cumulative incidence of 17% (95%CI: 4%-37%), all occurring within six months after diagnosis. All patients with CNS relapse eventually died (median, 1.5 months; range, 0.1–10.1 months). CNS relapse in patients with PTCL is rare event but the risk varies by subtype. ALK+ALCL patients with extranodal involvement >1 site have a very high risk of early CNS relapse, and thus evaluation of CNS involvement at the time of diagnosis and possible CNS-directed prophylaxis may be considered. PMID:29538376

Locally limited inhibition of bone resorption and orthodontic relapse by recombinant osteoprotegerin protein.

PubMed

Schneider, D A; Smith, S M; Campbell, C; Hayami, T; Kapila, S; Hatch, N E

2015-04-01

To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein (OPG-Fc), while also determining effects of injected OPG-Fc on alveolar bone and long bone. The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats. Maxillary molars were moved with nickel-titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and femur bone. Local injection of OPG-Fc inhibited molar but not incisor relapse, when compared to vehicle-injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse. Our results demonstrate that a single local injection of OPG-Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG-Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG-Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Prognostic Factors, Treatment, and Outcomes in Early Stage, Invasive Papillary Breast Cancer: A SEER Investigation of Less Aggressive Treatment in a Favorable Histology.

PubMed

Fakhreddine, Mohamad H; Haque, Waqar; Ahmed, Awad; Schwartz, Mary R; Farach, Andrew M; Paulino, Arnold C; Bonefas, Elizabeth; Miltenburg, Darlene; Niravath, Polly; Butler, E Brian; Teh, Bin S

2018-06-01

Invasive papillary breast cancer (IPBCA) represents 0.5% of invasive BCA, and is thought to carry a favorable prognosis. This population-based study reports on prognostic factors, treatment, and outcomes of early-stage IPBCA to explore whether there is any evidence to support less aggressive treatment. IPBCA cases from 1990 to 2009 of the recent Surveillance, Epidemiology, and End Results were analyzed. Inclusion criteria included patients with stage T1-2, N0 IPBCA. Univariate and multivariate analyses were performed using the variables of treatment, stage, race, hormone receptor status, grade (G1-3), and age. Treatment modalities included lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), and mastectomy alone (MA). Among 10,485 patients, median follow-up was 56 months. Five and 10-year overall survival (OS) were 93.1% and 76.8%, respectively. Patients treated with LRT had superior mean OS 16.8 versus 14.9 years for MA (P=0.0004) and 14.2 years for LA (P=0.0003). Improved OS also correlated with lower histologic grade (P<0.0001), lower T-stage (P<0.0001), and younger age (P<0.0001). Black patients had the worst OS (12.7 y, P<0.0001). LRT is associated with superior OS for early-stage invasive papillary BCA patients, when compared with LA or MA in this population-based study. The findings support the standard of care breast conservation approach for patients with invasive papillary BCA. Other prognostic factors associated with worse OS include increased age, higher T-stage, higher histologic grade, and black race.

Successful treatment with biweekly CHOP for bone marrow relapse of blastic plasmacytoid dendritic cell neoplasm.

PubMed

Ono, Keiko; Ise, Mikiko; Ikebe, Dai; Sato, Akiyasu; Wang, Xiaofei; Sugawara, Takeaki; Tsujimura, Hideki; Itami, Makiko; Kumagai, Kyoya

2017-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. The majority of patients initially respond to multi-agent chemotherapy, though most relapse within a year and the prognosis is very poor. We report a 67-year-old man with erythema on the right chest and a nasopharyngeal mass. Histological examination revealed a mass of tumor cells expressing CD4, CD56, and CD123, but neither CD3 nor CD20. He was diagnosed with BPDCN. Bone marrow involvement was not seen at diagnosis. He achieved complete remission (CR) with CHOP-like chemotherapy. After 1 year, he relapsed with a cutaneous tumor on the head, a nasopharyngeal tumor, and massive bone marrow involvement. Relapsed BPDCN is generally resistant to chemotherapy and the prognosis is dismal. However, he was successfully treated with biweekly CHOP therapy and achieved a second CR lasting 16 months.

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

Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

PubMed

Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

2016-06-01

Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

PubMed

Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

2015-01-08

Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

Outcome of older patients with acute myeloid leukemia in first relapse.

PubMed

Sarkozy, Clémentine; Gardin, Claude; Gachard, Nathalie; Merabet, Fathia; Turlure, Pascal; Malfuson, Jean-Valère; Pautas, Cécile; Micol, Jean-Baptiste; Thomas, Xavier; Quesnel, Bruno; Celli-Lebras, Karine; Preudhomme, Claude; Terré, Christine; Fenaux, Pierre; Chevret, Sylvie; Castaigne, Sylvie; Dombret, Hervé

2013-09-01

To provide data for future drug evaluation, we analyzed the outcome of 393 patients aged 50 years or older (median, 64 years) with AML in first relapse after treatment in recent ALFA trials. Salvage options were retrospectively classified as follows: best supportive care (BSC), low-dose cytarabine (LDAC), gemtuzumab ozogamicin (GO), intensive chemotherapy (ICT), or ICT combined with GO. Second complete remission (CR2) rate was 31% and median post-relapse survival was 6.8 months (0, 17, 42.5, 53, and 80% and 3.2, 5.6, 8.9, 9, and 19.8 months in BSC, LDAC, GO, ICT, and ICT + GO subsets, respectively). Age, performance status, WBC, CR1 duration, and favorable AML karyotype, but not other cytogenetic or molecular features, influenced post-relapse outcome. Multivariate adjustment and propensity score matching showed that intensive salvage (ICT/ICT+GO/GO versus LDAC/BSC) was associated with longer post-relapse survival, at least in patients with CR1 duration ≥12 months (P = 0.001 and 0.0005, respectively). Of interest, GO appeared to be as effective as standard ICT, and ICT + GO combination more effective than standard ICT. In conclusion, older patients with CR1 duration ≥12 months appeared to benefit from intensive salvage and results observed with GO-containing salvage suggest that GO combination studies should be actively pursued in this setting. Copyright © 2013 Wiley Periodicals, Inc.

[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.

Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome?

PubMed

Katodritou, E; Gastari, V; Verrou, E; Hadjiaggelidou, C; Varthaliti, M; Georgiadou, S; Laschos, K; Xirou, P; Yiannaki, E; Constantinou, N; Markala, D; Zervas, K

2009-08-01

Extramedullary relapse constitutes an uncommon manifestation of multiple myeloma (MM), characterized by highly malignant histology, special biological features, resistance to treatment and poor outcome. Its incidence has been increased during the last years, probably due to the introduction of novel strategies in the management of MM, including intensified treatment and immunomodulatory drugs. Here we report nine cases of extramedullary relapse of MM, presented in unusual locations, seven of which had previously been treated with thalidomide-containing regimens (TCR). Our aim was to explore the morphological, immunophenotypical, molecular and laboratory characteristics accompanying EMP-relapse and seek possible correlations with treatment and clinical outcome.

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

The Risk of Relapse after Anti-TNF Discontinuation in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

PubMed

Gisbert, Javier P; Marín, Alicia C; Chaparro, María

2016-05-01

To perform a meta-analysis of the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC), to evaluate risk factors for relapse, and to assess the response to retreatment with the same anti-TNF. Studies evaluating the incidence of relapse after anti-TNF discontinuation in patients with CD or UC who reached clinical remission with anti-TNFs were included. Bibliographies up to January 2015 were searched. Frequency of relapse after discontinuation of anti-TNF agents was determined; meta-analyses were performed using the inverse-variance method. We included 27 studies (21 infliximab and 6 infliximab/adalimumab). The overall risk of relapse after discontinuation of anti-TNF therapy was 44% for CD (95% confidence interval (CI) 36-51%; I(2)=79%; 912 patients) and 38% for UC (23-52%; I(2)=82%; 266 patients). In CD, the relapse rate was 38% at 6 months after discontinuation (short term), 40% at 12 months (medium term), and 49% at >25 months (long term). In UC, 28% of patients relapsed at 12 months. In CD, when clinical remission was the only criterion for stopping anti-TNF therapy, the relapse rate after 1 year was 42%, which decreased to 26% when endoscopic remission was also required. Retreatment with the same anti-TNF induced remission again in 80% of cases (68-91%). Approximately one-third of patients with inflammatory bowel disease in remission under anti-TNF treatment relapsed 1 year after discontinuation. This proportion increased to half in the long term. In CD patients, the risk of relapse was lower when the criterion for discontinuation was endoscopic remission and not only clinical remission. Response to retreatment with the same anti-TNF agent was favorable.

Predicting Relapse among Young Adults: Psychometric Validation of the Advanced Warning of Relapse (AWARE) Scale

PubMed Central

Kelly, John F.; Hoeppner, Bettina B.; Urbanoski, Karen A.; Slaymaker, Valerie

2011-01-01

Objective Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure - the Advance WArning of RElapse scale (AWARE) scale (Miller and Harris, 2000) in an understudied but clinically important sample of young adults. Method Inpatient youth (N=303; Age 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Results Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. Conclusions The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. PMID:21700396

Predicting relapse among young adults: psychometric validation of the Advanced WArning of RElapse (AWARE) scale.

PubMed

Kelly, John F; Hoeppner, Bettina B; Urbanoski, Karen A; Slaymaker, Valerie

2011-10-01

Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure-the Advance WArning of RElapse (AWARE) scale (Miller & Harris, 2000) in an understudied but clinically important sample of young adults. Inpatient youth (N=303; Ages 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment. Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors. The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Meta-analysis of gene expression profiles associated with histological classification and survival in 829 ovarian cancer samples.

PubMed

Fekete, Tibor; Rásó, Erzsébet; Pete, Imre; Tegze, Bálint; Liko, István; Munkácsy, Gyöngyi; Sipos, Norbert; Rigó, János; Györffy, Balázs

2012-07-01

Transcriptomic analysis of global gene expression in ovarian carcinoma can identify dysregulated genes capable to serve as molecular markers for histology subtypes and survival. The aim of our study was to validate previous candidate signatures in an independent setting and to identify single genes capable to serve as biomarkers for ovarian cancer progression. As several datasets are available in the GEO today, we were able to perform a true meta-analysis. First, 829 samples (11 datasets) were downloaded, and the predictive power of 16 previously published gene sets was assessed. Of these, eight were capable to discriminate histology subtypes, and none was capable to predict survival. To overcome the differences in previous studies, we used the 829 samples to identify new predictors. Then, we collected 64 ovarian cancer samples (median relapse-free survival 24.5 months) and performed TaqMan Real Time Polimerase Chain Reaction (RT-PCR) analysis for the best 40 genes associated with histology subtypes and survival. Over 90% of subtype-associated genes were confirmed. Overall survival was effectively predicted by hormone receptors (PGR and ESR2) and by TSPAN8. Relapse-free survival was predicted by MAPT and SNCG. In summary, we successfully validated several gene sets in a meta-analysis in large datasets of ovarian samples. Additionally, several individual genes identified were validated in a clinical cohort. Copyright © 2011 UICC.

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.

[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.

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

PubMed Central

Cohan, Stanley

2016-01-01

Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

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.

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.

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.

Late Relapse of Classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7 to HD12 Trials.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Kohnhorst, Charlotte; von Tresckow, Bastian; Moccia, Alden; Markova, Jana; Meissner, Julia; Kerkhoff, Andrea; Ludwig, Wolf-Dieter; Fuchs, Michael; Borchmann, Peter; Engert, Andreas

2017-05-01

Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared

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.

Case report: retroperitoneal fibrosis simulating local relapse of sarcomatoid renal cell carcinoma.

PubMed

Esquena, Salvador; Abascal, José Maria; Trilla, Enrique; De Torres, Inés; Morote, Juan

2006-01-01

Generally, retroperitoneal fibrosis is an idiopathic process that envelopes and displaces ureters, causing hydronefrosis and renal failure. CT scan is the best choice for diagnosis. Other aetiologies described are malignancies, drugs, aorta aneurisms and immunological or rheumatological diseases. A 53-year-old male with hypertension and diabetes was operated on radical nephrectomy for renal mass. Pathological examination showed sarcomatoid renal cell carcinoma, Fürhman 3 grade, pT2 N0. Within 6 months of surgery, control CT scan demonstrated a left retroperitoneal mass, without separation with pancreas queue and spleen hilium, suggesting local relapse. Resection of the mass with splenectomy and partial pancreatectomy en bloc was performed. Microscopic evaluation revealed a dense collagenic tissue with a prominent inflammatory infiltrate, and the immunohistochemical study was negative for cytokeratin AE1-AE3. There was no evidence of malignancy in the histological examination. All these findings aided to diagnose a retroperitoneal fibrosis. Sometimes retroperitoneal fibrosis can simulate or is associated to malignancies. Presentation of a retroperitoneal fibrosis simulating local relapse of sarcomatoid renal cell carcinoma has not been previously reported in the English literature.

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

PubMed

Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

2016-07-01

The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Individualized relapse prediction: Personality measures and striatal and insular activity during reward-processing robustly predict relapse.

PubMed

Gowin, Joshua L; Ball, Tali M; Wittmann, Marc; Tapert, Susan F; Paulus, Martin P

2015-07-01

Nearly half of individuals with substance use disorders relapse in the year after treatment. A diagnostic tool to help clinicians make decisions regarding treatment does not exist for psychiatric conditions. Identifying individuals with high risk for relapse to substance use following abstinence has profound clinical consequences. This study aimed to develop neuroimaging as a robust tool to predict relapse. 68 methamphetamine-dependent adults (15 female) were recruited from 28-day inpatient treatment. During treatment, participants completed a functional MRI scan that examined brain activation during reward processing. Patients were followed 1 year later to assess abstinence. We examined brain activation during reward processing between relapsing and abstaining individuals and employed three random forest prediction models (clinical and personality measures, neuroimaging measures, a combined model) to generate predictions for each participant regarding their relapse likelihood. 18 individuals relapsed. There were significant group by reward-size interactions for neural activation in the left insula and right striatum for rewards. Abstaining individuals showed increased activation for large, risky relative to small, safe rewards, whereas relapsing individuals failed to show differential activation between reward types. All three random forest models yielded good test characteristics such that a positive test for relapse yielded a likelihood ratio 2.63, whereas a negative test had a likelihood ratio of 0.48. These findings suggest that neuroimaging can be developed in combination with other measures as an instrument to predict relapse, advancing tools providers can use to make decisions about individualized treatment of substance use disorders. Published by Elsevier Ireland Ltd.

Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database.

PubMed

Saltzman, A F; Carrasco, A; Amini, A; Aldrink, J H; Dasgupta, R; Gow, K W; Glick, R D; Ehrlich, P F; Cost, N G

2018-04-01

There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P = 0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee

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.

Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

PubMed

Mangiacavalli, Silvia; Pochintesta, Lara; Pascutto, Cristiana; Cocito, Federica; Pompa, Alessandra; Cazzola, Mario; Corso, Alessandro

2013-02-01

Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase. Copyright © 2012 Wiley Periodicals, Inc.

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

Outcomes of Children With Favorable Histology Wilms Tumor and Peritoneal Implants Treated in National Wilms Tumor Studies-4 and -5

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

Kalapurakal, John A., E-mail: j-kalapurakal@northwestern.ed; Green, Daniel M.; Haase, Gerald

Purpose: There are no published reports on the optimal management and survival rates of children with Wilms tumor (WT) and peritoneal implants (PIs). Methods and Materials: Among favorable histology WT patients enrolled in the National Wilms Tumor Study (NWTS)-4 and NWTS-5, 57 children had PIs at the time of nephrectomy. The median age was 3 years 5 months (range, 3 months to 14 years). The majority of children (42 of 57 [74%)] had Stage III tumors; 15 had Stage IV disease. All patients received multimodality therapy. Of 56 children who underwent primary surgery, 48 (84%) had gross total resection ofmore » all tumors. All patients received 3-drug chemotherapy with vincristine, dactinomycin, and doxorubicin. Whole-abdomen radiotherapy (RT) was used in 47 patients (82%), and in 50 patients (88%) the RT dose was 10.5 Gy. Results: After a median follow-up of 7.5 years, the overall abdominal and systemic tumor control rates were 97% and 93%, respectively. A comparative analysis between children with PIs and those without PIs showed no significant differences in the clinical characteristics between the two groups. The 5-year event-free survival rates with and without PIs were 90% (95% confidence interval, 78-96%) and 83% (95% confidence interval, 81-85%) respectively (p = 0.20). Conclusions: Multimodality therapy with surgery, whole-abdomen RT, and three-drug chemotherapy delivered according to the NWTS-4 and -5 protocols resulted in excellent abdominal and systemic tumor control rates. All children should be monitored in long-term surveillance programs for the early detection and management of therapy-related toxicities.« less

The Wisconsin Predicting Patients' Relapse questionnaire

PubMed Central

Bolt, Daniel M.; McCarthy, Danielle E.; Japuntich, Sandra J.; Fiore, Michael C.; Smith, Stevens S.; Baker, Timothy B.

2009-01-01

Introduction: Relapse is the most common smoking cessation outcome. Accurate prediction of relapse likelihood could be an important clinical tool used to influence treatment selection or duration. The aim of this research was to develop a brief clinical relapse proneness questionnaire to be used with smokers interested in quitting in a clinical setting where time is at a premium. Methods: Diverse items assessing constructs shown in previous research to be related to relapse risk, such as nicotine dependence and self-efficacy, were evaluated to determine their independent contributions to relapse prediction. In an exploratory dataset, candidate items were assessed among smokers motivated to quit smoking who enrolled in one of three randomized controlled smoking cessation trials. A cross-validation dataset was used to compare the relative predictive power of the new instrument against the Fagerström Test for Nicotine Dependence (FTND) at 1-week, 8-week, and 6-month postquit assessments. Results: We selected seven items with relatively nonoverlapping content for the Wisconsin Predicting Patient's Relapse (WI-PREPARE) measure, a brief, seven-item questionnaire that taps physical dependence, environmental factors, and individual difference characteristics. Cross-validation analyses suggested that the WI-PREPARE demonstrated a stronger prediction of relapse at 1-week and 8-week postquit assessments than the FTND and comparable prediction to the FTND at a 6-month postquit assessment. Discussion: The WI-PREPARE is easy to score, suggests the nature of a patient's relapse risk, and predicts short- and medium-term relapse better than the FTND. PMID:19372573

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

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.

Histological changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in high-risk prostate cancer patients

PubMed Central

O’Brien, Catherine; True, Lawrence D.; Higano, Celestia S.; Rademacher, Brooks L. S.; Garzotto, Mark; Beer, Tomasz M.

2011-01-01

Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high risk prostate cancer. Little is known about the clinical significance of post-chemotherapy tumor histopathology. We assessed the prognostic and predictive value of histological features (intraductal carcinoma, vacuolated cell morphology, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with pre-prostatectomy docetaxel and mitoxantrone. At a median follow-up of 65 months, the overall relapse-free survival (RFS) at 2 and 5 years was 65% and 49%, respectively. In univariate analyses (using Kaplan-Meier method and log-rank tests) intraductal (p=0.001) and cribriform (p=0.014) histologies were associated with shorter RFS. In multivariate analyses, using Cox’s proportional hazards regression, baseline PSA (p=0.004), lymph node metastases (p<0.001), and cribriform histology (p=0.007) were associated with shorter RFS. In multivariable logistic regression analysis, only intraductal pattern (p=0.007) predicted lymph node metastases. Intraductal and cribriform histologies apparently predict post-chemotherapy outcome. PMID:20231619

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.

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.

[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

Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: What is the role of elective neck irradiation?

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

Chen, Allen M.; Garcia, Joaquin; Lee, Nancy Y.

2007-03-15

Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinomamore » (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.« less

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

A trabecular metal implant 4 months after placement: clinical-histologic case report.

PubMed

Spinato, Sergio; Zaffe, Davide; Felice, Pietro; Checchi, Luigi; Wang, Hom-Lay

2014-02-01

The aim of this case report was to histologically evaluate the behavior of a trabecular metal (TM) implant composed of titanium and spatial 3-dimensional tantalum (Ta) trabeculae. This study is the first human histologic case report of this implant. A TM implant was placed in a 54-year-old woman exhibiting moderate chronic periodontitis. After periodontal treatment, the implant was inserted under favorable clinical conditions. Patient was not seen for 4 months because of unrelated breast reduction surgery. At the surgical reopening, periimplant inflammation affecting the coronal third of the implant was observed 4 months after implant placement. With patient's consent, the implant was removed for histologic analysis. Histology highlighted a greater amount of bone in close contact with Ta trabeculae than titanium surfaces. The finding of bone formation around the Ta trabeculae suggests that trabecular metal material promotes bone ingrowth for secondary implant stability. Additional evidence is needed to confirm this observation.

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…

Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective "Lymphomes Malins B" protocols. A Société Française des Cancers de l'Enfant study.

PubMed

Jourdain, Anne; Auperin, Anne; Minard-Colin, Véronique; Aladjidi, Nathalie; Zsiros, Josef; Coze, Carole; Gandemer, Virginie; Bertrand, Yves; Leverger, Guy; Bergeron, Christophe; Michon, Jean; Patte, Catherine

2015-06-01

To describe relapsed B-cell lymphoma or leukemia in children/adolescents treated with a "Lymphomes Malins B" regimen and their outcome and to identify prognostic factors for survival, we studied relapses in the LMB89, 96 and 2001 studies of the Société Française d'Oncologie Pédiatrique (Société Française des Cancers de l'Enfant). Therapeutic guidelines at relapse were to obtain a second complete remission and to consolidate the remission with high-dose chemotherapy followed by autologous stem-cell transplantation. Between July 1989 and March 2007, 67 patients of 1322 (5%) relapsed: 57 had Burkitt lymphoma and 10 had large-cell histology. Three patients were initially treated in risk group A, 41 in group B and 23 in group C. Thirty-three patients had a relapse in one site (15 in the central nervous system) and 34 at multiple sites. Sixty-five patients received salvage chemotherapy and 33 achieved complete remission. Forty-one patients also received high-dose chemotherapy followed by autologous (n=33) or allogeneic (n=8) transplantation. With a median follow-up of 6.4 years, the 5-year survival rate was 29.9%. Nineteen patients were still alive, all but one (group A) received consolidation treatment. Multivariate analysis showed the following factors to be significantly associated with better survival: relapse at one site (P=0.0006), large-cell histology (P=0.012), initial prognostic group A or B with lactate dehydrogenase level below twice the normal value (P=0.005), and time to relapse more than 6 months (P=0.04). Copyright© Ferrata Storti Foundation.

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.

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

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.

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

PubMed Central

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

2011-01-01

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

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.

Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

PubMed

Guardiola, Jordi; Lobatón, Triana; Rodríguez-Alonso, Lorena; Ruiz-Cerulla, Alexandra; Arajol, Claudia; Loayza, Carolina; Sanjuan, Xavier; Sánchez, Elena; Rodríguez-Moranta, Francisco

2014-11-01

Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

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

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 phase II study of high-dose celecoxib and metronomic 'low-dose' cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma.

PubMed

El Bary, Naser Abd; Hashem, Tarek; Metwally, Hasan; Ghany, Ashraf Abd; El Mageed, Hager Abd

2010-01-01

Relapsed, histologically aggressive non-Hodgkin lymphoma (NHL) has a poor prognosis; relapsed patients who do not respond to second line therapy or are unfit for BMT have a worse prognosis. Angiogenesis is increased in aggressive NHL and could be targeted by selective cyclooxygenase-2 inhibition and metronomic chemotherapy. We assessed the toxicity of metronomic chemotherapy and the response and progression-free survival in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We prospectively studied 41 patients with a diagnosis of relapsed and/or refractory DLBCL who may have received any number of preceding therapies (as long as one included an anthracycline) and were not candidates for bone marrow transplantation. They received oral cyclophosphamide (50 mg every day), oral methotrexate (2.5 mg 4 times/week) and high-dose oral celecoxib (400 mg twice daily) until there was disease progression or unacceptable toxicity. All 41 patients (median age, 56 years) were evaluable for toxicity and response, with a median follow up of 9.1 months (range, 4-35 months). At relapse, 51.2% had a high international prognostic index. The treatment protocol was well tolerated with no major toxicities. The most common toxicities were fatigue (61%), nausea (22%), neutropenia (19.5%), and anemia (22%). In 31.7% there was a partial response and 48.8% had stable disease. Progression-free survival was 12 months. The median response duration was 10 months. We conclude that metronomic chemotherapy can be used for patients with relapsed and or refractory DLBCL with reasonable outcome and acceptable toxicity. Standard approaches such as hematopoietic stem cell transplantation and chemo-immunotherapy combinations should be explored prior to a decision on metronomic chemotherapy.

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.

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.

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.

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

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.

Clinical features and relapse rates after surgery in type 1 autoimmune pancreatitis differ from type 2: a study of 114 surgically treated European patients.

PubMed

Detlefsen, Sönke; Zamboni, Giuseppe; Frulloni, Luca; Feyerabend, Bernd; Braun, Felix; Gerke, Oke; Schlitter, Anna Melissa; Esposito, Irene; Klöppel, Günter

2012-01-01

At the recent consensus conference on autoimmune pancreatitis (AIP) in Honolulu, we presented preliminary data from our study of surgically treated AIP patients. Our data strongly supported the separation of AIP into type 1 and type 2. Our study is based on a total of 114 surgically treated European AIP patients. Our aims were to elucidate serum IgG4 elevation, other organ involvement, relapse of disease, steroid treatment and diabetes after surgery in 114 surgically treated European AIP patients. 88 pancreaticoduodenectomies, 22 left-sided resections and 4 total pancreatectomies were examined. All cases were graded for granulocytic epithelial lesions, IgG4-positive cells, storiform fibrosis, phlebitis and eosinophilic granulocytes. Follow-up data were obtained from 102/114 patients, mean follow-up was 5.3 years. Histologically, 63 (55.3%) of the 114 patients fulfilled the criteria of type 1 AIP, while 51 (44.7%) patients fulfilled the criteria of type 2 AIP. Type 1 AIP patients were older and more often males than type 2 AIP patients. Elevation of serum IgG4, involvement of extrapancreatic organs, disease relapse, systemic steroid treatment and diabetes after surgery were noted more often in type 1 AIP, while inflammatory bowel disease (IBD) was observed mainly in type 2 AIP. Histological typing of AIP is clinically important because type 1 AIP is part of the IgG4-related disease and type 2 AIP is associated with IBD. Our data also show that relapse of disease and steroid treatment after surgery occur more frequently in type 1 than in type 2 AIP. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. 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

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.

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

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.

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.

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…

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

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

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.

Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

PubMed

Gunalp, Bengul; Okuyucu, Kursat; Ince, Semra; Ayan, Aslı; Alagoz, Engin

2017-01-01

There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients. Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.

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.

Mindfulness Based Relapse Prevention for Stimulant Dependent Adults: A Pilot Randomized Clinical Trial.

PubMed

Glasner-Edwards, Suzette; Mooney, Larissa J; Ang, Alfonso; Garneau, Hélène Chokron; Hartwell, Emily; Brecht, Mary-Lynn; Rawson, Richard A

2017-02-01

In light of the known associations between stress, negative affect, and relapse, mindfulness strategies hold promise as a means of reducing relapse susceptibility. In a pilot randomized clinical trial, we evaluated the effects of Mindfulness Based Relapse Prevention (MBRP), relative to a health education control condition (HE) among stimulant dependent adults receiving contingency management. All participants received a 12-week contingency management (CM) intervention. Following a 4-week CM-only lead in phase, participants were randomly assigned to concurrently receive MBRP (n=31) or HE (n=32). Stimulant dependent adults age 18 and over. A university based clinical research center. The primary outcomes were stimulant use, measured by urine drug screens weekly during the intervention and at 1-month post-treatment, negative affect, measured by the Beck Depression Inventory and Beck Anxiety Inventory, and psychiatric severity, measured by the Addiction Severity Index. Medium effect sizes favoring MBRP were observed for negative affect and overall psychiatric severity outcomes. Depression severity changed differentially over time as a function of group, with MBRP participants reporting greater reductions through follow-up (p=0.03; Effect Size=0.58). Likewise, the MBRP group evidenced greater declines in psychiatric severity, (p=0.01; Effect Size=0.61 at follow-up). Among those with depressive and anxiety disorders, MBRP was associated with lower odds of stimulant use relative to the control condition (Odds Ratio= 0.78, p=0.03 and OR=0.68, p=0.04). MBRP effectively reduces negative affect and psychiatric impairment, and is particularly effective in reducing stimulant use among stimulant dependent adults with mood and anxiety disorders.

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

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

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.

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.

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.

Preoperative lymphoscintigraphy and tumor histologic grade are associated with surgical detection of the sentinel lymph node.

PubMed

Arias Ortega, M; Torres Sousa, M Y; González García, B; Pardo García, R; González López, A; Delgado Portela, M

2014-01-01

To study which variables involved in the process of selective sentinel node biopsy (SSNB) influence the intraoperative detection of the sentinel lymph node. This was a prospective cross-sectional study in 210 patients (mean age, 54 years) diagnosed with breast cancer who underwent SSNB. We recorded clinical, radiological, radioisotope administration, surgical, and histological data as well as follow-up data. We did a descriptive analysis of the data and an associative analysis using multivariable regression. Deep injection alone was the most common route of radioisotope administration (72.7%). Most lesions were palpable (57.1%), presented as nodules (67.1%), measured less than 2 cm in diameter (64.8%), were located in the upper outer quadrant (49.1%), were ductal carcinomas (85.7%), were accompanied by infiltration (66.2%), and had a histologic grade of differentiation of ii (44.8%). Preoperative scintigraphy detected the sentinel node in 97.6% of cases and 95.7% were detected during the operation. One axillary relapse was observed. In the associative study, the variables "preoperative lymphoscintigraphy" and "histologic grade of differentiation of the tumor" were significantly associated with the detection of the sentinel lymph node during the operation. The probability of not detecting the sentinel lymph node during the surgical intervention is higher in patients with high histologic grade tumors or in patients in whom preoperative lymphoscintigraphy failed to detect the sentinel node. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas.

PubMed

Friedberg, Jonathan W; Mahadevan, Daruka; Cebula, Erin; Persky, Daniel; Lossos, Izidore; Agarwal, Amit B; Jung, Jungah; Burack, Richard; Zhou, Xiaofei; Leonard, E Jane; Fingert, Howard; Danaee, Hadi; Bernstein, Steven H

2014-01-01

Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas. Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles. We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event-related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response. The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated.

Phase II Study of Alisertib, a Selective Aurora A Kinase Inhibitor, in Relapsed and Refractory Aggressive B- and T-Cell Non-Hodgkin Lymphomas

PubMed Central

Friedberg, Jonathan W.; Mahadevan, Daruka; Cebula, Erin; Persky, Daniel; Lossos, Izidore; Agarwal, Amit B.; Jung, JungAh; Burack, Richard; Zhou, Xiaofei; Leonard, E. Jane; Fingert, Howard; Danaee, Hadi; Bernstein, Steven H.

2014-01-01

Purpose Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can correlate with more histologically aggressive forms of disease. We therefore designed a phase II study of alisertib, a selective AAK inhibitor, in patients with relapsed and refractory aggressive non-Hodgkin lymphomas. Patients and Methods Patients age ≥ 18 years were eligible if they had relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21-day cycles. Results We enrolled 48 patients. Histologies included DLBCL (n = 21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%), stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment-related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was 27%, including responses in three of 21 patients with DLBCL, three of 13 with MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib steady-state trough concentration (n = 25) revealed the expected pharmacokinetic variability, with a trend for higher incidence of adverse event–related dose reductions at higher trough concentrations. Analysis for AAK gene amplification and total AAK protein revealed no differences between histologies or correlation with clinical response. Conclusion The novel AAK inhibitor alisertib seems clinically active in both B- and T-cell aggressive lymphomas. On the basis of these results, confirmatory single-agent and combination studies have been initiated. PMID:24043741

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

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…

[Prodromal symptoms in schizophrenic relapse: A descriptive and comparative study].

PubMed

Bouhlel, S; Jones, Y; Khelifa, E; Msolly, M; Melki, W; El-Hechmi, Z

2012-10-01

Schizophrenia is a severe, chronic psychiatric disorder. After recovery from a first psychotic episode, 70% of patients have exacerbations. These exacerbations are preceded in 66 to 100% of cases by early signs. Prevention of relapses is the main object of dealing with schizophrenia. In fact, after a psychotic relapse, 17% of patients develop residual symptoms which did not exist before the relapse. Moreover, symptoms resistant to antipsychotics appear in 35% of patients after a relapse. Each relapse increases the risk of future relapses. Finally, the cost of treating patients with relapses is four times higher than in patients without relapses. Prevention of relapses is possible if we detect early signs. In fact, when specific interventions are applied in time, relapses can be avoided. Surprisingly, there is a scarcity of data on prodromal symptoms of schizophrenic relapses in the literature. In this study, we aimed to describe early signs of schizophrenic relapses, which are comparatively more frequent than those in stabilized outpatients. We conducted a retrospective, descriptive and comparative trial. We included 30 patients with schizophrenia who had recently experienced a psychotic relapse and a member of their families. We also included a control group of 30 stabilized outpatients with schizophrenia. All of the patients were diagnosed schizophrenic according to the DSM IV and had no secondary diagnosis. Only patients aged from 18 to 55 years and having an illness with an episodic evolution were included. The relapse group must have had a period off illness of more than one year and duration of the last remission greater than 3 months. We built a structured interview based on the data of the literature on early symptoms of relapses and on our clinical experience. It contained 93 items describing symptoms and feelings relevant to the period of relapse. The interview lasted about 1h. We collected demographic information from both groups. The relapse group was

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.

Isolated v-lesion in kidney transplant recipients: Characteristics, association with DSA, and histological follow-up.

PubMed

Rabant, Marion; Boullenger, Fanny; Gnemmi, Viviane; Pellé, Gaëlle; Glowacki, François; Hertig, Alexandre; Brocheriou, Isabelle; Suberbielle, Caroline; Taupin, Jean-Luc; Anglicheau, Dany; Legendre, Christophe; Duong Van Huyen, Jean-Paul; Buob, David

2018-04-01

Isolated v-lesion (IvL) represents a rare and challenging situation in renal allograft biopsies because it is unknown whether IvL truly represents rejection, antibody- or T cell-mediated, or not. This multicentric retrospective study describes the clinicopathological features of IvL with an emphasis on the donor-specific antibody (DSA) status, histological follow-up, and graft survival. Inclusion criteria were the presence of v-lesion with minimal interstitial (i ≤ 1) and microvascular inflammation (g + ptc≤1). C4d-positive biopsies were excluded. We retrospectively found 33 IvL biopsies in 33 patients, mainly performed in the early posttransplantation period (median time 27 days) and clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at the time of biopsy. IvL was treated by anti-rejection therapy in 21 cases (63.6%), whereas 12 (36.4%) were untreated. Seventy percent of untreated patients and 66% of treated patients showed favorable histological evolution on subsequent biopsy. Kidney graft survival in IvL was significantly higher than in a matched cohort of antibody-mediated rejection with arteritis. In conclusion, IvL is not primarily antibody-mediated and may show a favorable evolution. The heterogeneity of IvL pathophysiology on early biopsies should prompt DSA testing as well as close clinical and histological follow-up in all patients with IvL. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

PubMed

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

2013-12-01

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

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.

Immunohistochemical Expression of Ki67 and p53 in Wilms Tumor and Its Relationship with Tumor Histology and Stage at Presentation

PubMed Central

Krishna, O. H. Radhika; Kayla, Geetha; Abdul Aleem, Mohammed; Malleboyina, Ramani; Reddy Kota, Ramesh

2016-01-01

Aim. Evaluate tumor proliferation marker (Ki67) and p53 tumor suppressor marker in Wilms tumor and correlate with histology, anaplasia, and staging. Design. Prospective, hospital based study conducted at a tertiary pediatric referral centre in south India. Setting. Wilms tumor is the most common childhood renal malignancy worldwide. Anaplasia on histology is associated with treatment resistance but not with aggressiveness clinical presentation. Chemotherapy for Wilms tumor is based on histology and staging. Most patients respond to current chemotherapy protocol. However, a small fraction relapses or metastasizes. Affordable prognostic markers are needed for histopathological evaluation of this tumor. Subjects. Cases of histologically confirmed Wilms tumor over five years. Cases after chemotherapy were excluded as the immunostaining was inconsistent in necrotic areas. Methods. The clinical and radiological findings of 31 cases of Wilms tumor were documented at a tertiary pediatric referral hospital over five years. In addition to Hematoxylin and Eosin staining, Ki67 proliferation index and p53 expression were correlated with tumor histology and staging. Results. Age incidence was 3–8 years with female preponderance. Significant correlation was noted between Ki67 proliferation index and tumor staging. p53 expression was not useful in stratification of Wilms tumor. Conclusion. Ki67 was cost-effective immunohistochemical marker for prognostication of pediatric Wilms tumor. PMID:26904359

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.

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

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.

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.

Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

PubMed Central

Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

2015-01-01

Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

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

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.…

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.

Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.

PubMed

Benoit, Vivian M; Petrich, Annett; Alugupalli, Kishore R; Marty-Roix, Robin; Moter, Annette; Leong, John M; Boyartchuk, Victor L

2010-02-01

Host susceptibility to infection is controlled in large measure by the genetic makeup of the host. Spirochetes of the genus Borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing Lyme disease and relapsing fever. Relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. To facilitate studies of genetic control of susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes.

Ipilimumab for Patients with Relapse after Allogeneic Transplantation

PubMed Central

Davids, Matthew S.; Kim, Haesook T.; Bachireddy, Pavan; Costello, Caitlin; Liguori, Rebecca; Savell, Alexandra; Lukez, Alexander P.; Avigan, David; Chen, Yi-Bin; McSweeney, Peter; LeBoeuf, Nicole R.; Rooney, Michael S.; Bowden, Michaela; Zhou, Chensheng W.; Granter, Scott R.; Hornick, Jason L.; Rodig, Scott J.; Hirakawa, Masahiro; Severgnini, Mariano; Hodi, F. Stephen; Wu, Catherine J.; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Armand, Philippe; Streicher, Howard; Ball, Edward D.; Ritz, Jerome; Bashey, Asad; Soiffer, Robert J.

2016-01-01

BACKGROUND Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte–associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were

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

[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.

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.

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.

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)…

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…

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.

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…

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.

GRIZZLY/FAVOR Interface Project Report

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

Dickson, Terry L; Williams, Paul T; Yin, Shengjun

As part of the Light Water Reactor Sustainability (LWRS) Program, the objective of the GRIZZLY/FAVOR Interface project is to create the capability to apply GRIZZLY 3-D finite element (thermal and stress) analysis results as input to FAVOR probabilistic fracture mechanics (PFM) analyses. The one benefit of FAVOR to Grizzly is the PROBABILISTIC capability. This document describes the implementation of the GRIZZLY/FAVOR Interface, the preliminary verification and tests results and a user guide that provides detailed step-by-step instructions to run the program.

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.

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.

[Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].

PubMed

Klotz, L; Meuth, S G; Kieseier, B; Wiendl, H

2013-08-01

In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.

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

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

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.

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.

Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

PubMed Central

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

2017-01-01

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

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

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.

PubMed

Hauser, Stephen L; Bar-Or, Amit; Comi, Giancarlo; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Lublin, Fred; Montalban, Xavier; Rammohan, Kottil W; Selmaj, Krzysztof; Traboulsee, Anthony; Wolinsky, Jerry S; Arnold, Douglas L; Klingelschmitt, Gaelle; Masterman, Donna; Fontoura, Paulo; Belachew, Shibeshih; Chin, Peter; Mairon, Nicole; Garren, Hideki; Kappos, Ludwig

2017-01-19

B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate. The annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium-enhancing lesions per T 1 -weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta-1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta-1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion-related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta-1a. Neoplasms

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia: Efficacy and Tolerability

PubMed Central

Brown, Patrick; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul

2014-01-01

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials. PMID:24072240

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.

Active Learning: A Small Group Histology Laboratory Exercise in a Whole Class Setting Utilizing Virtual Slides and Peer Education

ERIC Educational Resources Information Center

Bloodgood, Robert A.

2012-01-01

Histology laboratory instruction is moving away from the sole use of the traditional combination of light microscopes and glass slides in favor of virtual microscopy and virtual slides. At the same time, medical curricula are changing so as to reduce scheduled time for basic science instruction as well as focusing on student-centered learning…

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

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.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

PubMed

Bohm, M; Jacobs, J W; Gupta, A; Gupta, S; Wo, J M

2017-01-01

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia

Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: the DEFINE study.

PubMed

Kappos, Ludwig; Gold, Ralf; Arnold, Douglas L; Bar-Or, Amit; Giovannoni, Gavin; Selmaj, Krzysztof; Sarda, Sujata P; Agarwal, Sonalee; Zhang, Annie; Sheikh, Sarah I; Seidman, Emily; Dawson, Katherine T

2014-02-01

Oral BG-12 (dimethyl fumarate), approved for the treatment of the relapsing forms of MS, has demonstrated clinical efficacy with an acceptable safety profile in the Phase III "Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (RRMS)" (DEFINE) and "Comparator and an Oral Fumarate in RRMS" (CONFIRM) studies. To evaluate the health-related quality of life (HRQoL) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study. Patients with RRMS were randomized to BG-12 240 mg twice (BID) or three times (TID) daily, or placebo, for 2 years. HRQoL was assessed by the Short Form-36 (SF-36), global assessment of well-being visual analog scale and the EuroQol-5D. In the 1237 patients from DEFINE, HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse. Change in SF-36 physical component summary scores during 2 years' treatment significantly favored BG-12 over placebo (both doses: p < 0.001). We saw similar benefits in other measures of functioning and general well-being as early as Week 24. These benefits were maintained during the study. Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures, which coupled with significant clinical efficacy, further support its use as a new treatment for RRMS.

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

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.

A Stochastic Polygons Model for Glandular Structures in Colon Histology Images.

PubMed

Sirinukunwattana, Korsuk; Snead, David R J; Rajpoot, Nasir M

2015-11-01

In this paper, we present a stochastic model for glandular structures in histology images of tissue slides stained with Hematoxylin and Eosin, choosing colon tissue as an example. The proposed Random Polygons Model (RPM) treats each glandular structure in an image as a polygon made of a random number of vertices, where the vertices represent approximate locations of epithelial nuclei. We formulate the RPM as a Bayesian inference problem by defining a prior for spatial connectivity and arrangement of neighboring epithelial nuclei and a likelihood for the presence of a glandular structure. The inference is made via a Reversible-Jump Markov chain Monte Carlo simulation. To the best of our knowledge, all existing published algorithms for gland segmentation are designed to mainly work on healthy samples, adenomas, and low grade adenocarcinomas. One of them has been demonstrated to work on intermediate grade adenocarcinomas at its best. Our experimental results show that the RPM yields favorable results, both quantitatively and qualitatively, for extraction of glandular structures in histology images of normal human colon tissues as well as benign and cancerous tissues, excluding undifferentiated carcinomas.

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.

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

PubMed

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p < .01). In addition, the low International Prognostic Index, low Prognostic Index for T cell lymphoma, or normal level of LDH in serum was associated with favorable prognosis. Grade 3/4 adverse effect was observed in 10 of 25 patients treated with GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL).

PubMed

Balzarotti, Monica; Brusamolino, Ercole; Angelucci, Emanuele; Carella, Angelo Michele; Vitolo, Umberto; Russo, Eleonora; Congiu, Angelagiovanna; Gotti, Manuel; Massidda, Stefania; Botto, Barbara; Annechini, Giorgia; Spina, Michele; Re, Alessandro; Zilioli, Vittorio Ruggero; Merli, Francesco; Salvi, Flavia; Stelitano, Caterina; Bonfichi, Maurizio; Rodari, Marcello; Murru, Roberta; Magagnoli, Massimo; Anastasia, Antonella; Mazza, Rita; Giordano, Laura; Santoro, Armando

2016-10-01

This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed.

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…

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.

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…

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.

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.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

PubMed

Battista, Marco Johannes; Cotarelo, Cristina; Jakobi, Sina; Steetskamp, Joscha; Makris, Georgios; Sicking, Isabel; Weyer, Veronika; Schmidt, Marcus

2014-07-01

The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients. Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM. The Kaplan-Meier method is used to estimate survival rates. Univariable Cox regression analysis showed that overexpression of EpCAM is associated with favorable prognosis in terms of progression-free survival (PFS) (p = 0.011) and disease-specific survival (DSS) (p = 0.003). In multivariable Cox regression analysis, overexpression of EpCAM retains its significance independent of established prognostic factors for longer PFS [hazard ratios (HR) 0.408, 95 % confidence interval (CI) 0.197-0.846, p = 0.003] but not for PFS (HR 0.666, 95 % CI 0.366-1.212, p = 0.183). Kaplan-Meier plots demonstrate an influence on 5-year PFS rates (0 vs. 27.6 %, p = 0.048) and DSS rates (11.8 vs. 54.0 %, p = 0.018). These findings support the hypothesis that the expression of EpCAM is associated with favorable prognosis in OC.

Time to Second-line Treatment and Subsequent Relative Survival in Older Patients With Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

PubMed

Ammann, Eric M; Shanafelt, Tait D; Larson, Melissa C; Wright, Kara B; McDowell, Bradley D; Link, Brian K; Chrischilles, Elizabeth A

2017-12-01

Novel targeted therapies offer excellent short-term outcomes in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL). However, there is disagreement over how widely these therapies should be used in place of standard chemo-immunotherapy (CIT). We investigated whether stratification on the length of the interval between first-line (T1) and second-line (T2) treatments could identify a subgroup of older patients with relapsed CLL/SLL with an expectation of normal overall survival, and for whom CIT could be an acceptable treatment choice. Patients with relapsed CLL/SLL who received T2 were identified from the SEER-Medicare Linked Database. Five-year relative survival (RS5; ie, the ratio of observed survival to expected survival based on population life tables) was assessed after stratifying patients on the interval between T1 and T2. We then validated our findings in the Mayo Clinic CLL Database. Among 1974 SEER-Medicare patients (median age = 77 years) who received T2 for relapsed CLL/SLL, longer time-to-retreatment was associated with a modestly improved prognosis (P = .01). However, even among those retreated ≥ 3 years after T1, survival was poor compared with the general population (RS5 = 0.50 or lower in SEER-Medicare). Similar patterns were observed in the younger Mayo validation cohort, although prognosis was better overall among the Mayo patients, and patients with favorable fluorescence in situ hybridization retreated ≥ 3 years after T1 had close to normal expected survival (RS5 = 0.87). Further research is needed to quantify the degree to which targeted therapies provide meaningful improvements over CIT in long-term outcomes for older patients with relapsed CLL/SLL. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

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.

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

PubMed

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

2008-10-01

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

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.

Phase I study of bortezomib in combination with irinotecan in patients with relapsed/refractory high-risk neuroblastoma.

PubMed

Mody, Rajen; Zhao, Lili; Yanik, Gregory Anthony; Opipari, Valerie

2017-11-01

Prognosis for relapsed/refractory high-risk neuroblastoma (HR-NBL) remains poor. Bortezomib, a proteasome inhibitor, has shown preclinical activity against NBL as a single agent and in combination with cytotoxic chemotherapy including irinotecan. Eighteen HR-NBL patients with primary refractory (n = 8) or relapsed (n = 10) disease were enrolled in a Phase I study using modified Time To Event Continual Reassessment Method. Bortezomib (1.2 mg/m 2 /day) was administered on days 1, 4, 8, and 11 intravenously (IV) and irinotecan was given IV on days 1-5 (35, 40, or 45 mg/m 2 /day, on dose levels [DL] 1-3, respectively). The maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and response rate were examined. Eighteen NBL patients were evaluable for toxicity; 17 were evaluable for response assessment. A total of 142 courses were delivered (mean 8.2, median 2, range 1-48), with two patients receiving more than 40 courses of therapy. Two DLTs were reported, including a grade 4 thrombocytopenia (DL2) and a grade 3 irritability (DL3). MTD was estimated as DL3. Two of 17 (12%) evaluable patients showed objective responses (ORs) lasting more than 40 courses, including 1 partial remission and 1 complete remission. Four patients (23%) had prolonged stable disease (SD) lasting six or more courses, with a total of 35% study patients demonstrating clinical benefit in the form of prolonged OR or SD. The combination of bortezomib and irinotecan was well tolerated by patients with relapsed/refractory NBL with favorable toxicity profile. It also showed modest but promising clinical activity and merits further testing in Phase II studies. © 2017 Wiley Periodicals, Inc.

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.

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

A simple risk scoring system for prediction of relapse after inpatient alcohol treatment.

PubMed

Pedersen, Mads Uffe; Hesse, Morten

2009-01-01

Predicting relapse after alcoholism treatment can be useful in targeting patients for aftercare services. However, a valid and practical instrument for predicting relapse risk does not exist. Based on a prospective study of alcoholism treatment, we developed the Risk of Alcoholic Relapse Scale (RARS) using items taken from the Addiction Severity Index and some basic demographic information. The RARS was cross-validated using two non-overlapping samples, and tested for its ability to predict relapse across different models of treatment. The RARS predicted relapse to drinking within 6 months after alcoholism treatment in both the original and the validation sample, and in a second validation sample it predicted admission to new treatment 3 years after treatment. The RARS can identify patients at high risk of relapse who need extra aftercare and support after treatment.

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…

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

Histological Effects of Enamel Matrix Derivative on Exposed Dental Pulp.

PubMed

Bajić, Marijana Popović; Danilović, Vesna; Prokić, Branislav; Prokić, Bogomir Bolka; Manojlović, Milica; Živković, Slavoljub

2015-01-01

Direct pulp capping procedure is a therapeutic application of a drug on exposed tooth pulp in order to ensure the closure of the pulp chamber and to allow the healing process to take place. The aim of this study was to examine the histological effects of Emdogain® on exposed tooth pulp of a Vietnamese pig (Sus scrofa verus). The study comprised 20 teeth of a Vietnamese pig. After class V preparation on the buccal surfaces of incisors, canines and first premolars, pulp was exposed. In the experimental group, the perforations were capped with Emdogain® (Straumann, Basel, Switzerland), while in the control group pulp capping was performed with MTA® (Dentsply Tulsa Dental, Johnson City, TN, USA). All cavities were restored with glass-ionomer cement (GC Fuji VIII, GC Corporation, Tokyo, Japan). The observational period was 28 days, after which the animal was sacrificed and histological preparations were made. A light microscope was used to analyze dentin bridge formation, tissue reorganization and inflammation, and the presence of bacteria in the pulp. The formation of dentin bridge was observed in the experimental and control groups. Inflammation of the pulp was mild to moderate in both groups. Angiogenesis and many odontoblast-like cells, responsible for dentin bridge formation, were observed. Necrosis was not observed in any case, nor were bacteria present in the pulp. Histological analysis indicated a favorable therapeutic effect of Emdogain® Gel in direct pulp capping of Vietnamese pigs. Pulp reaction was similar to that of MTA®.

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

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.

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.

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

PubMed

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

2015-09-01

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

New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images.

PubMed

Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K; Schad, Lothar R; Zöllner, Frank Gerrit

2015-01-01

Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin-3,3'-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics.

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

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

[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.

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.

[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.

Salaries in histology.

PubMed

Buesa, René J

2008-04-01

An analysis of histology salaries from the last 4 national surveys conducted by the American Society of Clinical Pathologists is presented. The regional variations within and between years for histology salaries presented in the last 4 national surveys of medical laboratory specialties are not statistically significant. Local variations greater than the national variations reflect the preponderant effect of local supply and demand over regional characteristics. Salaries by hospitals are significantly different only between 2 size categories and the supervisors' salary. There is no correlation between the salary increase for any histology position in any one year and the vacancy level in the previous year. On the other hand, the correlation between histotechnicians' salaries and both the cost of living and the median income are significant, as well as between the latter and the supervisors' salary. The histotechnologists' salaries are significantly correlated with the consumer price index but not with the inflation rate. A survey of histology salaries in foreign countries was also undertaken and compared with salaries in the United States. National salaries rank close to the general average for 10 foreign countries when expressed as ratios with the personal gross domestic product or with the countries' minimum wage. For the midpoint salary ranges, the United States ranks fourth after Canada, the United Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted to local costs of living in contrast with United States' salary characteristics. Histology salaries rest on negotiations within each employer's salary structure and fluctuate according to license level, documented studies, special training(s), years of experience, references, and the ability to negotiate, where each side tries to take advantage of the other. The result is a heterogeneous and chaotic salary situation driven by personal and local needs, where the histology worker usually

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...

New Colors for Histology: Optimized Bivariate Color Maps Increase Perceptual Contrast in Histological Images

PubMed Central

Kather, Jakob Nikolas; Weis, Cleo-Aron; Marx, Alexander; Schuster, Alexander K.; Schad, Lothar R.; Zöllner, Frank Gerrit

2015-01-01

Background Accurate evaluation of immunostained histological images is required for reproducible research in many different areas and forms the basis of many clinical decisions. The quality and efficiency of histopathological evaluation is limited by the information content of a histological image, which is primarily encoded as perceivable contrast differences between objects in the image. However, the colors of chromogen and counterstain used for histological samples are not always optimally distinguishable, even under optimal conditions. Methods and Results In this study, we present a method to extract the bivariate color map inherent in a given histological image and to retrospectively optimize this color map. We use a novel, unsupervised approach based on color deconvolution and principal component analysis to show that the commonly used blue and brown color hues in Hematoxylin—3,3’-Diaminobenzidine (DAB) images are poorly suited for human observers. We then demonstrate that it is possible to construct improved color maps according to objective criteria and that these color maps can be used to digitally re-stain histological images. Validation To validate whether this procedure improves distinguishability of objects and background in histological images, we re-stain phantom images and N = 596 large histological images of immunostained samples of human solid tumors. We show that perceptual contrast is improved by a factor of 2.56 in phantom images and up to a factor of 2.17 in sets of histological tumor images. Context Thus, we provide an objective and reliable approach to measure object distinguishability in a given histological image and to maximize visual information available to a human observer. This method could easily be incorporated in digital pathology image viewing systems to improve accuracy and efficiency in research and diagnostics. PMID:26717571

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.

Protective Effects on Central Nervous System by Acidic Polysaccharide of Panax ginseng in Relapse-Remitting Experimental Autoimmune Encephalomyelitis-Induced SJL/J Mice.

PubMed

Bing, So Jin; Ha, Danbee; Hwang, Insun; Park, Eunjin; Ahn, Ginnae; Song, Jie-Young; Jee, Youngheun

2016-01-01

Bearing pathologic and clinical similarities to human multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) is used as a murine model to test potential therapeutic agents for MS. Recently, we reported the protective effects of an acidic polysaccharide of Panax ginseng (APG) in C57BL/6 strain-dependent EAE, a model of primary progressive MS. In this study, we extend our previous findings on the therapeutic capacity of APG in relapsing-remitting EAE (rr-EAE), the animal model to closely mimic recurrent inflammatory demyelination lesions of relapsing-remitting MS. Treatments with APG led to a significant reduction of clinical symptoms and the relapse rate of EAE than vehicle treatments. Consistent with this, histological examination revealed that APG markedly modulated the infiltration of CD4[Formula: see text] T cells and CD11b[Formula: see text] macrophages into the spinal cord and the APG-treated CNS was devoid of demyelination and axonal damages. In addition, APG decreased the proliferation of peripheral PLP-reactive T cells and the production of pro-inflammatory factors such as IFN-[Formula: see text], IL-17 and TNF-[Formula: see text]. The fact that APG can induce clinically beneficial effects to distinct types of EAE furthers our understanding on the basis of its immunosuppression in EAE and, possibly, in MS. Our results suggest that APG may serve as a new therapeutic agent for MS as well as other human autoimmune diseases, and warrants continued evaluation for its translation into therapeutic application.

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.

Substance Abuse, Relapse, and Treatment Program Evaluation in Malaysia: Perspective of Rehab Patients and Staff Using the Mixed Method Approach

PubMed Central

Chie, Qiu Ting; Tam, Cai Lian; Bonn, Gregory; Dang, Hoang Minh; Khairuddin, Rozainee

2016-01-01

This study examined reasons for substance abuse and evaluated the effectiveness of substance treatment programs in Malaysia through interviews with rehab patients and staff. Substance rehab patients (aged 18–69 years; n = 30) and staff (ages 30–72 years; n = 10) participated in semi-structured interviews covering a range of topics, including family and peer relationships, substance use and treatment history, factors for substance use and relapse, motivation for entering treatment, work experience, job satisfaction, treatment evaluation, and patient satisfaction. Most patients did not demonstrate the substance progression trend and had normal family relationships. Most patients reported having peers from normal family backgrounds as well. Various environmental and personal factors was cited as contributing to substance abuse and relapse. There was no significant difference between patient and staff program evaluation scores although the mean score for patients was lower. A holistic treatment approach with a combination of cognitive–behavioral, medical, social, and spiritual components was favored by patients. Suggestions for improving existing programs include better tailoring treatment to individual needs, and providing more post-treatment group support. PMID:27303313

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

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.

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.

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.

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

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…

Utility of bortezomib retreatment in relapsed or refractory multiple myeloma patients: a multicenter case series.

PubMed

Wolf, Jeffrey; Richardson, Paul G; Schuster, Michael; LeBlanc, Annette; Walters, Ian B; Battleman, David S

2008-10-01

Bortezomib therapy has become an important part of the standard of care for patients with relapsed multiple myeloma, and preliminary clinical evidence suggests that bortezomib retreatment in patients previously treated with the drug may prolong disease control. This retrospective study was designed to clarify the utility of bortezomib as a repeat therapy. We reviewed records from 3 major cancer centers that had participated in the phase II (SUMMIT or CREST) or phase III (APEX) registration studies to identify patients who were subsequently retreated off protocol with bortezomib-based therapy. We found 22 patients who received bortezomib retreatment following a 60 or more day gap between bortezomib treatments. Twelve patients had intervening therapy between initial bortezomib treatment and bortezomib retreatment. During retreatment, 14 of 22 patients received bortezomib in combination with another antineoplastic agent. The overall response rate for bortezomib retreatment was 50% (9% complete responses). The median length of retreatment was 5.1 months in responding patients and 2.4 months in nonresponding patients. Therapy was terminated due to unmanageable toxicity in 2 patients during retreatment, compared with 6 patients during initial treatment. During retreatment, no patients required dose reduction due to peripheral neuropathy, compared to 4 patients during their initial treatment. Thus, bortezomib retreatment appears to be safe and effective. Favorable observed response rates with bortezomib retreatment suggest that it may be a viable option for relapsed or refractory multiple myeloma, even in patients previously exposed to bortezomib.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in second remission or relapse.

PubMed

Lin, K H; Jou, S T; Chen, R L; Lin, D T; Lui, L T; Lin, K S

1994-01-01

Most children with acute lymphoblastic leukemia (ALL) are successfully treated by chemotherapy. For those patients, who relapse on therapy, bone marrow transplantation (BMT) is considered most appropriate after a subsequent remission is achieved. Three boys with ALL aged from 9 to 13 years met these criteria and received BMT from their HLA-compatible sisters after marrow ablation with total body irradiation 12 Gy plus high dose cytosine arabinoside 3 gm/m2/12h x 12 doses and graft-versus-host disease (GVHD) prophylaxis with cyclosporine plus short course methotrexate from March 10, 1989 to May 23, 1992. Filgrastim (rhG-CSF) was used to hasten the recovery of granulocyte in one patient. All three patients got full engraftment and two had grade 1 acute GVHD. None of them developed chronic GVHD. Two patients have disease-free survival over 51 and 12 months respectively post BMT without further chemotherapy. One patient died of recurrent refractory leukemia 5 months after BMT. The toxicity of this conditioning regimen included photophobia, conjunctivitis and erythematous skin rashes. One patient who received filgrastim from day 1 to 21 developed severe bone pain. However, this patient had faster recovery of granulocyte count than the other two patients. The preliminary results of this work favors BMT for children with recurrent ALL whose ultimate survival is usually poor when treated with chemotherapy. Further efforts are necessary to investigate new methods for reducing leukemic relapse in ALL patients undergoing BMT.

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…

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.

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.

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

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

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.

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

43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

Clinico-Histologic Conferences: Histology and Disease

ERIC Educational Resources Information Center

Shaw, Phyllis A.; Friedman, Erica S.

2012-01-01

Providing a context for learning information and requiring learners to teach specific content has been demonstrated to enhance knowledge retention. To enhance students' appreciation of the role of science and specifically histology in clinical reasoning, disease diagnosis, and treatment, a new teaching format was created to provide clinical…

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

PubMed Central

Kawedia, Jitesh D.; Liu, Chengcheng; Pei, Deqing; Cheng, Cheng; Fernandez, Christian A.; Howard, Scott C.; Campana, Dario; Panetta, John C.; Bowman, W. Paul; Evans, William E.; Pui, Ching-Hon

2012-01-01

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse. PMID:22117041

Efficacy of levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome.

PubMed

Ekambaram, Sudha; Mahalingam, Vijayakumar; Nageswaran, Prahlad; Udani, Amish; Geminiganesan, Sangeetha; Priyadarshini, Shweta

2014-05-01

To assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome. Retrospective analysis of hospital case records. Pediatric nephrology department of a tertiary referral pediatric hospital. 62 children with frequently relapsing nephrotic syndrome and 35 children with steroid-dependent nephrotic syndrome. Case records of children who were diagnosed as steroid-dependant or frequently-relapsing nephrotic syndrome from June 2004 to June 2011, were reviewed. Levamisole was given daily (2 mg/kg/d) along with tapering doses of alternate day steroids after remission on daily steroids. Levamisole was effective in 77.3% children with a better (80.6%) efficacy in frequently relapsing nephrotic syndrome. A total of 34 children completed 1 year follow-up post levamisole therapy. The cumulative mean (SD) steroid dose 1-year before therapy was 4109(1154) mg/m2 and 1-year post therapy was 661 (11) mg/m2 (P<0.001). The relapses were also less during the period of post-levamisole therapy. Levamisole is an effective alternative therapy in frequently relapsing and steroid-dependent nephrotic syndrome.

Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

PubMed

Bhagirath, Vinai C; Kelton, John G; Moore, Jane; Arnold, Donald M

2012-12-01

Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain. We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months. During her latest TTP relapse, multiple treatments were administered including rituximab retreatment. After the first dose (375 mg/m2), she developed serum sickness requiring further doses to be deferred. Three subsequent doses were administered at 4-month intervals over the course of 12 months. ADAMTS13 activity was measured by von Willebrand factor (VWF) digestion. ADAMTS13 inhibition was measured by a modification of the VWF digestion assay and anti-ADAMTS13 antibodies were measured by enzyme-linked immunoassay (enzyme-linked immunosorbent assay, American Diagnostica). Clinical and laboratory remission were achieved after one dose of rituximab, with normalization of ADAMTS13 activity and disappearance of ADAMTS13 inhibitor. Three subsequent doses of rituximab were given without incident and the patient remained in remission after 3.5 years of follow-up (2.5 years since her last dose of rituximab). Maintenance dosing of rituximab should be considered in some patients with relapsing TTP. © 2012 American Association of Blood Banks.

Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

ERIC Educational Resources Information Center

Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

2012-01-01

This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…

Factors associated with relapse after a response to electroconvulsive therapy in unipolar versus bipolar depression.

PubMed

Itagaki, Kei; Takebayashi, Minoru; Shibasaki, Chiyo; Kajitani, Naoto; Abe, Hiromi; Okada-Tsuchioka, Mami; Yamawaki, Shigeto

2017-01-15

While electroconvulsive therapy (ECT) treatment for depression is highly effective, the high rate of relapse is a critical problem. The current study investigated factors associated with the risk of relapse in mood disorders in patients in which ECT was initially effective. The records of 100 patients with mood disorders (61 unipolar depression, 39 bipolar depression) who received and responded to an acute ECT course were retrospectively reviewed. Associations between clinical variables and relapse after responding to acute ECT were analyzed. The Ethics Committee of NHO Kure Medical Center approved the study protocol. After one year, the percentage of relapse-free patients was 48.7%. There was no significant difference between patients with either unipolar or bipolar depression who were relapse-free (unipolar: 51.1%, bipolar: 45.5%, P=0.603). Valproate maintenance pharmacotherapy in unipolar depression patients was associated with a lower risk of relapse compared to patients without valproate treatment (multivariate analysis, hazard ratio: 0.091; P=0.022). Lithium treatment, reportedly effective for unipolar depression following a course of ECT, tended to lower the risk of relapse (hazard ratio: 0.378; P=0.060). For bipolar depression, no treatment significantly reduced the risk of relapse. The current findings were retrospective and based on a limited sample size. The relapse-free rate was similar between unipolar and bipolar depression. Valproate could have potential for unipolar depression patients as a maintenance therapeutic in preventing relapse after ECT. Copyright © 2016 Elsevier B.V. All rights reserved.

Tick-Borne Relapsing Fever Spirochetes in the Americas

PubMed Central

Lopez, Job E.; Krishnavahjala, Aparna; Garcia, Melissa N.; Bermudez, Sergio

2016-01-01

Relapsing fever spirochetes are tick- and louse-borne pathogens that primarily afflict those in impoverished countries. Historically the pathogens have had a significant impact on public health, yet currently they are often overlooked because of the nonspecific display of disease. In this review, we discuss aspects of relapsing fever (RF) spirochete pathogenesis including the: (1) clinical manifestation of disease; (2) ability to diagnose pathogen exposure; (3) the pathogen’s life cycle in the tick and mammal; and (4) ecological factors contributing to the maintenance of RF spirochetes in nature. PMID:28959690

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.

[Relapse prevention program consisting of coping skills training, cue exposure treatment, and letter therapy for Japanese alcoholic men who relapsed after standard cognitive-behavioral therapy].

PubMed

Yokoyama, Akira; Matsushita, Sachio; Toyama, Tomomi; Nakayama, Hideki; Takimura, Tsuyoshi; Kimura, Mitsuru; Yoneda, Junichi; Maesato, Hitoshi; Mizukami, Takeshi; Higuchi, Susumu; Yokoyama, Tetsuji

2015-04-01

Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention

Primaquine treatment and relapse in Plasmodium vivax malaria

PubMed Central

2016-01-01

The relapsing peculiarity of Plasmodium vivax is one of the prime reasons for sustained global malaria transmission. Global containment of P. vivax is more challenging and crucial compared to other species for achieving total malaria control/elimination. Primaquine (PQ) failure and P. vivax relapse is a major global public health concern. Identification and characterization of different relapse strains of P. vivax prevalent across the globe should be one of the thrust areas in malaria research. Despite renewed and rising global concern by researchers on this once ‘neglected’ species, research and development on the very topic of P. vivax reappearance remains inadequate. Many malaria endemic countries have not mandated routine glucose-6-phosphate dehydrogenase (G6PD) testing before initiating PQ radical cure in P. vivax malaria. This results in either no PQ prescription or thoughtless prescription and administration of PQ to P. vivax patients by healthcare providers without being concerned about patients’ G6PD status and associated complications. It is imperative to ascertain the G6PD status and optimum dissemination of PQ radical cure in all cases of P. vivax malaria across the globe. There persists a compelling need to develop/validate a rapid, easy-to-perform, easy-to-interpret, quality controllable, robust, and cost-effective G6PD assay. High-dose PQ of both standard and short duration appears to be safe and more effective for preventing relapses and should be practiced among patients with normal G6PD activity. Multicentric studies involving adequately representative populations across the globe with reference PQ dose must be carried out to determine the true distribution of PQ failure. Study proving role of cytochrome P450-2D6 gene in PQ metabolism and association of CYP2D6 metabolizer phenotypes and P. vivax relapse is of prime importance and should be carried forward in multicentric systems across the globe. PMID:27077309

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

PubMed

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-07-01

Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

SOX9 expression predicts relapse of stage II colon cancer patients.

PubMed

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

2016-06-01

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

Association between methylenetetrahydrofolate reductase polymorphisms and the relapse of acute lymphoblastic leukemia: a meta-analysis.

PubMed

He, H-R; Chen, S-Y; You, H-S; Hu, S-S; Sun, J-Y; Dong, Y-L; Lu, J

2014-10-01

Relapse is a threat in patients treated for acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) activity may affect the sensitivity of patients to folate-based chemotherapeutic drugs, thus influencing the relapse risk. Two polymorphisms of the gene encoding MTHFR, C677T and A1298C, alter MTHFR enzyme activity and may be associated with ALL relapse. The aim of this meta-analysis was to clarify the correlation between the C677T and A1298C polymorphisms and ALL relapse. To this end, data were collected from studies of the association between these two polymorphisms and ALL relapse. Analysis of the data revealed a serious contradiction among the results. A recessive model demonstrated that the ALL relapse risk was significantly increased in carriers of the 677 TT genotype, especially for pediatric ALL, but was unaffected by the A1298C polymorphism. These findings confirm that the MTHFR C677T polymorphism could be considered as a good marker of the pediatric ALL relapse risk.

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

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.

Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)

ClinicalTrials.gov

2017-12-04

Hematologic Cancer; Relapse Leukemia; Relapsed Adult ALL; Relapsed Adult AML; Relapsed CLL; Relapsed Non Hodgkin Lymphoma; Relapsed Hodgkin's Lymphoma; Relapsed Myelodysplastic Syndromes; Relapsed Multiple Myeloma

[Central nervous system relapse in diffuse large B cell lymphoma: Risk factors].

PubMed

Sancho, Juan-Manuel; Ribera, Josep-Maria

2016-01-15

Central nervous system (CNS) involvement by lymphoma is a complication associated, almost invariably, with a poor prognosis. The knowledge of the risk factors for CNS relapse is important to determine which patients could benefit from prophylaxis. Thus, patients with very aggressive lymphomas (such as lymphoblastic lymphoma or Burkitt's lymphoma) must systematically receive CNS prophylaxis due to a high CNS relapse rate (25-30%), while in patients with indolent lymphoma (such as follicular lymphoma or marginal lymphoma) prophylaxis is unnecessary. However, the question about CNS prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, remains controversial. The information available is extensive, mainly based on retrospective and heterogeneous studies. There seems that immunochemotherapy based on rituximab reduces the CNS relapse rate. On the other hand, patients with increased serum lactate dehydrogenase plus more than one extranodal involvement seem to have a higher risk of CNS relapse, but a prophylaxis strategy based only on the presence of these 2 factors does not prevent all CNS relapses. Patients with involvement of testes or breast have high risk of CNS relapse and prophylaxis is mandatory. Finally, CNS prophylaxis could be considered in patients with DLBCL and renal or epidural space involvement, as well as in those cases with MYC rearrangements, although additional studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Cocaine influences alcohol-seeking behavior and relapse drinking in alcohol-preferring (P) rats.

PubMed

Hauser, Sheketha R; Wilden, Jessica A; Deehan, Gerald A; McBride, William J; Rodd, Zachary A

2014-10-01

The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse. Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect. Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline. The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay). Copyright © 2014 by the Research Society on Alcoholism.

[Clinical and microbiological profile of patients experiencing relapses of tuberculosis in Tunisia].

PubMed

Mjid, M; Hedhli, A; Zakhma, M; Zribi, M; Ouahchi, Y; Toujani, S; Cherif, J

2018-04-01

Relapse of tuberculosis (TB) is known to be as one of the major risk factors for resistant TB. The aim of this study is to focus on clinical, radiological and bacteriological features of patients with pulmonary TB relapse. We performed a retrospective survey in the respiratory department of the teaching hospital La Rabta in Tunis between January 2000 and December 2014. Data of patients with a pulmonary TB relapse were analyzed. During the study period, among 1250 patients hospitalized for pulmonary TB, 44 had a TB relapse. The TB relapse rate was estimated to be at 3.5%. The average age was 43.95±16.7 years. Sex ratio was 5,2. Eighty one percent of patients were current smokers. Alcoholism was found in 40.9% of cases. The mean time to relapse was 6.37±3.7 years. The radiological lesions were moderately extended at least in 54.6% of cases. A resistant TB was found in 33% of cases (mono-resistance: 33.3%, multi-drug resistance (TB-MR): 11,1%, poly-resistance: 55.5%). The most incriminated drugs were isoniazid, rifampicin and pyrazinamide. One patient received TB-MR treatment regimen for 18 months. In the other cases, the duration of treatment was prolonged. Recovery was obtained in 72.7% of cases, two patients died and 22.7% of patients were lost to follow up. In Tunisia, TB relapse usually affects young male patients who are often alcoholic and smokers. Resistant TB is frequent among these patients. These findings lead us to emphasize the need of rapid diagnosis tools and adapted treatment regimen in these patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review].

PubMed

Zuo, Yingxi; Wang, Jingbo; Lu, Aidong; Jia, Yueping; Wu, Jun; Dong, Lujia; Chang, Lungji; Zhang, Leping

2016-02-01

To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL). A relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed. An 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion. Treatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis.

PubMed

Chiao, Evelyn; Meyer, Kellie

2009-06-01

Disease-modifying therapy (DMT) is the largest single-cost item that contributes to the total per-patient cost of multiple sclerosis (MS), a disabling disorder of the central nervous system. Natalizumab is the most recent DMT to be approved for the treatment of relapsing MS and may be an attractive alternative to interferon beta and glatiramer acetate (GA). To determine from the perspective of a United States payer (1) the incremental cost effectiveness of natalizumab compared with other DMTs and (2) the budgetary impact of utilization of natalizumab for the treatment of relapsing MS. A combined cost effectiveness and budget impact model was developed. Model inputs were drug acquisition costs (wholesale acquisition cost), costs of drug administration and monitoring, costs of treating relapses, anticipated reduction in relapse rates after 2 years of therapy, and estimated market utilization of natalizumab. Outcomes included total 2-year costs of therapy per patient, costs per relapse avoided for each treatment, and overall 2-year costs to the health plan and per member per month (PMPM) costs. Drug acquisition costs are in 2008 US dollars, and all other costs were inflated to 2008 US dollars when necessary. Univariate sensitivity analyses were performed to determine the model inputs with the greatest influence on the cost per relapse avoided for natalizumab. The overall 2-year cost of therapy per patient was $72,120 for natalizumab, $56,790 for intramuscular (IM) interferon beta-1a (IFNbeta-1a), $56,773 for IFNbeta-1b, $57,180 for GA, and $58,538 for subcutaneous (SC) IFNbeta-1a. The cost per relapse avoided was lowest for natalizumab at $56,594, followed by $87,791 for IFNbeta-1b, $93,306 for IM IFNbeta-1a, $96,178 for SC IFNbeta-1a, and $103,665 for GA. The incremental cost-effectiveness ratios of natalizumab relative to IM IFNbeta-1a, IFNbeta-1b, GA, and SC IFNbeta-1a were $23,029, $24,452, $20,671, and $20,403 per additional relapse avoided, respectively. An

Genomic Analyses Reveal the Common Occurrence and Complexity of Plasmodium vivax Relapses in Cambodia

PubMed Central

Popovici, Jean; Friedrich, Lindsey R.; Kim, Saorin; Bin, Sophalai; Run, Vorleak; Lek, Dysoley

2018-01-01

ABSTRACT Plasmodium vivax parasites have a unique dormant stage that can cause relapses weeks or months after the initial infection. These dormant parasites are among the main challenges of vivax malaria control as they constitute a reservoir that is difficult to eliminate. Since field studies are confounded by reinfections and possible recrudescence of drug-resistant parasites, most analyses of P. vivax relapses have focused on travelers returning from regions of malaria endemicity. However, it is not clear whether these individuals accurately recapitulate the relapse patterns of repeatedly infected individuals residing in areas of endemicity. Here, we present analyses of vivax malaria patients enrolled in a tightly controlled field study in Cambodia. After antimalarial drug treatment was administered, we relocated 20 individuals to a nontransmission area and followed them for 60 days, with blood collection performed every second day. Our analyses reveal that 60% of the patients relapsed during the monitoring period. Using whole-genome sequencing and high-throughput genotyping, we showed that relapses in Cambodia are often polyclonal and that the relapsing parasites harbor various degrees of relatedness to the parasites present in the initial infection. Our analyses also showed that clone populations differed dynamically, with new clones emerging during the course of the relapsing infections. Overall, our study data show that it is possible to investigate the patterns, dynamics, and diversity of P. vivax relapses of individuals living in a region of malaria endemicity and reveal that P. vivax relapses are much more pervasive and complex than previously considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02118090.) PMID:29362233

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

Persistent monoclonality after histological remission in gastric mucosa-associated lymphoid tissue lymphoma treated with chemotherapy and/or surgery: influence of t(11;18)(q21;q21).

PubMed

Santón, Almudena; García-Cosio, Mónica; Bellosillo, Beatriz; Rodríguez, Patricia; Cristóbal, Eva; Serrano, Sergio; Besses, Carlos; Abraira, Victor; Salar, Antonio; Montalbán, Carlos

2008-08-01

The purpose of this work was to study retrospectively the molecular response and outcome of 19 gastric mucosa associated lymphoid tissue (MALT) lymphoma patients achieving histological remission after chemotherapy or surgery. Immunoglobulin heavy chain variable (IgV(H)) gene rearrangements were studied by PCR in biopsies obtained at diagnosis and follow-up. Presence of t(11;18)(q21;q21) was studied by FISH or RT-PCR. Sequencing analysis of three t(11;18)(q21;q21) positive and two negative lymphomas with persistent monoclonal IgV(H) rearrangements was also performed. Long-term IgV(H) monoclonality was demonstrated in 11/19 patients (58%); in five of them monoclonal rearrangements were present in all samples throughout the follow-up. Persistent IgV(H) monoclonality was detected a median of 49 months after the achievement of histological response and did not condition histological relapse in most cases. All three t(11;18)(q21;q21) positive patients had maintained IgV(H) monoclonality and sequencing analyses revealed the same mutated IgV(H) alleles in the diagnostic and the follow-up samples. Over half of the patients with gastric MALT lymphoma with histological response after chemotherapy and/or surgery have long-term persistent monoclonality. The presence of t(11;18)(q21;q21) seems to condition long-term persistence of the initial lymphoma clone.trade mark.

PDL Progenitor-Mediated PDL Recovery Contributes to Orthodontic Relapse.

PubMed

Feng, L; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; He, D; Gan, Y; Kou, X; Zhou, Y

2016-08-01

Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem /: progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90(+) PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal-induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor-β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90(+) PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling. © International & American Associations for Dental Research 2016.

3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

PubMed Central

Gibson, Eli; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Pautler, Stephen; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

2013-01-01

Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9° (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be

Injury and subsequent regeneration of muscles for activation of local innate immunity to facilitate the development and relapse of autoimmune myositis in C57BL/6 mice.

PubMed

Kimura, Naoki; Hirata, Shinya; Miyasaka, Nobuyuki; Kawahata, Kimito; Kohsaka, Hitoshi

2015-04-01

To determine whether injury and regeneration of the skeletal muscles induce an inflammatory milieu that facilitates the development and relapse of autoimmune myositis. The quadriceps of C57BL/6 mice were injured with bupivacaine hydrochloride (BPVC) and evaluated histologically. Macrophages and regenerating myofibers in the treated muscles and differentiating C2C12 myotubes were examined for cytokine expression. Mice were immunized with C protein fragments at the base of the tail and in the right hind footpads (day 0) to evoke systemic anti-C protein immunity and to induce local myositis in the right hind limbs. The contralateral quadriceps muscles were injured with BPVC or phosphate buffered saline (PBS) on day 7 or after spontaneous regression of myositis (day 42). The quadriceps muscle in nonimmunized mice was injured with BPVC on day 7. The muscles were examined histologically 14 days after treatment. The BPVC-injured muscles had macrophage infiltration most abundantly at 3 days after the injection, with emergence of regenerating fibers from day 5. The macrophages expressed inflammatory cytokines, including tumor necrosis factor α, interleukin-1β, and CCL2. Regenerating myofibers and C2C12 myotubes also expressed the cytokines. The BPVC-injected muscles from nonimmunized mice had regenerating myofibers with resolved cell infiltration 14 days after treatment. In mice preimmunized with C protein fragments, the muscles injected with BPVC on day 7 as well as on day 42, but not those injected with PBS, had myositis accompanied by CD8+ T cell infiltration. Injury and regeneration could set up an inflammatory milieu in the muscles and facilitate the development and relapse of autoimmune myositis. Copyright © 2015 by the American College of Rheumatology.

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.

Comparable post-relapse outcomes between haploidentical and matched related donor allogeneic stem cell transplantation.

PubMed

Ma, Y-R; Xu, L-P; Zhang, X-H; Yan, C-H; Wang, Y; Wang, F-R; Wang, J-Z; Chen, Y; Han, W; Chen, Y-H; Chen, H; Liu, K-Y; Huang, X-J

2017-03-01

We investigated the impact of donor type on post-relapse survival (PRS) in 85 patients with hematological relapse after their first allogeneic hematological stem cell transplantation (allo-HSCT) for hematological malignancy. The median follow-up was 64 months among survivors. Both 3-year overall survival and 3-year PRS were similar in haploidentical donor (HID) and matched sibling donor (MRD) transplantation (13.0%±4.7% vs 19.4%±7.1%, P=0.913 and 7.7±3.9% vs 9.7±5.3%, P= 0.667). Higher rates of post-relapse grade II-IV and III-IV acute GvHD (aGvHD) were observed in HID transplantation patients. A higher cumulative incidence of post-relapse extensive chronic GvHD was also observed for HID transplantation patients. Multivariate analyses confirmed that treatment including donor lymphocyte infusion (DLI), late relapse >1 year, and in first CR at transplantation were associated with superior PRS (P=0.012, hazard ratio (HR)=0.527 (0.320-0.866)); P=0.033, HR=0.534 (0.300-0.952) and P=0.046, HR=0.630 (0.400-0.992). The data suggest that post-relapse outcomes are comparable in HID and MRD transplantation, and that DLI is safe for relapsed patients after haploidentical transplantation.

Context-induced relapse after extinction versus punishment: similarities and differences.

PubMed

Marchant, Nathan J; Campbell, Erin J; Pelloux, Yann; Bossert, Jennifer M; Shaham, Yavin

2018-05-24

Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drug-reinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies.

Predictors of smoking cessation and relapse in older adults.

PubMed Central

Salive, M E; Cornoni-Huntley, J; LaCroix, A Z; Ostfeld, A M; Wallace, R B; Hennekens, C H

1992-01-01

We examined longitudinal changes in smoking behavior among older adults in three community cohorts of the Established Populations for Epidemiologic Studies of the Elderly. Smoking prevalence declined from 15% at baseline to 9% during 6 years of follow-up. Annual smoking cessation and relapse rates were 10% and less than 1%, respectively. Interval diagnosis of myocardial infarction, stroke, or cancer increased subsequent smoking cessation but not relapse. Although smoking cessation around diagnosis is increased, primary prevention could yield greater benefits. PMID:1503170

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.

Relapse after Oral Terbinafine Therapy in Dermatophytosis: A Clinical and Mycological Study.

PubMed

Majid, Imran; Sheikh, Gousia; Kanth, Farhath; Hakak, Rubeena

2016-01-01

The incidence of recurrent tinea infections after oral terbinafine therapy is on the rise. This study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris. A total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study. The enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients were then followed up for 12 weeks to look for any relapse/cure. The common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral terbinafine therapy, 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture (persisters) at this time. These culture positive patients included all the clinically positive cases. Rest of the patients (65/100) demonstrated both clinical and mycological cure at this time (cured). Over the 12-week follow-up, clinical relapse was seen in 22 more patients (relapse) among those who had shown clinical and mycological cure at the end of terbinafine therapy. Thus, only 43% patients could achieve a long-term clinical and mycological cure after 2 weeks of oral terbinafine treatment. Majority of the relapses (16/22) were seen after 8 weeks of completion of treatment. There was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured, persister, or relapse groups. Incomplete mycological cure as well as relapse is very common after standard (2-week) terbinafine therapy in our patients of tinea cruris/corporis.

Baclofen as relapse prevention in the treatment of gamma-hydroxybutyrate dependence: a case series.

PubMed

Kamal, Rama M; Loonen, Anton J M; Dijkstra, Boukje A G; De Jong, Cornelis A J

2015-06-01

In the last decade, gamma-hydroxybutyrate (GHB) abuse and dependence have increased. It has been reported that GHB dependence has a high rate of relapse, serious complications of intoxication, and a potentially life-threatening withdrawal syndrome. Nevertheless, in clinical practice, there is no known medical treatment to support GHB relapse prevention. We describe a case series of patients who were supported through an off-label treatment with baclofen to avoid a relapse into GHB abuse, for a period of 12 weeks. Nine of 11 patients did not relapse while taking a dose ranging from 30 to 60 mg per day, one patient relapsed after 5 weeks, and one stopped after 7 weeks. Baclofen was well tolerated; patients reported mild side effects such as fatigue, nausea, dry mouth, excessive sweating, and depressive feelings. Although systematic evidence is still lacking, our practice-based experience suggests that treatment with baclofen to assist abstinence might be effective in patients with GHB dependence. Further systematic controlled studies are necessary to establish the exact efficacy and safety of baclofen as relapse prevention for GHB-dependent patients.

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

Advanced-stage Hodgkin lymphoma: US/chest radiography for detection of relapse in patients in first complete remission--a randomized trial of routine surveillance imaging procedures.

PubMed

Picardi, Marco; Pugliese, Novella; Cirillo, Michele; Zeppa, Pio; Cozzolino, Imma; Ciancia, Giuseppe; Pettinato, Guido; Salvatore, Claudia; Quintarelli, Concetta; Pane, Fabrizio

2014-07-01

To compare the use of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) with the use of a combination of ultrasonography (US) and chest radiography for systematic follow-up of patients with high-risk Hodgkin lymphoma. Institutional review board approval and informed consent were obtained. In a single center between January 2001 and December 2009, patients with advanced-stage Hodgkin lymphoma who had responded completely to first-line treatment were randomly assigned (1:1) to follow-up with either PET/CT or US/chest radiography. Follow-up included clinical and imaging procedures at 4, 8, 12, 16, 20, 24, 30, 36, 48, 60, 84, and 108 months after treatment discontinuation. When clinical and/or imaging results were positive, recurrence was confirmed histologically. The primary endpoint was to compare the sensitivity of the two follow-up imaging approaches. Secondary endpoints were their specificity, positive and negative predictive values, time to recurrence detection, radiation risks, and costs. A total of 300 patients were randomized into the two arms. The study was closed after a median follow-up time of 60 months, with a relapse rate of 27%. Sensitivity for detection of Hodgkin lymphoma was similar for the two follow-up approaches. All of the relapses (40 of 40) were identified with FDG PET/CT (100%) and 39 of 40 relapses were identified with US/chest radiography (97.5%; P = .0001 for the equivalence test). US/chest radiography showed significantly higher specificity and positive predictive value than did PET/CT (96% [106 of 110] vs 86% [95 of 110], respectively; P = .02; and 91% [39 of 43] vs 73% [40 of 55], respectively; P = .01). Exposure to ionizing radiation was estimated to be 14.5 mSv for one PET/CT examination versus 0.1 mSv for one chest radiographic examination. Estimated cost per relapse diagnosed with routine PET/CT was 10-fold higher compared with that diagnosed with routine US/chest radiography. US and

Relapses and recurrences of catatonia: 30-case analysis and literature review.

PubMed

Lin, Chin-Chuen; Hung, Yi-Yung; Tsai, Meng-Chang; Huang, Tiao-Lai

2016-04-01

Relieving catatonia helps identify the underlying etiology and its treatment. However, catatonia may reemerge after some time, but there are few data on the relapses and recurrences of catatonia. We aimed to investigate the characteristics of patients with relapses or recurrences of catatonia as well as the efficacy of the lorazepam-diazepam protocol on them. Patients with catatonia who had more than one episode of catatonia and were treated with the lorazepam-diazepam protocol were identified. Their medical charts were reviewed, and interview was conducted. Thirty patients were identified. Nineteen (63.3%) were diagnosed with schizophrenia, five (16.7%) with major depressive disorder, two (6.7%) with bipolar disorder, and four (13.3%) with general medical conditions. In the 68 relapses and relapses the lorazepam-diazepam protocol was used, full response was reported in 54 (79.4%) of them. Twelve of 19 (63.2%) patients with schizophrenia were treated with clozapine. Twenty (66.7%) out of 30 patients were maintained on oral lorazepam by the time of discharge. Literature review showed similar prevalence of schizophrenia in patients with more than one episode of catatonia, and a wide variety of treatment options. The lorazepam-diazepam protocol was mostly effective in managing relapses and recurrences of catatonia. Maintenance clozapine and oral lorazepam were beneficial in a significant number of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

Gene Expression Profiling of Acute Lymphoblastic Leukemia in Children with Very Early Relapse.

PubMed

Núñez-Enríquez, Juan Carlos; Bárcenas-López, Diego Alberto; Hidalgo-Miranda, Alfredo; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina; Flores-Lujano, Janet; Solis-Labastida, Karina Anastacia; Martínez-Morales, Gabriela Bibiana; Sánchez-Muñoz, Fausto; Espinoza-Hernández, Laura Eugenia; Velázquez-Aviña, Martha Margarita; Merino-Pasaye, Laura Elizabeth; García Velázquez, Alejandra Jimena; Pérez-Saldívar, María Luisa; Mojica-Espinoza, Raúl; Ramírez-Bello, Julián; Jiménez-Morales, Silvia; Mejía-Aranguré, Juan Manuel

2016-11-01

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis. Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools. BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change >2.0 and p value <0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction. Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Reaching the limits of reciprocity in favor exchange: The effects of generous, stingy, and matched favor giving on social status.

PubMed

Ouyang, Kan; Xu, Erica; Huang, Xu; Liu, Wu; Tang, Yipeng

2018-03-08

Group members gain social status via giving favors to others, but why and when they do so remain unclear in the literature. Building on social exchange theory and social status literature, we identify three types of favor giving among group members (generous, stingy, and matched) and propose that an affective mechanism (i.e., gratitude) and a cognitive mechanism (i.e., perceived competence) underlie the relationship between favor giving and status attainment. Specifically, generous/stingy favor giving has a linear relationship with status attainment through both gratitude and perceived competence, whereas matched favor giving has a curvilinear relationship with status attainment only through perceived competence. An experimental study and a field study lend support to our propositions. Our study complements the literature by offering a complete picture of how three types of favor giving among group members shape their social status in different ways. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Disrupted coupling of large-scale networks is associated with relapse behaviour in heroin-dependent men

PubMed Central

Li, Qiang; Liu, Jierong; Wang, Wei; Wang, Yarong; Li, Wei; Chen, Jiajie; Zhu, Jia; Yan, Xuejiao; Li, Yongbin; Li, Zhe; Ye, Jianjun; Wang, Wei

2018-01-01

Background It is unknown whether impaired coupling among 3 core large-scale brain networks (salience [SN], default mode [DMN] and executive control networks [ECN]) is associated with relapse behaviour in treated heroin-dependent patients. Methods We conducted a prospective resting-state functional MRI study comparing the functional connectivity strength among healthy controls and heroin-dependent men who had either relapsed or were in early remission. Men were considered to be either relapsed or in early remission based on urine drug screens during a 3-month follow-up period. We also examined how the coupling of large-scale networks correlated with relapse behaviour among heroin-dependent men. Results We included 20 controls and 50 heroin-dependent men (26 relapsed and 24 early remission) in our analyses. The relapsed men showed greater connectivity than the early remission and control groups between the dorsal anterior cingulate cortex (key node of the SN) and the dorsomedial prefrontal cortex (included in the DMN). The relapsed men and controls showed lower connectivity than the early remission group between the left dorsolateral prefrontal cortex (key node of the left ECN) and the dorsomedial prefrontal cortex. The percentage of positive urine drug screens positively correlated with the coupling between the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex, but negatively correlated with the coupling between the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Limitations We examined deficits in only 3 core networks leading to relapse behaviour. Other networks may also contribute to relapse. Conclusion Greater coupling between the SN and DMN and lower coupling between the left ECN and DMN is associated with relapse behaviour. These findings may shed light on the development of new treatments for heroin addiction. PMID:29252165

Opposite Effects of Basolateral Amygdala Inactivation on Context-Induced Relapse to Cocaine Seeking after Extinction versus Punishment.

PubMed

Pelloux, Yann; Minier-Toribio, Angelica; Hoots, Jennifer K; Bossert, Jennifer M; Shaham, Yavin

2018-01-03

Studies using the renewal procedure showed that basolateral amygdala (BLA) inactivation inhibits context-induced relapse to cocaine-seeking after extinction. Here, we determined whether BLA inactivation would also inhibit context-induced relapse after drug-reinforced responding is suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to adverse consequences of drug use. We also determined the effect of central amygdala (CeA) inactivation on context-induced relapse.We trained rats to self-administer cocaine for 12 d (6 h/d) in Context A and then exposed them to either extinction or punishment training for 8 d in Context B. During punishment, 50% of cocaine-reinforced lever-presses produced an aversive footshock of increasing intensity (0.1-0.5 or 0.7 mA). We then tested the rats for relapse to cocaine seeking in the absence of cocaine or shock in Contexts A and B after BLA or CeA injections of vehicle or GABA agonists (muscimol-baclofen). We then retrained the rats for cocaine self-administration in Context A, repunished or re-extinguished lever pressing in Context B, and retested for relapse after BLA or CeA inactivation.BLA or CeA inactivation decreased context-induced relapse in Context A after extinction in Context B. BLA, but not CeA, inactivation increased context-induced relapse in Context A after punishment in Context B. BLA or CeA inactivation provoked relapse in Context B after punishment but not extinction. Results demonstrate that amygdala's role in relapse depends on the method used to achieve abstinence and highlights the importance of studying relapse under abstinence conditions that more closely mimic the human condition. SIGNIFICANCE STATEMENT Relapse to drug use during abstinence is often provoked by re-exposure to the drug self-administration environment or context. Studies using the established extinction-reinstatement rodent model of drug relapse have shown that inactivation of the basolateral amygdala

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

PubMed

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

2017-04-01

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

[Relapse in schizophrenia: an exploratory study of the joint conceptions of patients, parents and caregivers].

PubMed

Koenig, M; Castillo, M-C; Urdapilleta, I; Le Borgne, P; Bouleau, J-H

2011-06-01

The question of the course of schizophrenia relapses, is of considerable interest in different clinical and social areas such as prognosis, quality of life, therapeutic relationship, psychoeducation, rehabilitation and so on. The more the schizophrenic relapses, the higher the level of handicap. Although there is a widespread agreement that it is essential to detect early signs of relapses in order to prevent them, there still remain theoretical and methodological difficulties in identifying these signs because they are personal, heterogeneous and not always specific to psychosis. That is why the notion of "relapse signature" seems relevant by taking into account differentiated and personal assessment of early signs of relapse. This implies the consideration of the different visions of relapse given by patients, parents and caregivers. We propose a qualitative study of the joint appraisal of patients, patients' parents and medical staff. The aim of this study is to regroup the expertises in order to further our understanding of the early signs of relapse. We assume that patients and parents are able to describe signs that are not considered as pathological symptoms, but refer to a personal manner of initiating the relapse process. This should then help in designing early intervention and provide reinforced therapeutic alliance and more positive responses to psychoeducation programs. We have interviewed 30 subjects divided in three groups: 10 schizophrenic patients, 10 caregivers (including physicians, psychologists and nurses) and 10 parents of schizophrenics. The patients met the following criteria: patients with a diagnosis of schizophrenia (DSM IV criteria), under neuroleptic treatment, and stabilized. The mean duration of illness was 15 years. The patients as well as caregivers were recruited in two external hospital structures. All the subjects gave their written consent for this study and its methods. We did not recruit parents who were not living with their

Direct and indirect cost burden associated with multiple sclerosis relapses: excess costs of persons with MS and their spouse caregivers.

PubMed

Parisé, Hélène; Laliberté, François; Lefebvre, Patrick; Duh, Mei Sheng; Kim, Edward; Agashivala, Neetu; Abouzaid, Safiya; Weinstock-Guttman, Bianca

2013-07-15

MS relapses are unpredictable and can be concerning to patients and their caregivers. To assess the direct and indirect cost burden associated with relapses of different severities in MS patients and with MS relapse frequency on spouse caregivers. Using a U.S. insurance claims and employee disability database (1999-2011), we studied adult MS patients (ICD-9-CM: 340.x) and their spouse caregivers. A previously published algorithm to identify relapses was used to stratify: (1) MS patients into cohorts of no, low/moderate, and high severity relapse based on the most severe relapse within one year of follow-up (if any); (2) caregivers into cohorts of no, less, and more frequent relapses based on the overall frequency of relapses of their spouse. Adjusted cost differences and 95% confidence intervals evaluating the yearly incremental costs at 12 months of follow-up (MS patients) and overall (caregivers) associated with relapses are reported. Among the 9421 MS patients (N: no relapse=7686; low/moderate severity relapse=1220; high severity relapse=515) identified, both relapse cohorts incurred significantly higher annual incremental direct costs than the no relapse cohort (low/moderate severity=$8269 [6565-10,115]; high severity=$24,180 [20,263-28,482]) and indirect costs (low/moderate severity=$1429 [759-2147]; high severity=$2714 [1468-4035]). More frequent relapses versus no relapse also translated into a significantly greater cost burden for caregivers (direct+indirect=$1725 [376-2885]) but less frequent relapses did not. Relapse severity was significantly and increasingly associated with greater direct and indirect costs in MS patients. More frequent relapses also translated into a significant cost burden in spouse caregivers. Copyright © 2013 Elsevier B.V. All rights reserved.

Plasma exchange therapy in steroid-unresponsive relapses in patients with multiple sclerosis.

PubMed

Trebst, Corinna; Reising, Ansgar; Kielstein, Jan T; Hafer, Carsten; Stangel, Martin

2009-01-01

Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS). We report our experiences of PE therapy in a series of 20 patients with 21 steroid unresponsive MS relapses. A marked-to-moderate clinical response with clear gain of function in 76% of patients with uni- or bilateral optic neuritis and in 87.5% of patients with relapses other than optic neuritis was observed. PE is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses.

Testing the transtheoretical model in predicting smoking relapse among Malaysian adult smokers receiving assistance in quitting.

PubMed

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

2013-01-01

The role of The Transtheoretical Model (TTM) in predicting relapse is limited. We aimed to assess whether this model can be utilised to predict relapse during the action stage. The participants included 120 smokers who had abstained from smoking for at least 24 hours following two Malaysian universities' smoking cessation programme. The smokers who relapsed perceived significantly greater advantages related to smoking and increasing doubt in their ability to quit. In contrast, former smokers with greater self-liberation and determination to abstain were less likely to relapse. The findings suggest that TTM can be used to predict relapse among quitting smokers.

Increased risk of multiple sclerosis relapse after in vitro fertilisation.

PubMed

Michel, Laure; Foucher, Yohann; Vukusic, Sandra; Confavreux, Christian; de Sèze, Jérome; Brassat, David; Clanet, Michel; Clavelou, Pierre; Ouallet, Jean-Christophe; Brochet, Bruno; Pelletier, Jean; Labauge, Pierre; Lebrun, Christine; Lepage, Emmanuelle; Le Frere, Fabienne; Jacq-Foucher, Marylène; Barriere, Paul; Wiertlewski, Sandrine; Laplaud, David-Axel

2012-08-01

Exogenous sexual steroids together with pregnancy have been shown to influence the risk of relapses in multiple sclerosis (MS). Treatments used during assisted reproductive techniques may consequently influence the short term evolution of MS by modifying the hormonal status of the patient. The objective of this study was to determine if there was an increased risk of developing exacerbations in women with MS after in vitro fertilisation (IVF). MS and IVF data were either automatically extracted from 13 French university hospital databases or obtained from referring neurologists. After matching databases, patient clinical files were systematically reviewed to collect information about MS and the treatments used for IVF. The association between IVF and the occurrence of MS relapses was analysed in detail using univariate and multivariate statistical tests. During the 11 year study period, 32 women with MS had undergone 70 IVF treatments, 48 using gonadotrophin releasing hormone (GnRH) agonists and 19 using GnRH antagonists. A significant increase in the annualised relapse rate (ARR) was observed during the 3 month period following IVF (mean ARR 1.60, median ARR 0) compared with the same period just before IVF (mean ARR 0.80, median ARR 0) and to a control period 1 year before IVF (mean ARR 0.68, median ARR 0). The significant increase in relapses was associated with the use of GnRH agonists (Wilcoxon paired test, p=0.025) as well as IVF failure (Wilcoxon paired test, p=0.019). An increased relapse rate was observed in this study after IVF in patients with MS and may be partly related both to IVF failure and the use of GnRH agonists.

Three-Drug Combination for Relapsed Multiple Myeloma

Cancer.gov

A summary of Interim results from an international, randomized phase III trial that suggest that adding carfilzomib (Kyprolis®) to a standard treatment improves outcomes for patients with multiple myeloma whose cancer has relapsed.

Vincristine, Irinotecan, and Bevacizumab in Relapsed Wilms Tumor With Diffuse Anaplasia.

PubMed

Schiavetti, Amalia; Varrasso, Giulia; Collini, Paola; Clerico, Anna

2018-05-01

The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.

Repeated aripiprazole administration attenuates cocaine seeking in a rat model of relapse.

PubMed

Feltenstein, Matthew W; Do, Phong H; See, Ronald E

2009-12-01

Aripiprazole (Abilify) is an atypical antipsychotic drug characterized by partial agonist activity at dopamine (DA) D(2)/D(3) receptors and a low side-effect profile. While we previously demonstrated that acute aripiprazole blocked the reinstatement of cocaine seeking in an animal model of relapse, clinical treatment of relapse prevention necessitates testing the effects of aripiprazole following prolonged abstinence, as well as after repeated administration during withdrawal from cocaine. We assessed the effects of repeated aripiprazole treatment on cocaine seeking after abstinence and during conditioned cue-induced and cocaine-primed reinstatement in rats. Rats self-administered intravenous cocaine paired with a light + tone stimulus for 10-14 days, followed by 2 weeks of abstinence. Following post-abstinence relapse testing, lever responding was allowed to extinguish, with subsequent reinstatement testing occurring either in the presence of the conditioned stimulus, or after a cocaine-priming injection (10 mg/kg, intraperitoneal (IP)). Following 3 or 7 days of pretreatment, rats received an injection of aripiprazole (0.25, 0.5, and 1.0 mg/kg, IP) or vehicle prior to post-abstinence relapse and reinstatement testing. Vehicle-pretreated animals showed robust cocaine seeking during relapse and reinstatement testing, an effect that was significantly attenuated by aripiprazole pretreatment, although no lasting effects were found in the absence of acute injection. These findings support the possibility that repeated aripiprazole may be an effective therapeutic agent for the prevention of relapse in abstinent cocaine users. Based on its antipsychotic profile, aripiprazole may be particularly useful for individuals diagnosed with comorbid psychoses, such as schizophrenia or bipolar disorder.

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.

Deafness due to haemorrhagic labyrinthitis and a review of relapses in Streptococcus suis meningitis.

PubMed

Tan, J H; Yeh, B I; Seet, C S R

2010-02-01

Deafness is a common and often permanent neurological sequel of Streptococcus (S.) suis meningitis. Suppurative labyrinthitis, rather than direct auditory nerve infection, has been found to be the site responsible for deafness. Neuroimaging is important to localise the site involved in hearing loss and to assess the feasibility of a cochlear implantation. S. suis is very sensitive to penicillin. Although a relapse of S. suis meningitis is uncommon, it can occur despite an adequate duration of appropriate antibiotic therapy. We describe a patient with S. suis meningitis, who developed permanent deafness from haemorrhagic labyrinthitis, as shown on magnetic resonance imaging. She suffered a relapse despite a seven-week course of intravenous antibiotics. A review on six cases of relapse reported in the literature shows that relapses occurred despite two to four weeks of antibiotics being administered to the patients. The clinical implications and treatment of relapse are discussed.

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

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

Prevention and treatment of relapse after stem cell transplantation by cellular therapies.

PubMed

Falkenburg, Fred; Ruggiero, Eliana; Bonini, Chaira; Porter, David; Miller, Jeff; Malard, Floran; Mohty, Mohamad; Kröger, Nicolaus; Kolb, Hans Jochem

2018-05-24

Despite recent advances in reducing therapy-related mortality after allogeneic stem cell transplantation (alloSCT) relapse remains the major cause of treatment failure and little progress has been achieved in the last decades. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg/Germany in November 2016 international experts presented and discussed recent developments in the field. Here, the potential of cellular therapies including unspecific and specific T cells, genetically modified T cells, CAR-T cells, NK-cells, and second allografting in prevention and treatment of relapse after alloSCT are summarized.

THE IMPACT OF STRESSFUL LIFE EVENTS ON RELAPSE OF GENERALIZED ANXIETY DISORDER

PubMed Central

Francis, Jennifer L.; Moitra, Ethan; Dyck, Ingrid; Keller, Martin B.

2013-01-01

Background Stressful life events (SLEs) are associated with the onset of psychiatric disorders but little is known about the effects of SLEs on individuals already diagnosed with an anxiety disorder, particularly generalized anxiety disorder (GAD) in which worry about life events is a defining characteristic. This study examined the impact of SLEs on relapse in adults already diagnosed with GAD. Methods Data are obtained from the Harvard/Brown Anxiety Research Project (HARP), a naturalistic longitudinal study of adults with a current or past history of anxiety disorders. One hundred and twelve adults recovered from an episode of GAD and 27 subsequently relapsed during the study. Eight categories of SLEs were assessed via interview and were examined as predictors of GAD relapse. Results An increased total number of SLEs was associated with a higher cumulative probability of relapse into episode of GAD and there was a nonsignificant statistical trend indicating specific categories of SLEs including health, death, and family/friends/household were related to an increased probability of relapse into episodes of GAD. Conclusions SLEs impact the course of GAD and certain types of stressors may be more relevant to symptomatology than others. The change and uncertainty associated with SLEs may exacerbate existing worry tendencies even among those who have recovered from GAD. PMID:22431499

The impact of stressful life events on relapse of generalized anxiety disorder.

PubMed

Francis, Jennifer L; Moitra, Ethan; Dyck, Ingrid; Keller, Martin B

2012-05-01

Stressful life events (SLEs) are associated with the onset of psychiatric disorders but little is known about the effects of SLEs on individuals already diagnosed with an anxiety disorder, particularly generalized anxiety disorder (GAD) in which worry about life events is a defining characteristic. This study examined the impact of SLEs on relapse in adults already diagnosed with GAD. Data are obtained from the Harvard/Brown Anxiety Research Project (HARP), a naturalistic longitudinal study of adults with a current or past history of anxiety disorders. One hundred and twelve adults recovered from an episode of GAD and 27 subsequently relapsed during the study. Eight categories of SLEs were assessed via interview and were examined as predictors of GAD relapse. An increased total number of SLEs was associated with a higher cumulative probability of relapse into episode of GAD and there was a nonsignificant statistical trend indicating specific categories of SLEs including health, death, and family/friends/household were related to an increased probability of relapse into episodes of GAD. SLEs impact the course of GAD and certain types of stressors may be more relevant to symptomatology than others. The change and uncertainty associated with SLEs may exacerbate existing worry tendencies even among those who have recovered from GAD. © 2012 Wiley Periodicals, Inc.

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.

Whole Neuraxis Irradiation to Address Central Nervous System Relapse in High-Risk Neuroblastoma

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

Croog, Victoria J., E-mail: vcroog@sibley.or; Kramer, Kim; Cheung, Nai-Kong V.

Background: As systemic control of high-risk neuroblastoma (NB) has improved, relapse in the central nervous system (CNS) is an increasingly recognized entity that carries a grim prognosis. This study describes the use of craniospinal irradiation (CSI) for CNS relapse and compares outcomes to patients who received focal radiotherapy (RT). Methods: A retrospective query identified 29 children with NB treated at Memorial Sloan-Kettering Cancer Center since 1987 who received RT for CNS relapse. At CNS relapse, 16 patients received CSI (median dose, 2160cGy), and 13 received focal RT. Of those who underwent CSI, 14 (88%) received intra-Ommaya (IO) radioimmunotherapy (RIT); onemore » patient in the non-CSI cohort received IO-RIT. Results: Patient characteristics were similar between the groups. Time to CNS relapse was 20 and 17 months for the CSI and non-CSI cohorts, respectively. At a median follow-up of 28 months, 12 patients (75%) in the CSI group are alive without CNS disease, including two patients with isolated skeletal relapse. Another patient is alive without disease after a brain relapse was retreated with RT. Three patients died-one with no NB at autopsy, one of CNS disease, and one of systemic disease. The two patients who died of NB did not receive IO-RIT. All 13 patients in the non-CSI cohort died at a median of 8.8 months. Conclusions: Low-dose CSI together with IO-RIT provides durable CNS remissions and improved survival compared with focal RT and conventional therapies. Further evaluation of long-term NB survivors after CSI is warranted to determine the treatment consequences for this cohort.« less

Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence

PubMed Central

Campbell, Erin J.; Whitaker, Leslie R.; Harvey, Brandon K.; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T.; Heins, Robert C.; Prisinzano, Thomas E.; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M.

2016-01-01

In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. SIGNIFICANCE STATEMENT In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol

Role of Ventral Subiculum in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence.

PubMed

Marchant, Nathan J; Campbell, Erin J; Whitaker, Leslie R; Harvey, Brandon K; Kaganovsky, Konstantin; Adhikary, Sweta; Hope, Bruce T; Heins, Robert C; Prisinzano, Thomas E; Vardy, Eyal; Bonci, Antonello; Bossert, Jennifer M; Shaham, Yavin

2016-03-16

In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-administer alcohol in one context (A), punish the alcohol-reinforced responding in a different context (B), and then test for relapse to alcohol seeking in Contexts A and B without alcohol or shock. Here, we studied the role of projections to nucleus accumbens (NAc) shell from ventral subiculum (vSub), basolateral amygdala, paraventricular thalamus, and ventral medial prefrontal cortex in context-induced relapse after punishment-imposed abstinence. First, we measured double-labeling of the neuronal activity marker Fos with the retrograde tracer cholera toxin subunit B (injected in NAc shell) and demonstrated that context-induced relapse is associated with selective activation of the vSub→NAc shell projection. Next, we reversibly inactivated the vSub with GABA receptor agonists (muscimol+baclofen) before the context-induced relapse tests and provided evidence for a causal role of vSub in this relapse. Finally, we used a dual-virus approach to restrict expression of the inhibitory κ opioid-receptor based DREADD (KORD) in vSub→NAc shell projection neurons. We found that systemic injections of the KORD agonist salvinorin B, which selectively inhibits KORD-expressing neurons, decreased context-induced relapse to alcohol seeking. Our results demonstrate a critical role of vSub in context-induced relapse after punishment-imposed abstinence and further suggest a role of the vSub→NAc projection in this relapse. In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol use. Until recently, an

Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

ERIC Educational Resources Information Center

Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

2008-01-01

The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

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

Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

PubMed

Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

2017-10-12

To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

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

Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

ClinicalTrials.gov

2018-03-05

Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

Application of Neurolinguistic Programming for Treatment and Relapse Prevention of Addictive Behaviors.

ERIC Educational Resources Information Center

Sandhu, Daya Singh

The dilemma of relapse exists for a number of addictive behaviors, and mental health authorities agree that keeping addictive behaviors off permanently is much more difficult than treating the behaviors initially. Several relapse prevention models have been posited and environmental, physiological, behavioral, cognitive, and affective factors have…

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…

Why Koreans are More Likely to Favor "Apology," While Americans are More Likely to Favor "Thank You"

ERIC Educational Resources Information Center

Lee, Hye Eun; Park, Hee Sun

2011-01-01

Two studies investigated whether apologies or thanks are preferred in asking favors in the United States and Korea, and how this relates to perceptions of reduction in positive and negative face threats. In the first study (n = 224), participants composed an e-mail message where a favor was asked. In the second (n = 807), participants completed…

25 CFR 700.519 - Gifts, entertainment and favors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false Gifts, entertainment and favors. 700.519 Section 700.519... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities, including gifts, entertainment and favors, (no matter how innocently tendered or received) from those who...

25 CFR 700.519 - Gifts, entertainment and favors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 2 2014-04-01 2014-04-01 false Gifts, entertainment and favors. 700.519 Section 700.519... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities, including gifts, entertainment and favors, (no matter how innocently tendered or received) from those who...

25 CFR 700.519 - Gifts, entertainment and favors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 2 2012-04-01 2012-04-01 false Gifts, entertainment and favors. 700.519 Section 700.519... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities, including gifts, entertainment and favors, (no matter how innocently tendered or received) from those who...

25 CFR 700.519 - Gifts, entertainment and favors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 2 2013-04-01 2013-04-01 false Gifts, entertainment and favors. 700.519 Section 700.519... Employee Responsibility and Conduct § 700.519 Gifts, entertainment and favors. (a) Acceptance of gratuities, including gifts, entertainment and favors, (no matter how innocently tendered or received) from those who...

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

The role of histology in forensic autopsies: is histological examination always necessary to determine a cause of death?

PubMed

Fronczek, Judith; Hollingbury, Frances; Biggs, Michael; Rutty, Guy

2014-03-01

In England and Wales there is a conflict between the law and advice from regulatory bodies in relation to the sampling of human tissue for histological examination following medico-legal post-mortem examinations. Considering the results of previous publications, we performed a specific study to investigate the role of histology in determining the cause of death in cases at a forensic unit. A retrospective study of 500 adult forensic cases was performed. Cases were categorized by the role the histological examination played in determining a cause of death and its contributory factors. Furthermore, cause of death, manner of death, organ systems involved, and discrepancies were assessed. Of the 500 cases, histology was undertaken in 287 cases (58 %). Microscopic examination provided the cause of death in 2 % of cases where histology had been undertaken, and it added to the cause of death in 8 %. In 61 % of cases microscopy confirmed the macroscopic findings, and in 30 % it did not influence the medical cause of death. Histological examination of all organs in all forensic cases for the purpose of providing a medical cause of death is not supported. Practice guidance should be adjusted to reflect that, while histological examination is essential in certain circumstances, the decision to retain material for histology should be made on a case by case basis at the pathologist's discretion.

Predictors of Relapse for American Indian Women after Substance Abuse Treatment

ERIC Educational Resources Information Center

Chong, Jenny; Lopez, Darlene

2008-01-01

The objective of this study was to describe the predictors of substance use relapse of American Indian (AI) women up to one year following substance abuse treatment. Relapse is defined as any use of alcohol or drugs in the past 30 days at the follow-up points. Data were collected from AI women in a 45-day residential substance abuse treatment…

Copy number profiling of adult relapsed B-cell precursor acute lymphoblastic leukemia reveals potential leukemia progression mechanisms.

PubMed

Ribera, Jordi; Zamora, Lurdes; Morgades, Mireia; Mallo, Mar; Solanes, Neus; Batlle, Montserrat; Vives, Susana; Granada, Isabel; Juncà, Jordi; Malinverni, Roberto; Genescà, Eulàlia; Guàrdia, Ramon; Mercadal, Santiago; Escoda, Lourdes; Martinez-Lopez, Joaquín; Tormo, Mar; Esteve, Jordi; Pratcorona, Marta; Martinez-Losada, Carmen; Solé, Francesc; Feliu, Evarist; Ribera, Josep-Maria

2017-11-01

The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe-dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1, and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B-cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies. © 2017 Wiley Periodicals, Inc.

Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse.

PubMed

Ogden, Angela; Rida, Padmashree C G; Knudsen, Beatrice S; Kucuk, Omer; Aneja, Ritu

2015-10-28

Although docetaxel significantly improves survival in a variety of malignancies, its clinical utility is severely restricted by acquired chemoresistance and disease relapse. To uncover the mechanisms underlying these all too common occurrences, an abundance of research has focused on mutations and gene expression patterns; however, these findings are yet to translate into improved outcomes for patients being administered this drug. These analyses have overlooked a promising lead in the quest to discern key mediators of resistance and relapse following docetaxel therapy: polyploidization. This process is manifested following docetaxel-mediated mitotic arrest by the appearance of giant, multinucleated cells, which slipped from mitosis without undergoing cytokinesis. Polyploid cells generally possess supernumerary centrosomes, are chromosomally instable, and resist chemotherapy. We thus suspect that chemoresistance and relapse following treatment with docetaxel might be combatted by co-administration of centrosome declustering drugs, which could selectively destroy polyploid cells given that normal cells do not possess amplified centrosomes, an intriguing paradigm that warrants further investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

11 CFR 7.20 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 11 Federal Elections 1 2011-01-01 2011-01-01 false Gifts, entertainment, and favors. 7.20 Section... of Special Commission Employees § 7.20 Gifts, entertainment, and favors. Except as provided at 11 CFR... a gift, gratuity, loan, entertainment, or favor for himself or herself, or for another person...

11 CFR 7.20 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Gifts, entertainment, and favors. 7.20 Section... of Special Commission Employees § 7.20 Gifts, entertainment, and favors. Except as provided at 11 CFR... a gift, gratuity, loan, entertainment, or favor for himself or herself, or for another person...

Sequential treatment with fluoxetine and relapse--prevention CBT to improve outcomes in pediatric depression.

PubMed

Kennard, Betsy D; Emslie, Graham J; Mayes, Taryn L; Nakonezny, Paul A; Jones, Jessica M; Foxwell, Aleksandra A; King, Jessica

2014-10-01

The authors evaluated a sequential treatment strategy of fluoxetine and relapse-prevention cognitive-behavioral therapy (CBT) to determine effects on remission and relapse in youths with major depressive disorder. Youths 8-17 years of age with major depression were treated openly with fluoxetine for 6 weeks. Those with an adequate response (defined as a reduction of 50% or more on the Children's Depression Rating Scale-Revised [CDRS-R]) were randomly assigned to receive continued medication management alone or continued medication management plus CBT for an additional 6 months. The CBT was modified to address residual symptoms and was supplemented by well-being therapy. Primary outcome measures were time to remission (with remission defined as a CDRS-R score of 28 or less) and rate of relapse (with relapse defined as either a CDRS-R score of 40 or more with a history of 2 weeks of symptom worsening, or clinical deterioration). Of the 200 participants enrolled in acute-phase treatment, 144 were assigned to continuation treatment with medication management alone (N=69) or medication management plus CBT (N=75). During the 30-week continuation treatment period, time to remission did not differ significantly between treatment groups (hazard ratio=1.26, 95% CI=0.87, 1.82). However, the medication management plus CBT group had a significantly lower risk of relapse than the medication management only group (hazard ratio=0.31, 95% CI=0.13, 0.75). The estimated probability of relapse by week 30 was lower with medication management plus CBT than with medication management only (9% compared with 26.5%). Continuation-phase relapse-prevention CBT was effective in reducing the risk of relapse but not in accelerating time to remission in children and adolescents with major depressive disorder.

Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss.

PubMed

Mata-Castro, Nieves; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

2018-03-01

Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse. The mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03). Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Postpartum Smoking Relapse and Breast Feeding: Defining the Window of Opportunity for Intervention.

PubMed

Logan, Chad A; Rothenbacher, Dietrich; Genuneit, Jon

2017-03-01

Though many women spontaneously quit smoking during pregnancy, a large proportion relapse after delivery. Efforts aimed at reducing postpartum smoking relapse have been largely ineffective. Several studies have reported breast feeding as a primary factor influencing smoking abstinence duration. However, data on the potential role of breast feeding in smoking intervention efforts remain incomplete. The Ulm SPATZ Health Study cohort consists of 1006 newborns of 970 mothers recruited in the University Medical Center Ulm, Germany. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used to assess differences in predominant and total breast-feeding duration stratified by smoking abstinence at 2 years and relapse period (by 6 weeks, 6 months, and 2 years postdelivery). Chi-square and Kruskal-Wallis tests were performed to identify significant differences in demographic and lifestyle factors across smoking categories. Approximately 70% of previous smokers who initiated breast feeding relapsed within 2 years. Relapse by 6 months was significantly associated with noninitiation of predominant breast feeding. Total breast-feeding duration rates among abstaining mothers and those who relapsed after 6 weeks mirrored those of nonsmokers respectively up to 1 year and 3 months. Lower age and education were mostly associated with smoking by 6 weeks. First parity and having a nonsmoking partner were associated with abstinence up to 2 years. Interventions promoting breast feeding to incentivize continued smoking abstinence may be effective prior to weaning. Those promoting breast feeding longer than 6 months and partner smoking cessation may increase rates of long-term smoking abstinence lasting longer than 2 years postdelivery. Most mothers who quit smoking during pregnancy relapse within 6 months of delivery. Though interventions targeting new mothers have been largely unsuccessful, relapse is often delayed until after weaning and targeted breast

Relapse Analysis of Irradiated Patients Within the HD15 Trial of the German Hodgkin Study Group

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

Kriz, Jan; Reinartz, Gabriele; Dietlein, Markus

2015-05-01

Purpose: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. Methods and Materials: All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluatedmore » all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. Results: A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. Conclusions: The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses.« less

Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention.

PubMed

Witkiewitz, Katie; Lustyk, M Kathleen B; Bowen, Sarah

2013-06-01

Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse. 2013 APA, all rights reserved

Smoking Cessation and Relapse Prevention among Undergraduate Students: A Pilot Demonstration Project.

ERIC Educational Resources Information Center

Ramsay, Jim; Hoffmann, Anne

2004-01-01

The prevalence of college students' tobacco use is widely recognized, but successful cessation and relapse-prevention programs for these smokers have drawn little attention. The authors, who explored the feasibility of training peers to lead cessation and relapse-prevention programs for undergraduates, found a quit rate of 88.2%, suggesting that…

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

Towards an understanding of the biology and targeted treatment of paediatric relapsed acute lymphoblastic leukaemia.

PubMed

Irving, Julie A E

2016-03-01

Acute lymphoblastic leukaemia is the most common childhood cancer and for those children who relapse, prognosis is poor and new therapeutic strategies are needed. Recurrent pathways implicated in relapse include RAS, JAK STAT, cell cycle, epigenetic regulation, B cell development, glucocorticoid response, nucleotide metabolism and DNA repair. Targeting these pathways is a rational therapeutic strategy and may deliver novel, targeted therapies into the clinic. Relapse often stems from a minor clone present at diagnosis and thus analysis of persisting leukaemia during upfront therapy may allow targeted drug intervention to prevent relapse. © 2015 John Wiley & Sons Ltd.

[Attributable risk of co-morbid substance use disorder in poor observance to pharmacological treatment and the occurrence of relapse in schizophrenia].

PubMed

Ameller, A; Gorwood, P

2015-04-01

relapse associated with the presence of substance use disorders. The corresponding odds-ratio is 1.52 [1.19-1.94], and the attributable risk is 31.20%, but the search for biases could not be performed because of the small number of studies. These results shed light on the importance of comorbid substance use disorder to explain the poor observance frequently observed in patients with schizophrenia. Indeed, having an associated substance use disorder double the risk of poor compliance to pharmacological treatment, this comorbidity explaining a fifth of all factors involved. Although the number of available studies does not allow definite conclusions, the meta-analysis of prospective studies focusing this time of the risk of relapse requiring hospitalization is also in favor of a significant role of associated substance use disorder. These results argue in favor of developing specific strategies to better treat patients with dual diagnoses, i.e. schizophrenia and substance use disorder. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

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

Chronic relapsing pancreatitis from a scorpion sting in Trinidad.

PubMed

George Angus, L D; Salzman, S; Fritz, K; Ramirez, J; Yaman, M; Gintautas, J

1995-12-01

Chronic relapsing pancreatitis is a rare cause of abdominal pain in children and exceptionally rarely is related to a scorpion sting. We describe a 13-year-old girl who, following envenoming by a scorpion, developed recurrent attacks of sharp, intermittent pain in the umbilical region associated with fever, nausea, anorexia and vomiting, and changes in her psychological behaviour. Thorough clinical evaluation, including CT scanning, disclosed unabated pancreatitis. A modified Puestow procedure was performed with very good results. Physicians should be aware that in chronic relapsing pancreatitis, particularly in children, a scorpion sting should be considered an aetiological possibility.

Vincristine and irinotecan in children with relapsed hepatoblastoma: a single-institution experience.

PubMed

Zhang, Yu-tong; Feng, Li-hua; Zhong, Xiao-dan; Wang, Li-zhe; Chang, Jian

2015-02-01

This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB). A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS). Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively. The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.

Subacute sclerosing panencephalitis. Changes on CT scan during acute relapse.

PubMed

Modi, G; Campbell, H; Bill, P

1989-01-01

A 19-year-old female patient presented in an acute state of akinetic mutism. Serological analysis of serum and cerebrospinal fluid demonstrated the presence of antibodies to measles virus. CT scan carried out during this acute phase of relapse demonstrated white matter enhancement affecting the cortical white matter of the frontal lobes and corpus callosum. These features indicate that active demyelination occurs during acute relapse in subacute sclerosing panencephalitis (SSPE) and suggest that immunotherapy should be considered during this acute phase.

Is the Construct of Relapse Heuristic, and Does It Advance Alcohol Use Disorder Clinical Practice?

PubMed Central

Maisto, Stephen A.; Witkiewitz, Katie; Moskal, Dezarie; Wilson, Adam D.

2016-01-01

Objective: Alcohol use disorder (AUD) relapse is a construct that has been of major clinical and research interest but has been inconsistently defined. The purpose of this study was to review the definitions of AUD relapse that have been used in clinical research as a basis for drawing conclusions about its heuristic value. Method: A systematic review of the literature was conducted on empirical studies that (a) were published in peer-reviewed journals, (b) were published between 2010 and 2015, (c) were written in English, and (d) provided a definition of alcohol relapse (or lapse) that was used in the study. Results: The review yielded 139 individual studies that met inclusion criteria. The studies showed wide variability in how relapse was defined and interpreted in the literature, and there was little direct empirical or theoretical rationale provided for the definitions of relapse that were chosen. Furthermore, the concept of AUD relapse as a discrete state is not consistent with the empirical literature on the clinical course of alcohol consumption. Conclusions: We conclude that the heuristic value of AUD relapse as currently studied is low. An alternative approach that embeds the construct in theory and data on the clinical course of alcohol consumption and aligns with current trends in healthcare would seem to have a better chance of improving AUD clinical decision-making and knowledge about AUD in general. PMID:27797685

Is the Construct of Relapse Heuristic, and Does It Advance Alcohol Use Disorder Clinical Practice?

PubMed

Maisto, Stephen A; Witkiewitz, Katie; Moskal, Dezarie; Wilson, Adam D

2016-11-01

Alcohol use disorder (AUD) relapse is a construct that has been of major clinical and research interest but has been inconsistently defined. The purpose of this study was to review the definitions of AUD relapse that have been used in clinical research as a basis for drawing conclusions about its heuristic value. A systematic review of the literature was conducted on empirical studies that (a) were published in peer-reviewed journals, (b) were published between 2010 and 2015, (c) were written in English, and (d) provided a definition of alcohol relapse (or lapse) that was used in the study. The review yielded 139 individual studies that met inclusion criteria. The studies showed wide variability in how relapse was defined and interpreted in the literature, and there was little direct empirical or theoretical rationale provided for the definitions of relapse that were chosen. Furthermore, the concept of AUD relapse as a discrete state is not consistent with the empirical literature on the clinical course of alcohol consumption. We conclude that the heuristic value of AUD relapse as currently studied is low. An alternative approach that embeds the construct in theory and data on the clinical course of alcohol consumption and aligns with current trends in healthcare would seem to have a better chance of improving AUD clinical decision-making and knowledge about AUD in general.

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.

PubMed

Kumar, Shaji; Kaufman, Jonathan L; Gasparetto, Cristina; Mikhael, Joseph; Vij, Ravi; Pegourie, Brigitte; Benboubker, Lofti; Facon, Thierry; Amiot, Martine; Moreau, Philippe; Punnoose, Elizabeth A; Alzate, Stefanie; Dunbar, Martin; Xu, Tu; Agarwal, Suresh K; Enschede, Sari Heitner; Leverson, Joel D; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Touzeau, Cyrille

2017-11-30

Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X L and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added on progression during treatment. Sixty-six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion). Patients received a median of 5 prior therapies (range, 1-15); 61% were bortezomib and lenalidomide double refractory, and 46% had t(11;14). Venetoclax was generally well tolerated. Most common adverse events included mild gastrointestinal symptoms (nausea [47%], diarrhea [36%], vomiting [21%]). Cytopenias were the most common grade 3/4 events, with thrombocytopenia (32%), neutropenia (27%), anemia (23%), and leukopenia (23%) reported. The overall response rate (ORR) was 21% (14/66), and 15% achieved very good partial response or better (≥VGPR). Most responses (12/14 [86%]) were reported in patients with t(11;14). In this group, ORR was 40%, with 27% of patients achieving ≥VGPR. Biomarker analysis confirmed that response to venetoclax correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile and evidence of single-agent antimyeloma activity in patients with relapsed/refractory MM, predominantly in patients with t(11;14) abnormality and those with a favorable BCL2 family profile. Registered at www.clinicaltrials.gov: #NCT01794520. © 2017 by The American Society of Hematology.

A Typology of Relapse Promoting Situations.

ERIC Educational Resources Information Center

Shiffman, Saul

Outcome data on smoking cessation has emphasized that most people have difficulty not in quitting smoking, but in maintaining cessation. An attempt was made to develop a more meaningful typology of relapse-promoting situations using a sample of 183 exsmokers who called a telephone hotline seeking help to stay away from cigarettes. Two higher order…

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

PubMed Central

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-01-01

Background Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. Design and Methods This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1–4, prednisone at a dose of 1.5 mg/kg also on days 1–4 and thalidomide at a dose of 50–100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1–4 and 1.6, 3.2, or 4.8 g on days 5–35. Results Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3–4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. Conclusions This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1–4 followed by 4.8 g p.o. on days 5–35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs (ClinicalTrials.gov Identifier: NCT00406978). PMID:20053869

Risk of relapse after natalizumab withdrawal

PubMed Central

Vukusic, Sandra; Casey, Romain; Debard, Nadine; Stankoff, Bruno; Mrejen, Serge; Uhry, Zoe; Van Ganse, Eric; Castot, Anne; Clanet, Michel; Lubetzki, Catherine; Confavreux, Christian

2016-01-01

Objective: To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort. Methods: In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model. Results: Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41–0.49). Conclusions: This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings. PMID:27844037

Socio-economic correlates of relapsed patients admitted in a Nigerian mental health institution.

PubMed

Gbiri, Caleb A; Badru, Fatai A; Ladapo, Harry T O; Gbiri, Adefolakemi A

2011-03-01

Relapse in psychiatric disorders is highly distressing, costly and engenders burn-out syndrome among mental-health workers. To study the socio-economic factors associated with relapse in individual admitted with psychiatric disorders and the pattern of socio-economic impact of relapse in those groups. A cross-sectional survey of all relapsed patients without cognitive deficit admitted into the federal Neuro-Psychiatric Hospital, Lagos, Nigeria between June and October 2007 was conducted using a self-validated Structured Interview Schedule (Relapse Socio-economic Impact Interview Schedule) and Key Informant Interview Guide. Secondary data were elicited from the patient folders, case notes, ward admission registers and nominal rolls. Data were summarised using mean, standard deviation, frequency and percentiles. Pearson's moment correlation coefficient was used to test the association among variables. The Mann-Whitney U-test was used to compare the pre-morbid and the post-morbid states. This study involved 102 respondents. Their mean age was 36.5 ± 9.8 years, mainly of male gender (72.5%) suffering from schizophrenic disorder (37.8%). Relapse and re-admission ranged between 2 and 12. Unemployment rate, marital separation and divorce increased more than 5-fold from pre-morbid to morbid states. Few (4.9%) could still settle their hospital/drug bills on their own, while most (95.1%) depended on family, philanthropist and government/waivers to pay for their bills. Their social relationships were negatively influenced with most of them expressing social isolation and low quality of life. There were significant relationships (P<0.05) between age, sex, number of relapses, number of admissions, pre-morbid marital status, morbid state marital status, pre-morbid state occupational status and morbid state occupational status. There was significant change (P= 0.00) in the quality of life, societal integration/acceptability, economic status, employment status and marital status

Treating Multiply Relapsed or Refractory Hairy Cell Leukemia

Cancer.gov

In this trial, patients with hairy cell leukemia who have not responded or relapsed after initial chemotherapy will be randomly assigned to receive rituximab combined with either pentostatin or bendamustine.

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.

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

PubMed Central

Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

2015-01-01

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

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

Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.

PubMed

Stone, Lael Anne; Cutter, Gary Raymond; Fisher, Elizabeth; Richert, Nancy; McCartin, Jennifer; Ohayon, Joan; Bash, Craig; McFarland, Henry

2016-05-01

Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years. Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated. While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS. While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that 1 route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted. Copyright © 2015 by the American Society of Neuroimaging.

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.

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.

Depletion of CD20 B cells fails to inhibit relapsing mouse experimental autoimmune encephalomyelitis.

PubMed

Sefia, Eseberuo; Pryce, Gareth; Meier, Ute-Christiane; Giovannoni, Gavin; Baker, David

2017-05-01

Multiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease. This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. However, CD4-depletion using a monoclonal antibody was considered unsuccessful and relapsing MS responds well to B cell depletion via CD20 B cell depleting antibodies. The influence of CD20 B cell depletion in relapsing EAE was assessed. Relapsing EAE was induced in Biozzi ABH mice. These were treated with CD20-specific (18B12) antibody and the influence on CD45RA-B220 B cell depletion and clinical course was analysed. Relapsing EAE in Biozzi ABH failed to respond to the marked B cell depletion induced with a CD20-specific antibody. In contrast to CD20 and CD8-specific antibodies, CD4 T cell depletion inhibited EAE. Spinal cord antigen-induced disease in ABH mice is CD4 T cell-dependent. The lack of influence of CD20 B cell depletion in relapsing EAE, coupled with the relatively marginal and inconsistent results obtained in other mouse studies, suggests that rodents may have limited value in understanding the mechanism occurring following CD20 B cell depletion in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Effectiveness of complex psycho-educational interventions for smoking relapse prevention: an exploratory meta-analysis.

PubMed

Song, Fujian; Huttunen-Lenz, Maija; Holland, Richard

2010-09-01

Existing systematic reviews have concluded that psycho-educational interventions for smoking relapse prevention were ineffective. Our objective was to conduct an exploratory meta-analysis, guided by mechanisms of these complex interventions for preventing smoking relapse. Relevant trials were identified from a Cochrane review and by an updated search of MEDLINE and PsycINFO (up to August 2009). We examined theories or mechanisms underlying relapse prevention interventions, and process variables reported in trials. Odds ratios (ORs) for the rate of smoking abstinence at the longest follow-up were pooled in meta-analysis. Forty-nine trials were included, and interventions were at least partly based on the cognitive-behavioural approach to coping skills training in 41 trials. Only a few trials reported data on process variables. Coping skills training for smoking relapse prevention was effective for community quitters (OR 1.27, 95% CI: 1.08-1.49), and particularly for those who stopped smoking for at least 1 week at baseline (OR 1.52, 95% CI: 1.20-1.93). These findings were interpretable with mechanisms of coping skills training for relapse prevention. On the basis of post hoc subgroup analyses, coping skills training for smoking relapse prevention is effective for motivated community quitters. This finding has important public health implications and needs to be confirmed by further trials.

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.

Promising reciprocity: When proposing a favor for a request increases compliance even if the favor is not accepted.

PubMed

Guéguen, Nicolas; Meineri, Sébastien; Ruiz, Clément; Pascual, Alexandre

2016-01-01

Research has reported that reciprocity is an important social norm in relationships. In previous studies on reciprocity, participants' behavior was examined after receiving a favor from someone. In a series of field studies, we examined the effect of a statement that proved that a solicitor was someone who respected this principle. Confederates solicited participants for money or a cigarette in exchange for stamps or money, respectively. It was found that the participants complied more readily with the request in the promised favor condition, but most of them refused to take the promised favor. We conclude that individuals were led to help those who respected the putative norm of reciprocity in their social interaction.

Saccharomyces boulardii does not prevent relapse of Crohn's disease.

PubMed

Bourreille, Arnaud; Cadiot, Guillaume; Le Dreau, Gérard; Laharie, David; Beaugerie, Laurent; Dupas, Jean-Louis; Marteau, Philippe; Rampal, Patrick; Moyse, Dominique; Saleh, Ashraf; Le Guern, Marie-Emmanuelle; Galmiche, Jean-Paul

2013-08-01

Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points. CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation. Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lifestyle-related disease in Crohn’s disease: Relapse prevention by a semi-vegetarian diet

PubMed Central

Chiba, Mitsuro; Abe, Toru; Tsuda, Hidehiko; Sugawara, Takeshi; Tsuda, Satoko; Tozawa, Haruhiko; Fujiwara, Katsuhiko; Imai, Hideo

2010-01-01

AIM: To investigate whether semi-vegetarian diet (SVD) has a preventive effect against relapse of Crohn’s disease (CD) in patients who have achieved remission, who are a high-risk group for relapse. METHODS: A prospective, single center, 2-year clinical trial was conducted. Twenty-two adult CD patients who achieved clinical remission either medically (n = 17) or surgically (n = 5) and consumed an SVD during hospitalization were advised to continue with an SVD and avoid known high-risk foods for inflammatory bowel disease. The primary endpoint was clinical relapse defined as the appearance of active symptoms of CD. Kaplan-Meier survival analysis was used to calculate the cumulative proportion of patients who had a relapse. A 2-year analysis of relapse rates of patients who followed an SVD and those who did not (an omnivorous diet group) was undertaken. RESULTS: SVD was continued by 16 patients (compliance 73%). Remission was maintained in 15 of 16 patients (94%) in the SVD group vs two of six (33%) in the omnivorous group. Remission rate with SVD was 100% at 1 year and 92% at 2 years. SVD showed significant prevention in the time to relapse compared to that in the omnivorous group (P = 0.0003, log rank test). The concentration of C-reactive protein was normal at the final visit in more than half of the patients in remission who were taking an SVD, who maintained remission during the study (9/15; 60%), who terminated follow-up (8/12; 67%), and who completed 2 years follow-up (7/10; 70%). There was no untoward effect of SVD. CONCLUSION: SVD was highly effective in preventing relapse in CD. PMID:20503448

Role of Endotoxin in the Pathogenesis of Louse-borne Relapsing Fever and in the Mechanism of the Jarisch-Herxheimer Reaction Following Treatment of Louse-borne Relapsing Fever

DTIC Science & Technology

1977-12-01

therapy and during the Jarisch-Herxheimer-like reaction. Further similarities between relapsing fever and Gram-negative bacteremic diseases were sought by...activated during Gram- negative bacterial infections (11-17). The aims of therapy should be to clear the blood of circulating spirochetes without relapse and...more slowly with more prolonged fever. Single dose therapy with intravenous tetracycline [1,2] and oral doxycycline [18] has been shown effective, but

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

Gastritis: the histology report.

PubMed

Rugge, Massimo; Pennelli, Gianmaria; Pilozzi, Emanuela; Fassan, Matteo; Ingravallo, Giuseppe; Russo, Valentina M; Di Mario, Francesco

2011-03-01

Gastritis is defined as inflammation of the gastric mucosa. In histological terms, it is distinguishable into two main categories, i.e. non-atrophic and atrophic. In the gastric mucosa, atrophy is defined as the loss of appropriate glands. There are several etiological types of gastritis, their different etiology being related to different clinical manifestations and pathological features. Atrophic gastritis (resulting mainly from long-standing Helicobacter pylori infection) is a major risk factor for the onset of (intestinal type) gastric cancer. The extent and site of the atrophic changes correlate significantly with the cancer risk. The current format for histology reporting in cases of gastritis fails to establish an immediate link between gastritis phenotype and risk of malignancy. Building on current knowledge of the biology of gastritis, an international group of pathologists [Operative Link for Gastritis Assessment (OLGA)] has proposed a system for reporting gastritis in terms of its stage (the OLGA Staging System): this system places the histological phenotypes of gastritis on a scale of progressively increasing gastric cancer risk, from the lowest (Stage 0) to the highest (Stage IV). The aim of this tutorial is to provide unequivocal information on how to standardize histology reports on gastritis in diagnostic practice. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Natural killer cell therapy in children with relapsed leukemia.

PubMed

Rubnitz, Jeffrey E; Inaba, Hiroto; Kang, Guolian; Gan, Kwan; Hartford, Christine; Triplett, Brandon M; Dallas, Mari; Shook, David; Gruber, Tanja; Pui, Ching-Hon; Leung, Wing

2015-08-01

Novel therapies are needed for children with relapsed or refractory leukemia. We therefore tested the safety and feasibility of haploidentical natural killer cell therapy in this patient population. Twenty-nine children who had relapsed or refractory leukemia were treated with chemotherapy followed by the infusion of haploidentical NK cells. Cohort 1 included 14 children who had not undergone prior allogeneic hematopoietic cell transplantation (HCT), whereas Cohort 2 included 15 children with leukemia that had relapsed after HCT. Twenty-six (90%) NK donors were KIR mismatched (14 with one KIR and 12 with 2 KIRs). The peak NK chimerism levels were >10% donor in 87% of the evaluable recipients. In Cohort 1, 10 had responsive disease and 12 proceeded to HCT thereafter. Currently, 5 (36%) are alive without leukemia. In Cohort 2, 10 had responsive disease after NK therapy and successfully proceeded to second HCT. At present, 4 (27%) are alive and leukemia-free. The NK cell infusions and the IL-2 injections were well-tolerated. NK cell therapy is safe, feasible, and should be further investigated in patients with chemotherapy-resistant leukemia. © 2015 Wiley Periodicals, Inc.

Comprehensive histological evaluation of bone implants

PubMed Central

Rentsch, Claudia; Schneiders, Wolfgang; Manthey, Suzanne; Rentsch, Barbe; Rammelt, Stephan

2014-01-01

To investigate and assess bone regeneration in sheep in combination with new implant materials classical histological staining methods as well as immunohistochemistry may provide additional information to standard radiographs or computer tomography. Available published data of bone defect regenerations in sheep often present none or sparely labeled histological images. Repeatedly, the exact location of the sample remains unclear, detail enlargements are missing and the labeling of different tissues or cells is absent. The aim of this article is to present an overview of sample preparation, staining methods and their benefits as well as a detailed histological description of bone regeneration in the sheep tibia. General histological staining methods like hematoxylin and eosin, Masson-Goldner trichrome, Movat’s pentachrome and alcian blue were used to define new bone formation within a sheep tibia critical size defect containing a polycaprolactone-co-lactide (PCL) scaffold implanted for 3 months (n = 4). Special attention was drawn to describe the bone healing patterns down to cell level. Additionally one histological quantification method and immunohistochemical staining methods are described. PMID:24504113

Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate.

PubMed

Foster, C Stephen; Tufail, Fehma; Waheed, Nadia Khalida; Chu, David; Miserocchi, Elisabetta; Baltatzis, Stefanos; Vredeveld, Cindy M

2003-04-01

To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Patients with chronic or recurrent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate.

Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS.

PubMed

Kneider, M; Bergström, T; Gustafsson, C; Nenonen, N; Ahlgren, C; Nilsson, S; Andersen, O

2009-04-01

Upper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported. To evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant. Nasopharyngeal fluid was aspirated from 36 multiple sclerosis patients at pre-defined critical time points. Reverse-transcriptase-PCR was performed to detect human rhinovirus-RNA. Positive amplicons were sequenced. We found that rhinovirus RNA was present in 17/40 (43%) of specimens obtained at the onset of a URTI in 19 patients, in 1/21 specimens during convalescence after URTI in 14 patients, in 0/6 specimens obtained in 5 patients on average a week after the onset of an "at risk" relapse, occurring within a window in time from one week before to three weeks after an infection, and in 0/17 specimens obtained after the onset of a "not at risk" relapse not associated with any infection in 12 patients. Fifteen specimens from healthy control persons not associated with URTI were negative. The frequency of HRV presence in URTI was similar to that reported for community infections. Eight amplicons from patients represented 5 different HRV strains. We were unable to reproduce previous findings of association between HRV infections and multiple sclerosis relapses. HRV was not present in nasopharyngeal aspirates obtained during "at risk" or "not at risk" relapses. Sequencing of HRV obtained from patients during URTI did not reveal any strain with predominance in multiple sclerosis.

Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

PubMed Central

Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

2010-01-01

Objective We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy (CBT) to prevent relapse in youths with major depressive disorder (MDD) who have responded to acute phase pharmacotherapy. Method Forty-six youths (ages 11–18 years) who had responded to 12 weeks of treatment with fluoxetine were randomized to receive either 6 months of continued antidepressant medication management (MM) or antidepressant MM plus relapse prevention CBT (MM+CBT). Primary outcome was time to relapse, defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse. Results Cox proportional hazards regression, adjusting for depression severity at randomization and for the hazard of relapsing by age across the trial, revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group (hazard ratio = 8.80; 95% confidence interval 1.01–76.89; χ2 = 3.86, p = .049) during 6 months of continuation treatment. In addition, patient satisfaction was significantly higher in the MM+CBT group. No differences were found between the two treatment groups on attrition rate, serious adverse events, and overall global functioning. Conclusions These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase. PMID:18978634

Controversies in autologous and allogeneic hematopoietic cell transplantation in peripheral T/NK-cell lymphomas.

PubMed

Shustov, Andrei

2013-03-01

Peripheral T-cell and NK-cell lymphomas (PT/NKCL) are a heterogeneous group of lymphoid neoplasms with poor outcomes. There is no consensus on the best front line therapy or management of relapsed/refractory disease. The use of autologous and allogeneic hematopoietic cell transplantation (HCT) has been studied in both settings to improve outcomes. Multiple retrospective and several prospective trials were reported. While at first sight the outcomes in the relapsed/refractory setting appear similar in B-cell and T-cell lymphomas when treated with high dose therapy (HDT) and autologous HCT, it is becoming obvious that only specific subtypes of PTCL benefit from this approach (i.e. anaplastic large cell lymphoma [ALCL] and angioimmunoblastic lymphoma [AITL] in second CR). In less favorable histologies, HDT seems to provide limited benefit, with the majority of patients experiencing post-transplant relapse. The use of autologous HCT to consolidate first remission has been evaluated in several prospective trials. Again, the best results were observed in ALCL, but the superiority of this approach over chemotherapy alone needs confirmation in randomized trials. In less favorable histologies, high-dose consolidation resulted in low survival rates comparable to those obtained with chemotherapy alone, and without randomized trials it is hard to recommend this strategy to all patients with newly diagnosed PT/NKCL. Allogeneic HCT might provide potent and potentially curative graft-vs-lymphoma effect and overcome chemotherapy resistance. Only a few studies have been reported to date on allogeneic HCT in PT/NKCL. Based on available data, eligible patients benefit significantly from this approach, with 50% or more patients achieving long-term disease control or cure, although at the expense of significant treatment related mortality (TRM). Reduced-intensity conditioning regimens appear to have lower TRM and might extend this approach to older patients. With the recent approval of

Positive impact of integrating histology and physiology teaching at a medical school in China.

PubMed

Sherer, Renslow; Wan, Yu; Dong, Hongmei; Cooper, Brian; Morgan, Ivy; Peng, Biwen; Liu, Jun; Wang, Lin; Xu, David

2014-12-01

To modernize its stagnant, traditional curriculum and pedagogy, the Medical School of Wuhan University in China adopted (with modifications) the University of Chicago's medical curriculum model. The reform effort in basic sciences was integrating histology and physiology into one course, increasing the two subjects' connection to clinical medicine, and applying new pedagogies and assessment methods. This study assessed the results of the reform by comparing the attitudes and academic achievements of students in the reform curriculum (n = 41) and their traditional curriculum peers (n = 182). An attitude survey was conducted to obtain students' views of their respective histology and physiology instruction. Survey items covered lectures, laboratory teaching, case analyses and small-group case discussions, assessment of students, and overall quality of the courses and instruction. A knowledge test consisting of questions from three sources was given to measure students' mastery of topics that they had learned. Results showed that reform curriculum students were rather satisfied with their course and new teaching methods in most cases. When these students' attitudes were compared with those of their traditional curriculum peers, several significant differences favoring the reform were identified regarding physiology teaching. No other significant difference was found for physiology or histology teaching. Reform curriculum students outperformed their peers on four of five subcategories of the knowledge test questions. These findings support the benefits of integration and state-of-the-art teaching methods. Our study may offer lessons to medical schools in China and other countries whose medical education is in need of change. Copyright © 2014 The American Physiological Society.

Multi-modal image registration: matching MRI with histology

NASA Astrophysics Data System (ADS)

Alic, Lejla; Haeck, Joost C.; Klein, Stefan; Bol, Karin; van Tiel, Sandra T.; Wielopolski, Piotr A.; Bijster, Magda; Niessen, Wiro J.; Bernsen, Monique; Veenland, Jifke F.; de Jong, Marion

2010-03-01

Spatial correspondence between histology and multi sequence MRI can provide information about the capabilities of non-invasive imaging to characterize cancerous tissue. However, shrinkage and deformation occurring during the excision of the tumor and the histological processing complicate the co registration of MR images with histological sections. This work proposes a methodology to establish a detailed 3D relation between histology sections and in vivo MRI tumor data. The key features of the methodology are a very dense histological sampling (up to 100 histology slices per tumor), mutual information based non-rigid B-spline registration, the utilization of the whole 3D data sets, and the exploitation of an intermediate ex vivo MRI. In this proof of concept paper, the methodology was applied to one tumor. We found that, after registration, the visual alignment of tumor borders and internal structures was fairly accurate. Utilizing the intermediate ex vivo MRI, it was possible to account for changes caused by the excision of the tumor: we observed a tumor expansion of 20%. Also the effects of fixation, dehydration and histological sectioning could be determined: 26% shrinkage of the tumor was found. The annotation of viable tissue, performed in histology and transformed to the in vivo MRI, matched clearly with high intensity regions in MRI. With this methodology, histological annotation can be directly related to the corresponding in vivo MRI. This is a vital step for the evaluation of the feasibility of multi-spectral MRI to depict histological groundtruth.

Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost.

PubMed

Mortimer, A; Williams, P; Meddis, D

2003-01-01

Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

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

PubMed

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

2012-10-01

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

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..

The value of nodal information in predicting lung cancer relapse using 4DPET/4DCT

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

Li, Heyse, E-mail: heyse.li@mail.utoronto.ca; Becker, Nathan; Raman, Srinivas

2015-08-15

Purpose: There is evidence that computed tomography (CT) and positron emission tomography (PET) imaging metrics are prognostic and predictive in nonsmall cell lung cancer (NSCLC) treatment outcomes. However, few studies have explored the use of standardized uptake value (SUV)-based image features of nodal regions as predictive features. The authors investigated and compared the use of tumor and node image features extracted from the radiotherapy target volumes to predict relapse in a cohort of NSCLC patients undergoing chemoradiation treatment. Methods: A prospective cohort of 25 patients with locally advanced NSCLC underwent 4DPET/4DCT imaging for radiation planning. Thirty-seven image features were derivedmore » from the CT-defined volumes and SUVs of the PET image from both the tumor and nodal target regions. The machine learning methods of logistic regression and repeated stratified five-fold cross-validation (CV) were used to predict local and overall relapses in 2 yr. The authors used well-known feature selection methods (Spearman’s rank correlation, recursive feature elimination) within each fold of CV. Classifiers were ranked on their Matthew’s correlation coefficient (MCC) after CV. Area under the curve, sensitivity, and specificity values are also presented. Results: For predicting local relapse, the best classifier found had a mean MCC of 0.07 and was composed of eight tumor features. For predicting overall relapse, the best classifier found had a mean MCC of 0.29 and was composed of a single feature: the volume greater than 0.5 times the maximum SUV (N). Conclusions: The best classifier for predicting local relapse had only tumor features. In contrast, the best classifier for predicting overall relapse included a node feature. Overall, the methods showed that nodes add value in predicting overall relapse but not local relapse.« less

Prefrontal gamma-aminobutyric acid type A receptor insertion controls cue-induced relapse to nicotine seeking.

PubMed

Lubbers, Bart R; van Mourik, Yvar; Schetters, Dustin; Smit, August B; De Vries, Taco J; Spijker, Sabine

2014-11-01

Current smoking cessation therapies offer limited success, as relapse rates remain high. Nicotine, which is the major component of tobacco smoke, is thought to be primarily responsible for the addictive properties of tobacco. However, little is known about the molecular mechanisms underlying nicotine relapse, hampering development of more effective therapies. The objective of this study was to elucidate the role of medial prefrontal cortex (mPFC) glutamatergic and gamma-aminobutyric acid (GABA)ergic receptors in controlling relapse to nicotine seeking. Using an intravenous self-administration model, we studied glutamate and gamma-aminobutyric acid receptor regulation in the synaptic membrane fraction of the rat mPFC following extinction and cue-induced relapse to nicotine seeking. Subsequently, we locally intervened at the level of GABAergic signaling by using a mimetic peptide of the GABA receptor associated protein-interacting domain of GABA type A (GABAA) receptor subunit γ2 (TAT-GABAγ2) and muscimol, a GABAA receptor agonist. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors were not regulated after the 30-min relapse test. However, GABAA receptor subunits α1 and γ2 were upregulated, and interference with GABAA receptor insertion in the cell membrane using the TAT-GABAγ2 peptide in the dorsal mPFC, but not the ventral mPFC, significantly increased responding during relapse. Increasing GABAA transmission with muscimol in the dorsal and ventral mPFC attenuated relapse. These data indicate that cue-induced relapse entails a GABAergic plasticity mechanism that limits nicotine seeking by restoring inhibitory control in the dorsal mPFC. GABAA receptor-mediated neurotransmission in the dorsal mPFC constitutes a possible future therapeutic target for maintaining smoking abstinence. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. 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

Re-Training the Addicted Brain: A Review of Hypothesized Neurobiological Mechanisms of Mindfulness-Based Relapse Prevention

PubMed Central

Witkiewitz, Katie; Lustyk, M. Kathleen B.; Bowen, Sarah

2013-01-01

Addiction has generally been characterized as a chronic relapsing condition. Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, Mindfulness-Based Relapse Prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting “automatically.” A recent efficacy trial found that those randomized to MBRP, as compared to those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. Importantly, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive behavior relapse. PMID:22775773

Nondaily Smokers' Characteristics and Likelihood of Prenatal Cessation and Postpartum Relapse.

PubMed

Rockhill, Karilynn M; Tong, Van T; England, Lucinda J; D'Angelo, Denise V

2017-07-01

This study aimed to calculate the prevalence of pre-pregnancy nondaily smoking (<1 cigarette/day), risk factors, and report of prenatal provider smoking education; and assess the likelihood of prenatal cessation and postpartum relapse for nondaily smokers. We analyzed data from 2009 to 2011 among women with live-born infants participating in the Pregnancy Risk Assessment Monitoring System. We compared characteristics of pre-pregnancy daily smokers (≥1 cigarette/day), nondaily smokers, and nonsmokers (chi-square adjusted p < .025). Between nondaily and daily smokers, we compared proportions of prenatal cessation, postpartum relapse (average 4 months postpartum), and reported provider education. Multivariable logistic regression calculated adjusted prevalence ratios (APR) for prenatal cessation among pre-pregnancy smokers (n = 27 360) and postpartum relapse among quitters (n = 13 577). Nondaily smokers (11% of smokers) were more similar to nonsmokers and differed from daily smokers on characteristics examined (p ≤ .001 for all). Fewer nondaily smokers reported provider education than daily smokers (71.1%, 86.3%; p < .001). A higher proportion of nondaily compared to daily smokers quit during pregnancy (89.7%, 49.0%; p < .001), and a lower proportion relapsed postpartum (22.2%, 48.6%; p < .001). After adjustment, nondaily compared to daily smokers were more likely to quit (APR: 1.65; 95% confidence interval [CI]: 1.58-1.71) and less likely to relapse postpartum (APR: 0.55; 95% CI: 0.48-0.62). Nondaily smokers were more likely to quit smoking during pregnancy, less likely to relapse postpartum, and less likely to report provider education than daily smokers. Providers should educate all women, regardless of frequency of use, about the harms of tobacco during pregnancy, provide effective cessation interventions, and encourage women to be tobacco free postpartum and beyond. Nondaily smoking (<1 cigarette/day) is increasing among US smokers and carries a significant

Resistance to Change and Relapse of Observing

ERIC Educational Resources Information Center

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…

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE PAGES

Yates, Lucy R.; Knappskog, Stian; Wedge, David; ...

2017-08-14

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Genomic Evolution of Breast Cancer Metastasis and Relapse

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

Yates, Lucy R.; Knappskog, Stian; Wedge, David

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Received View of Addiction, Relapse and Treatment.

PubMed

Ndasauka, Yamikani; Wei, Zhengde; Zhang, Xiaochu

2017-01-01

It is important to highlight that attempts at understanding and explaining addiction have been made for centuries. It is, however, just five decades ago, with the growth of science and technology that more interest has been observed in this field. This chapter examines different views and theories that have been posited to understand and explain addiction. More attention will be given to prominent views that seem to draw consensus among researchers and medical practitioners. The first section of the chapter introduces the addiction debate, the different theories that have been provided to explain it from different perspectives and disciplines such as neurosciences, philosophy and psychology. Then, the chapter discusses different views on the role of relapse and what it entails in understanding addiction. The second section discusses different proposed and used forms of treating addiction. Thus, the chapter discusses the received view of addiction, the understanding of relapse as a critical element in addiction and treatments.

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

PubMed

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

2017-04-02

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

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

PubMed

Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

2017-11-15

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non

Modeling the Complexity of Post-Treatment Drinking: It’s a Rocky Road to Relapse

PubMed Central

Witkiewitz, Katie; Marlatt, G. Alan

2007-01-01

The most widely cited road block to successful treatment outcomes for psychological and substance use disorders has been described as the return to the previous behavior, or “relapse.” The operational definition of “relapse” varies from study to study and between clinicians, but in general the term is used to indicate the return to previous levels of symptomatic behavior. One explanation for the variation in the operationalization of relapse is the wide variety of behaviors for which the term is applied, including (but not limited to): depression, substance abuse, schizophrenia, mania, sexual offending, risky sexual behavior, dieting, and the anxiety disorders. A second explanation for the multitude of definitions for relapse is the inherent complexity in the process of behavior change. In this paper we present the most recent treatment outcome research evaluating relapse rates, with a special focus on the substance use disorders. Following this review of the literature we present an argument for the operationalization of relapse as a dynamic process, which can be empirically characterized using dynamical systems theory. We support this argument by presenting results from the analysis of alcohol treatment outcomes using catastrophe modeling techniques. These results demonstrate the utility of catastrophe theory in modeling the alcohol relapse process. The implications of these analyses for the treatment of alcohol use disorders, as well as a discussion of future research incorporating nonlinear dynamical systems theory is provided. PMID:17355897

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.

Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

PubMed

Havermans, Remco C; Jansen, Anita T M

2003-07-01

Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

[Mindfulness-based-relapse prevention (MBRP): Evaluation of the impact of a group of Mindfulness Therapy in alcohol relapse prevention for alcohol use disorders].

PubMed

Carpentier, D; Romo, L; Bouthillon-Heitzmann, P; Limosin, F

2015-12-01

For several years, the learning of mindfulness has developed in a psychological intervention perspective, particularly in the field of addiction. Presently, the management of addictions with substances is centered on two questions: the motivation in the change of behaviour and in a significant change in alcohol consumption. Concerning alcohol dependence, the evolution of behaviour is variable and characterized by forgiveness episodes and relapses. Over many years, a treatment for the abuse of substance associated with techniques based on full consciousness (Kabat-Zinn, 1990; Segal et al., 2002) Mindfulness-based relapse prevention (MBRP) was developed by Marlatt et al. (2011). The prevention of the relapse therapy, based on full consciousness, is a program of eight sessions integrating techniques of "mindfulness" into the techniques of prevention of the relapse. However, not much research has focused on the MBRP, the publication of the manual regarding this intervention is too recent (Bowen S et al., 2011). We are interested in the active mechanisms, which are at stake in the MBRP. Indeed, the meditation acts presents many mechanisms in the addicting disorders. Our non-controlled research was based on a protocol in order to evaluate the alcohol consummation, mindfulness, impulsiveness, automatic thoughts, anxiety and abilities to cope. The first results are interesting: reduction of alcohol consummation, increase of mindfulness, reduction of trigger relapse, increasing cognitive flexibility and high degree of satisfaction among participants. An intervention MBRP was proposed to 26 patients who were assigned to three groups. They were questioned about their alcohol consumption and assessed by a protocol of seven evaluations before and after the group MBRP: Five Facets Mindfulness (FFMQ), Impulsive Behavior Scale (UPPS), Acceptance and Action Questionnaire (AAQ II), State Trait Anxiety Inventory (STAI-A, STAI-B), Questionnaire of the automatic thoughts (QPA), and

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.

Relapse revisited: a critique of current concepts and clinical practice in the management of alcohol problems.

PubMed

Saunders, B; Houghton, M

1996-01-01

How a problem is understood dictates how it is responded to. In this paper the problem of relapse and alcohol dependence is reconsidered. The existing major relapse paradigm is evaluated against the last two decades of research. It is concluded that the available research strongly questions the notion that relapse is an addiction-specific event. Instead, relapse is probably better understood as a complex, generic, human behaviour, undertaken at times by all of us. Given this, it is possible that mainstream psychological theories, such as decision making and attribution theory, are important in coming to any understanding of the phenomenon of relapse. It is also contended that the investigation of relapse is potentially an error of focus. Such study invites the investigation of those who do not succeed in changing behaviour, as against the study of those who do. For those concerned with the treatment of alcohol dependence, studying the successes may be a more informative process than studying the putative failures. Given the burgeoning of research over the past two decades the impact on treatment practice is reviewed. It is concluded that relapse prevention and management is very much on the alcohol-intervention agenda. However, the research evidence to date is consistent with the general psychotherapy literature in that doing something appears better than no intervention, but that an optimum, effective, intervention has yet to be devised.

Enhanced gamma interferon responses of mouse spleen cells following immunotherapy for tuberculosis relapse.

PubMed

Gil, Olga; Vilaplana, Cristina; Guirado, Evelyn; Díaz, Jorge; Cáceres, Neus; Singh, Mahavir; Cardona, Pere-Joan

2008-11-01

Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells.

Rituximab for relapsing-remitting multiple sclerosis.

PubMed

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

2013-12-06

This is an update of the Cochrane review "Rituximab for relapsing-remitting multiple sclerosis" (first published in The Cochrane Library 2011, Issue 12).More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately 10 years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RRMS) convert to secondary progressive MS. MS causes a major socioeconomic burden for the individual patient and for society. Effective treatment that reduces relapse frequency and prevents progression could impact both costs and quality of life and help to reduce the socioeconomic burden of MS. Alternative and more effective MS treatments with new modes of action and good safety are needed to expand the current treatment repertoire. It has been shown that B lymphocytes are involved in the pathophysiology of MS and rituximab lyses B-cells via complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell depletion therapy in the treatment of RRMS. The safety and effectiveness of rituximab, as monotherapy or combination therapy, versus placebo or approved disease-modifying drugs (DMDs) (interferon-β (IFN-β), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab) to reduce disease activity for people with RRMS were assessed. The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register (9 August 2013). We checked the references in identified trials and manually searched the reports (2004 to August 2013) from neurological associations and MS societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec and Roche. All randomised, double-blind, controlled parallel group clinical trials with a length

[Histological investigations in ambulatory oral surgery practice].

PubMed

Kivovics, Márton; Mihályi, Szilvia; Suba, Zsuzsanna; Gyulai-Gaál, Szabolcs

2012-03-01

In the practice of oral surgery correspondence with the pathologist is required in order to identify the lesions in question by histologic examination. By current legal regulations the histological evaluation of removed tissues is mandatory. In the presentation the authors process the data obtained in their Department since 2008. Coincidence of the clinical and histological diagnosis is analysed statistically such is the occurrence of various types of oral mucosa lesions and cysts. In cases of presumed malignancy the biopsies were carried out in a department with adequate oncological background. In indications of autoimmun deseases mainly in cases of Sjögren's syndrome the Department has been requested to carry out minor salivary gland biopsies. Statistical analysis of the findings of the minor salivary gland biopsies will also be discussed. The histological diagnoses have been provided by Prof. Zsuzsanna Suba MD, DMD, PhD of the Semmelweis University, Department of Oral and Maxillofacial Surgery, Oral Pathology Unit. In order of prevalence the most common histologically verified lesions were: radicular cyst, fibromas and granulation tissue. In 84.5% of the cases the histological findings confirmed the clinical diagnoses. In 44,5% of the cases Sjögren's syndrome was verified by the minor salivary gland biopsy. Although in most cases the histological examination supported the clinical diagnoses, close cooperation of the oral surgeon and pathologist is essential.

What causes relapses of autoimmune diseases? The etiological role of autoreactive T cells.

PubMed

Wildner, Gerhild; Kaufmann, Ulrike

2013-09-01

Most human autoimmune diseases have a relapsing-remitting or a chronic progressive course, while animal models are usually acute and monophasic. In our experimental animal model the disease can be either monophasic or remitting, depending on the autoantigen used for induction, and it appears to lie in the effector phenotype of the elicited T helper cell response. Since both, monophasic and relapsing courses of disease are induced by immunization as well as by adoptive transfer of peptide-specific, CD4(+) T cells, we were able to directly compare the transcriptomes of pathogenic T cell lines by gene array analysis and qPCR as well as protein expression. Upregulated genes were only determined in T cells inducing relapsing uveitis and belong to certain pathways of antigen presentation, activation, inflammation, migration and survival, comprising WNT, Hedgehog, MAP-kinase and JAK/STAT-pathways. These pathways are partially interacting with each other, and the central molecule upregulated in T cells causing relapsing disease was found to be IFN-γ. Here the course of the autoimmune diseases strictly depends on the characteristics of the autoreactive T cells, which are already determined at their early stage of antigen-specific activation. Our rat models of experimental autoimmune uveitis could help elucidating the immune mechanisms behind relapsing autoimmunity in order to develop better therapeutic strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

19 CFR 200.735-105 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 false Gifts, entertainment, and favors. 200.735-105...-105 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, no employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan, or...

19 CFR 200.735-105 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 false Gifts, entertainment, and favors. 200.735-105...-105 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, no employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan, or...

19 CFR 200.735-105 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 false Gifts, entertainment, and favors. 200.735-105...-105 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, no employee may solicit or accept, directly or indirectly, any gift, gratuity, favor, entertainment, loan, or...

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.

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.

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

PubMed

Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

22 CFR 1203.735-305 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Gifts, entertainment, and favors. 1203.735-305....735-305 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, a..., gratuity, loan, entertainment, or favor for the employee or another person, particularly one with whom the...

22 CFR 1203.735-305 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Gifts, entertainment, and favors. 1203.735-305....735-305 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, a..., gratuity, loan, entertainment, or favor for the employee or another person, particularly one with whom the...

22 CFR 1203.735-305 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Gifts, entertainment, and favors. 1203.735-305....735-305 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, a..., gratuity, loan, entertainment, or favor for the employee or another person, particularly one with whom the...

22 CFR 1203.735-305 - Gifts, entertainment, and favors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Gifts, entertainment, and favors. 1203.735-305....735-305 Gifts, entertainment, and favors. (a) Except as provided in paragraph (b) of this section, a..., gratuity, loan, entertainment, or favor for the employee or another person, particularly one with whom the...

Cancer evolution, mutations, and clonal selection in relapse neuroblastoma.

PubMed

Schulte, Marc; Köster, Johannes; Rahmann, Sven; Schramm, Alexander

2018-05-01

The notion of cancer as a complex evolutionary system has been validated by in-depth molecular analyses of tumor progression over the last years. While a complex interplay of cell-autonomous programs and cell-cell interactions determines proliferation and differentiation during normal development, intrinsic and acquired plasticity of cancer cells allow for evasion of growth factor limitations, apoptotic signals, or attacks from the immune system. Treatment-induced molecular selection processes have been described by a number of studies already, but understanding of those events facilitating metastatic spread, organ-specific homing, and resistance to anoikis is still in its early days. In principle, somatic events giving rise to cancer progression should be easier to follow in childhood tumors bearing fewer mutations and genomic aberrations than their counterparts in adulthood. We have previously reported on the genetic events accompanying relapsing neuroblastoma, a solid tumor of early childhood. Our results indicated significantly higher single nucleotide variants in relapse tumors, gave hints for branched tumor evolution upon treatment and clonal selection as deduced from shifts in allelic frequencies between primary and relapsing neuroblastoma. Here, we will review these findings and give an outlook on dealing with intratumoral heterogeneity and sub-clonal diversity in neuroblastoma for future targeted treatments.

Prevention and treatment of relapse after stem cell transplantation in lymphoid malignancies.

PubMed

Sureda, Anna; Dreger, Peter; Bishop, Michael R; Kroger, Nicolaus; Porter, David L

2018-05-24

Relapse is now the major cause of treatment failure after allogeneic HSCT (alloHSCT). Many novel strategies to address this critical issue are now being developed and tested. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg, Germany in November 2016, international experts presented and discussed recent developments in the field. Some approaches may be applicable to a wide range of patients after transplant, whereas some may be very disease-specific. We present a report from the session dedicated to issues related to prevention and treatment of relapse of lymphoid malignancies after alloHSCT. This session included detailed reviews as well as forward-looking commentaries that focused on Hodgkin lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma, diffuse large cell and follicular lymphoma, and multiple myeloma.

Smoking habit and gastritis histology.

PubMed

Namiot, A; Kemona, A; Namiot, Z

2007-01-01

Long-term cigarette smoking may increase the risk of digestive tract pathologies, however, what is the influence smoking habit on gastric mucosa histology is still poorly elicited. The aim of the study was to compare histological evaluation of gastritis in smoker and non-smoker groups. A total of 236 patients of various H. pylori status (109 infected, 127 non-infected), clinical diagnosis (107 duodenal ulcer disease, 129 dyspepsia), and smoking habit (92 smokers, 144 non-smokers) were included. Subjects were classified as smokers if they smoked 5 or more cigarettes per day for at least 3 years. A histological examination of endoscopically obtained samples was performed by two experienced pathomorphologists blinded to the diagnoses and smoking habit. Microscopic slices of the gastric mucosa were stained with hematoxylin-eosin and Giemsa. Apart from histological diagnosis, H. pylori status was additionally confirmed by an urease test (CLO-test) at least in one of two gastric locations (antrum or corpus). In the H. pylori infected population, H. pylori density, neutrophils, and mononuclear cells infiltration in the gastric corpus mucosa were lower in smokers than non-smokers, while in the antrum the differences were not significant. In the non-infected population, no significant differences in neutrophils and mononuclear cells infiltration between smokers and non-smokers were found. Since the significant differences in studied parameters of chronic gastritis between smokers and non-smokers were found in the corpus mucosa of H. pylori infected subjects, smoking should be taken into account when a histological evaluation of the gastric mucosa in the H. pylori infected population is performed.

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

PubMed

Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

2018-05-02

The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Extramedullary Relapse of Acute Lymphoblastic Leukemia Presenting as Abnormal Uterine Bleeding: A Case Report.

PubMed

Robillard, Diana T; Kutny, Matthew A; Chewning, Joseph H; Arbuckle, Janeen L

2017-06-01

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Relapse of ALL occurs in 15%-20% of patients, with 2%-6% occurring exclusively in extramedullary sites. Relapse of ALL in gynecologic organs is extremely rare. We present a case of a 12-year-old girl with a history of ALL who was referred to the pediatric gynecology clinic with abnormal uterine bleeding. She was determined to have an extramedullary uterine relapse of her ALL. Abnormal uterine bleeding in the setting of childhood malignancy is a frequent reason for consultation to pediatric and adolescent gynecology services. This bleeding is commonly attributed to thrombocytopenia due to bone marrow suppressive chemotherapeutic agents. However, as shown in this report, abnormal uterine bleeding might be a manifestation of an extramedullary relapse. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind Placebo-Controlled Trial

PubMed Central

Phillips, Katharine A.; Keshaviah, Aparna; Dougherty, Darin; Stout, Robert L.; Menard, William; Wilhelm, Sabine

2016-01-01

Objective Body dysmorphic disorder (BDD) is common, distressing, and often severely impairing. Serotonin-reuptake inhibitors (SRIs) appear efficacious for BDD, but the few existing pharmacotherapy studies were short-term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted. We report results from the first BDD relapse prevention study. Method Adults (N=100) with DSM-IV BDD received open-label escitalopram for 14 weeks (Phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for six months (Phase 2). Reliable and valid outcome measures were utilized. Results Phase 1: Overall, 67.0% of treated subjects and 81.1% of completers were escitalopram responders (p’s<0.0001). BDD severity, BDD-related insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of Phase 1 (all p's<0.0001). Phase 2: Time to relapse was significantly longer for subjects receiving escitalopram than those receiving placebo (hazard ratio=2.72, 95% CI [1.01, 8.57], p=0.049). Phase 2 relapse proportions were 18% for escitalopram versus 40% for placebo. In escitalopram-treated subjects, BDD severity significantly decreased over time during the continuation treatment phase (p=0.036); further improvement occurred in 35.7% of the escitalopram group. There were no significant group differences in BDD severity, insight, depressive symptoms, psychosocial functioning, or quality of life. Conclusions Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed compared with placebo-treated subjects. BDD severity significantly further improved during six additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects had further improvement during continuation phase treatment. PMID:27056606

Pharmacotherapy Relapse Prevention in Body Dysmorphic Disorder: A Double-Blind, Placebo-Controlled Trial.

PubMed

Phillips, Katharine A; Keshaviah, Aparna; Dougherty, Darin D; Stout, Robert L; Menard, William; Wilhelm, Sabine

2016-09-01

Body dysmorphic disorder is common, distressing, and often severely impairing. Serotonin reuptake inhibitors appear efficacious, but the few existing pharmacotherapy studies were short term (≤4 months), and no relapse prevention studies or continuation phase studies have been conducted to the authors' knowledge. The authors report results from the first relapse prevention study in body dysmorphic disorder. Adults (N=100) with DSM-IV body dysmorphic disorder received open-label escitalopram for 14 weeks (phase 1); 58 responders were then randomized to double-blind continuation treatment with escitalopram versus switch to placebo for 6 months (phase 2). Reliable and valid outcome measures were utilized. In phase 1, 67.0% of treated subjects and 81.1% of subjects who completed phase 1 responded to escitalopram. Body dysmorphic disorder severity (in both the intent-to-treat and the completer groups) and insight, depressive symptoms, psychosocial functioning, and quality of life significantly improved from baseline to end of phase 1. In phase 2, time to relapse was significantly longer with escitalopram than with placebo treatment (hazard ratio=2.72, 95% CI=1.01-8.57). Phase 2 relapse proportions were 18% for escitalopram and 40% for placebo. Among escitalopram-treated subjects, body dysmorphic disorder severity significantly decreased over time during the continuation phase, with 35.7% of subjects showing further improvement. There were no significant group differences in body dysmorphic disorder severity or insight, depressive symptoms, psychosocial functioning, or quality of life. Continuation-phase escitalopram delayed time to relapse, and fewer escitalopram-treated subjects relapsed than did placebo-treated subjects. Body dysmorphic disorder severity significantly improved during 6 additional months of escitalopram treatment following acute response; more than one-third of escitalopram-treated subjects experienced further improvement.

Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

PubMed

Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

2011-06-01

Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

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

Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma.

PubMed

Zahid, Umar; Shaukat, Al-Aman; Hassan, Nida; Anwer, Faiz

2017-10-01

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

PubMed

O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

2015-04-01

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly

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

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.

Clinical outcome of patients with early stage favorable Hodgkin lymphoma treated with ABVD × two cycles followed by FDG-PET/CT restaging and 20 Gy of involved-site radiotherapy.

PubMed

Kamran, Sophia C; Jacene, Heather A; Chen, Yu-Hui; Mauch, Peter M; Ng, Andrea K

2018-06-01

Our purpose was to assess outcome of patients with early-stage, favorable (per GHSG criteria) Hodgkin Lymphoma (HL) staged with FDG-PET/CT and treated with two cycles of adriamycin, bleomycin, vincristine, and dacarbazine (ABVD) followed by PET/CT assessment and involved-site radiotherapy (ISRT) to 20 Gy. Records of 23 patients who met eligibility criteria, treated between 2008 and 2016, were reviewed. PET response after two cycles of ABVD was independently assessed by a nuclear medicine physician. After two cycles of ABVD, 91.3% of patients had a Deauville score of 1-2; 1 patient had a score of 3. Median follow-up was 45.3 months. As of this analysis, all patients are alive without disease. One patient had an out-of-field relapse, yielding a 4-year relapse-free survival rate of 92.9% (95%CI [59.1, 99.0]). Our results showed that with careful patient selection by initial disease characteristics and FDG-PET response to chemotherapy, the use of a more restricted treatment volume of ISRT to 20 Gy following ABVD × 2 is associated with excellent outcomes.

A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse

PubMed Central

Xue, Yan-Xue; Luo, Yi-Xiao; Wu, Ping; Shi, Hai-Shui; Xue, Li-Fen; Chen, Chen; Zhu, Wei-Li; Ding, Zeng-Bo; Bao, Yan-ping; Shi, Jie; Epstein, David H.; Shaham, Yavin; Lu, Lin

2013-01-01

Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence. PMID:22499948

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.

HIGH-DOSE CHEMOTHERAPY WITH BLOOD OR BONE MARROW TRANSPLANTS FOR RHABDOMYOSARCOMA

PubMed Central

Stiff, Patrick J.; Agovi, Manza-A.; Antman, Karen H.; Blaise, Didier; Camitta, Bruce M.; Cairo, Mitchell S.; Childs, Richard W.; Edwards, John R; Gale, Robert Peter; Hale, Gregory A.; Lazarus, Hillard M.; Arora, Mukta

2009-01-01

Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, 5 year survival for those who relapse is about 30% and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone marrow transplants for RMS between 1989 and 2003 and reported to CIBMTR. Histological subtype was confirmed by reviewing pathology reports. Transplant-related mortality (TRM), progression-free survival (PFS) and survival were evaluated. Overall 73% of subjects were < 20 years; 39% had cancer bulk >5cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant and 67% were in 1st remission. The 1-year TRM was 5% (95% CI, 1–12%) and the 5 year PFS and survival were 29% (95% CI, 18–41%) and 32% (95% CI, 21–44%) respectively. There was only a 4% relapse rate after the first year. There were no differences in 5 year PFS or survival based on histological subtype, transplant in 1st remission vs. relapse (36% vs. 29%; p=0.5), or transplantation for poor-risk histologies in 1st remission vs. relapse (34% vs. 33%; p=0.9). Our data indicate that autotransplants for RMS disease are typically done in patients with disease responsive to chemotherapy pretransplant, with approximately one-third long-term survivors. Despite high risk factors, we also found a low TRM, perhaps reflecting the migration from marrow to blood stem cells as the graft source. Even when performed after relapse for alveolar/undifferentiated histologies, long-term survivals were seen seemingly better than results with conventional therapies. PMID:19961947

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.

Comparative efficacy of first-line natalizumab vs IFN-β or glatiramer acetate in relapsing MS

PubMed Central

Kalincik, Tomas; Jokubaitis, Vilija; Zhang, Annie; Pellegrini, Fabio; Wiendl, Heinz; Belachew, Shibeshih; Hyde, Robert; Verheul, Freek; Lugaresi, Alessandra; Havrdová, Eva; Horáková, Dana; Grammond, Pierre; Duquette, Pierre; Prat, Alexandre; Iuliano, Gerardo; Terzi, Murat; Izquierdo, Guillermo; Hupperts, Raymond M.M.; Boz, Cavit; Pucci, Eugenio; Giuliani, Giorgio; Sola, Patrizia; Spitaleri, Daniele L.A.; Lechner-Scott, Jeannette; Bergamaschi, Roberto; Grand'Maison, François; Granella, Franco; Kappos, Ludwig; Trojano, Maria; Butzkueven, Helmut

2016-01-01

Abstract Background: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score–matched cohorts from observational multiple sclerosis registries. Methods: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n = 366/group) and subgroups with higher baseline disease activity. Results: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) (p [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28–0.47; p < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58–0.93; p = 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale–time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups. Conclusions: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients. Classification of evidence: This study

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.

Depression, Craving, and Substance Use Following a Randomized Trial of Mindfulness-Based Relapse Prevention

ERIC Educational Resources Information Center

Witkiewitz, Katie; Bowen, Sarah

2010-01-01

Objective: A strong relation between negative affect and craving has been demonstrated in laboratory and clinical studies, with depressive symptomatology showing particularly strong links to craving and substance abuse relapse. Mindfulness-based relapse prevention (MBRP), shown to be efficacious for reduction of substance use, uses…

How I manage relapse of chronic myeloid leukaemia after stopping tyrosine kinase inhibitor therapy.

PubMed

Rea, Delphine; Mahon, François-Xavier

2018-01-01

During the last 10 years, clinical trials formally demonstrated that about 50% of patients with chronic phase (CP) chronic myeloid leukaemia (CML) who achieve and maintain deep molecular responses for a prolonged period of time during treatment with imatinib or new generation tyrosine kinase inhibitors (TKIs) may successfully stop their anti-leukaemic therapy. Based on the accumulated knowledge from abundant clinical trial experience, TKI discontinuation is becoming an important goal to achieve and is about to enter clinical practice. This review focuses on relapse definition, laboratory tests to identify relapse and relapse management after TKI discontinuation. © 2017 John Wiley & Sons Ltd.

Using web-based animations to teach histology.

PubMed

Brisbourne, Marc A S; Chin, Susan S-L; Melnyk, Erica; Begg, David A

2002-02-15

We have been experimenting with the use of animations to teach histology as part of an interactive multimedia program we are developing to replace the traditional lecture/laboratory-based histology course in our medical and dental curricula. This program, called HistoQuest, uses animations to illustrate basic histologic principles, explain dynamic processes, integrate histologic structure with physiological function, and assist students in forming mental models with which to organize and integrate new information into their learning. With this article, we first briefly discuss the theory of mental modeling, principles of visual presentation, and how mental modeling and visual presentation can be integrated to create effective animations. We then discuss the major Web-based animation technologies that are currently available and their suitability for different visual styles and navigational structures. Finally, we describe the process we use to produce animations for our program. The approach described in this study can be used by other developers to create animations for delivery over the Internet for the teaching of histology.

Neurocognitive rehabilitation for addiction medicine: From neurophysiological markers to cognitive rehabilitation and relapse prevention.

PubMed

Campanella, Salvatore

2016-01-01

Currently, relapse prevention remains the main challenge in addiction medicine, indicating that the established treatment methods combining psychotherapy with neuropharmacological interventions are not entirely effective. Therefore, there is a push to develop alternatives to psychotherapy- and medication-based approaches to addiction treatment. Two major cognitive factors have been identified that trigger relapse in addicted patients: attentional biases directed toward drug-related cues, which increase the urge to consume, and impaired response inhibition toward these cues, which makes it more difficult for addicted people to resist temptation. Recent studies on newly detoxified alcoholic patients have shown that by using the appropriate tasks to index these cognitive functions with event-related potentials (ERPs), it is possible to discriminate between future relapsers and nonrelapsers. These preliminary data suggest that the ERP technique has great clinical potential for preventing relapse in alcohol-dependent patients, as well as for addictive states in general. Indeed, ERPs may help to identify patients highly vulnerable to relapse and allow the development of individually adapted cognitive rehabilitation programs. The implementation of this combined approach requires an intense collaboration between psychiatry departments, clinical neurophysiology laboratories, and neuropsychological rehabilitation centers. The potential pitfalls and limitations of this approach are also discussed. © 2016 Elsevier B.V. All rights reserved.

Prevention of relapse in patients with congestive heart failure: the role of precipitating factors

PubMed Central

Feenstra, J; Grobbee, D; Jonkman, F; Hoes, A; Stricker, B

1998-01-01

Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF.

 Keywords: congestive heart failure;  precipitating factors;  prevention PMID:9930039

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

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.

Allogeneic stem cell transplantation using lymphoablative rather than myeloablative conditioning regimen for relapsed or refractory lymphomas.

PubMed

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

2017-03-01

In relapsed or refractory non-Hodgkin lymphoma (NHL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides graft-versus-lymphoma activity resulting in fewer incidences of relapse. However, therapy-related mortality (TRM) remains an important challenge. We attempted to introduce our reduced-intensity conditioning (RIC) regimen. From 2007 to 2013, we treated 28 relapsed or refractory NHLs with allo-HSCT. All were pre-conditioned with fludarabine [FLU, 180 mg/body surface area (BSA)/6 days] and melphalan (MEL, 70 mg/BSA/1 day); 25 (all but 3) were additionally treated with total body irradiation (TBI, 800 cGy/4Fx/2 days). Peripheral blood stem cells were collected from matched siblings (n = 10) or suitably matched unrelated (n = 18) donors. There were eight diffuse large B-cell lymphomas, seven peripheral T-cell lymphoma not otherwise specified, give lymphoblastic lymphomas, two mantle cell lymphomas, and six various other lymphomas. Of these patients, 10 relapsed after auto-HSCT, 5 relapsed after chemotherapy, and 13 were refractory lymphomas. After allo-HSCT, complete remission was achieved in 22 (78.5%) patients. After a median follow-up of 24.8 months, 3-year overall survival and disease-free survival were 62.4 and 59.2% and the 3-year TRM and relapse incidence were 14.9 and 28.6% respectively. Acute and chronic graft-versus-host diseases (GVHDs) were identified in 17 (≥Grade II in 12 patients) and 18 patients respectively, and the group with chronic GVHD showed favourable survival outcomes. In relapsed or refractory NHL, RIC-allo-HSCT using FLU + MEL + 800 cGy TBI showed favourable survival outcomes with acceptable TRM and relapse incidence. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Relapse surveillance in AFP-positive hepatoblastoma: re-evaluating the role of imaging.

PubMed

Rojas, Yesenia; Guillerman, R Paul; Zhang, Wei; Vasudevan, Sanjeev A; Nuchtern, Jed G; Thompson, Patrick A

2014-10-01

Children with hepatoblastoma routinely undergo repetitive surveillance imaging, with CT scans for several years after therapy, increasing the risk of radiation-induced cancer. The purpose of this study was to determine the utility of surveillance CT scans compared to serum alpha-fetoprotein (AFP) levels for the detection of hepatoblastoma relapse. This was a retrospective study of all children diagnosed with AFP-positive hepatoblastoma from 2001 to 2011 at a single institution. Twenty-six children with hepatoblastoma were identified, with a mean age at diagnosis of 2 years 4 months (range 3 months to 11 years). Mean AFP level at diagnosis was 132,732 ng/ml (range 172.8-572,613 ng/ml). Five of the 26 children had hepatoblastoma relapse. A total of 105 imaging exams were performed following completion of therapy; 88 (84%) CT, 8 (8%) MRI, 5 (5%) US and 4 (4%) FDG PET/CT exams. A total of 288 alpha-fetoprotein levels were drawn, with a mean of 11 per child. The AFP level was elevated in all recurrences and no relapses were detected by imaging before AFP elevation. Two false-positive AFP levels and 15 false-positive imaging exams were detected. AFP elevation was found to be significantly more specific than PET/CT and CT imaging at detecting relapse. We recommend using serial serum AFP levels as the preferred method of surveillance in children with AFP-positive hepatoblastoma, reserving imaging for the early postoperative period, for children at high risk of relapse, and for determination of the anatomical site of clinically suspected recurrence. Given the small size of this preliminary study, validation in a larger patient population is warranted.

Metabolic shift of the kynurenine pathway impairs alcohol and cocaine seeking and relapse.

PubMed

Vengeliene, Valentina; Cannella, Nazzareno; Takahashi, Tatiane; Spanagel, Rainer

2016-09-01

The glutamatergic system plays a key role in the maintenance of drug use and development of drug-related conditioned behaviours. In particular, hyper-glutamatergic activity and N-methyl-D-aspartate receptor (NMDAR) activation may drive drug craving and relapse. Inhibition of kynurenine-3-monooxygenase (KMO) shifts the metabolic kynurenine pathway towards production of kynurenic acid, which leads to a reduction of glutamatergic/NMDAR activity via different mechanisms. In this study, we investigated whether drug-seeking and relapse behaviour could be modified by the metabolic shift of endogenous kynurenine pathway. An inhibitor of kynurenine-3-monooxygenase (KMO) Ro61-8048 (4 and 40 mg/kg) and its prodrug JM6 (100 and 200 mg/kg) were tested in two behavioural rat models for drug seeking and relapse-the alcohol deprivation effect (ADE) model in long-term alcohol-drinking rats and the model of cue-induced reinstatement of alcohol- and cocaine-seeking behaviour. Our results show that relapse-like alcohol drinking during the ADE was abolished by repeated intraperitoneal administration of Ro61-8048 and significantly reduced by its oral prodrug JM6. Cue-induced reinstatement of both alcohol- and cocaine-seeking behaviour was also abolished by administration of Ro61-8048. Pharmacological enhancement of endogenous kynurenic acid levels provides a novel treatment strategy to interfere with glutamatergic/NMDAR activity as well as with craving and relapse in alcohol-dependent patients and drug addicts.

Factors associated with the risk of relapse in schizophrenic patients after a response to electroconvulsive therapy: a retrospective study.

PubMed

Shibasaki, Chiyo; Takebayashi, Minoru; Fujita, Yasutaka; Yamawaki, Shigeto

2015-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression and schizophrenia. However, there is a high rate of relapse after an initial response to ECT, even with antidepressant or antipsychotic maintenance therapy. This study was carried out to examine the factors that influence the risk of relapse in schizophrenic patients after a response to ECT. We retrospectively reviewed the records of 43 patients with schizophrenia who received and responded to an acute ECT course. We analyzed the associated clinical variables and relapse after response to the acute ECT. Relapse was defined as a Clinical Global Impressions Improvement score ≥6 or a psychiatric rehospitalization. All patients were treated with neuroleptic medication after the acute ECT course. The relapse-free rate of all 43 patients at 1 year was 57.3%, and the median relapse-free period was 21.5 months. Multivariate analysis showed that the number of ECT sessions was associated with a significant increase in the risk of relapse (hazard ratio: 1.159; P=0.033). Patients who were treated with adjunctive mood stabilizers as maintenance pharmacotherapy after the response to the acute ECT course were at a lower risk of relapse than were those treated without mood stabilizers (hazard ratio: 0.257; P=0.047). Our study on the recurrence of schizophrenia after a response to an acute ECT course suggests that the number of ECT sessions might be related to the risk of relapse and that adjunctive mood stabilizers might be effective in preventing relapse.