Relapse Prevention Strategies Research Articles

The role and novel use of natural killer cells in graft-versus-leukemia reactions after allogeneic transplantation

Allogeneic hematopoietic cell transplantation (HCT) has transformed over the past several decades through enhanced supportive care, reduced intensity conditioning (RIC), improved human leukocyte antigen (HLA) typing, and novel graft-versus-host disease (GVHD)-prevention and treatment strategies. Most notably, the implementation of post-transplantation cyclophosphamide (PTCy) has dramatically increased the safety and availability of this life-saving therapy. Given reductions in nonrelapse mortality (NRM) with these advances, the HCT community has placed even greater emphasis on developing ways to reduce relapse - the leading cause of death after HCT. When using RIC HCT, protection from relapse relies predominantly on graft-versus-leukemia (GVL) reactions. Donor lymphocyte infusion (DLI), adoptive cellular therapy, checkpoint inhibition, and post-HCT maintenance strategies represent approaches under study that aim to augment or synergize with the GVL effects of HCT. Optimizing donor selection algorithms to leverage GVL represents another active area of research. Many of these strategies seek to harness the effects of T cells, which for decades were felt to be the primary mediators of GVL and the focus of investigation in relapse reduction. However, there is growing interest in capitalizing on the ability of natural killer (NK) cells to yield potent anti-tumor effects. A potential advantage of NK cell-based approaches over T cell-mediated is the potential to reduce NRM in addition to relapse. By decreasing infection, without increasing the risk of GVHD, NK cells may mitigate NRM, while still yielding relapse reduction through identification and clearance of cancer cells. Most T cell-focused relapse-prevention strategies must weigh the benefits of relapse reduction against the increased risk of NRM from GVHD. In contrast, NK cells have the potential to reduce both, potentially tipping the scales significantly in favor of survival. Here, we will review the role of NK cells in GVL, optimization of NK cell match or mismatch, and burgeoning areas of research in NK cell therapy such as adoptive transfer and chimeric antigen receptor (CAR) NK cells.

INTEGRATING PSYCHOEDUCATION INTO MOTIVATIONAL THERAPY: A PROTOCOL FOR POSITIVE CHANGE IN DEPRESSIVE SUBJECTS

The combination of psychoeducation and motivational therapy is proved to be a powerful approach to help individuals making positive changes in their lives.(Miller & Rollnick, 2013) This scientific paper provides practitioners with information on a draft protocol for psychoeducation in motivational therapy,which is combining the two approaches to optimize the change process. This protocol emphasizes the importance of tailoring treatment to the patient's individual needs, and reinforcing the motivation induced to promote lasting change. The protocol begins with the establishment of a trusting relationship between therapist and patient, followed by in-depth information on the problem to be treated. Next, sessions are organized to explore motivation, identify the advantages and disadvantages of change, set goals for change and, finally, reinforce the skills needed to achieve these goals. In addition, relapse prevention strategies are discussed with the patient, and a long-term support plan is drawn up involving his collaboration. This protocol offers a holistic and personalized approach to guide practitioners in the application of psychoeducation in motivational therapy, promoting positive and lasting results for people seeking change. The scientific paper concludes by highlighting the interest of this integrated approach for a variety of issues in Depressive Subjects, while emphasizing the need for follow-up sessions to maintain progress and ongoing support

A Significant Area of Research on Relapse Prevention in Addiction Treatment: Drug-Related Dreams

Drug-related dreams (DD) are dreams experienced by addicted individuals during withdrawal or recovery processes, containing various content related to substance use. Nowadays, it has been suggested that drug-related dreams have a two-way prognostic value, positively and negatively influencing individuals' desires for substance use. While DDs are routinely implemented as a relapse prevention strategy in some addiction clinics abroad, the clinical significance of such dreams has not been sufficiently recognized in our country yet. This editorial aims to provide definitions of these types of dreams and offer practical recommendations for implementation in addiction clinics in our country, which could be significant.

The Outcome of Diffuse Large B-Cell Lymphoma Patients with Testicular Involvement - Real World Data

Introduction: Patients (pts) with testicular lymphoma (TL) have an increased risk of central nervous system (CNS) relapse. In rituximab era, the reported incidence vary from 10% (in limited disease) to 25% (advanced disease). More data is needed to guide the managment of TL pts in current era. Optimal strategy for CNS relapse prevention is uncertain. Methods: We studied consecutive pts diagnosed between 2000 and 2022 with testicular diffuse large B-cell lymphoma (DLBCL) prospectively observed in the Czech Lymphoma Study Group Project NiHiL (Clinical Trial gov. NCT03199066). Objectives were to analyze the cumulative incidence of CNS relapse, time to CNS relapse, PFS and OS. The impact of various treatment strategies on CNS relapse was analyzed. Results: We identified 229 pts with testicular involvement: 157 pts with primary testicular lymphoma (PTL) in clinical stage I or II and 72 pts in advanced stage (AD) III or IV. Median age was 70 years (range 33 - 87). Rituximab-based chemotherapy received 192 (83.8%) pts including 127 (81%) cases with PTL. Following localized treatments were used more often in PTL compared to AD: unilateral orchiectomy [148 (94.3%) vs. 47 (65.3%); p < 0.0001], testicular irradiation (RT) [116 (61.7%) vs. 40 (38.7%); p = 0.005]. Most patients (85%) received some form of CNS prophylaxis. There were similar rates in use of prophylactic methotrexate (MTX) between PTL and AD (p = 0.88): intrathecal (i.t.) MTX 64 (40.8%) vs. 29 (40.3%), intravenous (i.v.) MTX with or without cytarabine 20 (12.8%) vs. 7 (9.7%); combined i.t. and i.v. MTX 38 (24.2%) vs. 20 (27.8%). Out of 229 cases 25 (15.9%) PTL and 11 (15.3%) AD pts did not receive any CNS prophylaxis. Median follow-up was 51.8 months.Overall 63 (27.5%) pts relapsed including 14 (6.1%) relapses in CNS. Median time to CNS relapse was 21.9 months and to other systemic relapse was 14.7 months (p = 0.63). The 5-year cumulative incidence of CNS relapse in PTL was 4.55% (95% confidence interval [CI], 0.1 - 28.6) and in AD 12.07% (95% CI 0.8 - 39.6), respectively. In univariate analyses, MTX prophylaxis (i.v. and/or i.t.) and testicular RT had no impact on CNS relapse (p = 0.49 and p = 0.60, respectively). Orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (hazard ratio [HR] = 0.11[95% CI 0 - 0.124]; p = 0.001). Rituximab significantly reduced CNS relapse in AD with testicular involvement (HR = 0.1002 [95% CI 0.0 - 0.45]; p = 0.0005). Out of 14 pts with CNS relapse 8 died due to lymphoma progression. Median progression-free survival (PFS) and overall survival (OS) in PTL was significantly better when compared to AD (PFS 92.9 vs. 28.1 months, p < 0.0006; OS 108.7 vs. 56.7 months, p = 0.0002). Median PFS2 and OS2 since CNS relapse was dismal in AD compared to PTL (PFS2 1.6 vs. 37.8 months, p = 0.04 and OS2 2.3 vs. 37.8 months, p = 0.05). Conclusions: The rate of CNS relapses in PTL and advanced disease with testicular involvement is lower than previously reported. This study confirmed a significant favorable impact of rituximab in prevention of CNS relapse. Notably, methotrexate prophylaxis i.v. or i.t. did not alter the CNS relapse risk. Prognosis of CNS relapse is particularly poor in advanced disease. This work was supported by grant AZV NU21-03-00411 from the Ministry of Health of the Czech Republic and by the Cooperatio Program, research area “Oncology and Haematology”

Preferential Efficacy of Remission Maintenance with HDC/IL-2 in Age Groups of Patients with Chemoresponsive or Normal Karyotype AML

Background Relapse in complete remission (CR) remains a leading cause of morbidity and mortality in acute myeloid leukemia (AML). Previous phase 3 trial data show that combinatorial immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) reduces relapse incidence in the post-consolidation phase, in particular among younger adult AML patients (<60 years old) in CR1 (Brune et al., Blood 108:88). Recent post-hoc analyses identified subgroups of responding patients including (1) those achieving CR1 after the first induction course of chemotherapy (referred to as chemoresponsive AML) and (2) those carrying leukemic cells of normal karyotype (NK-AML), i.e. devoid of structural or numerical chromosomal aberrations. Here we report analyses of treatment efficacy in a phase 3 trial within age groups of patients with chemoresponsive AML or NK-AML. Methods Three hundred and twenty AML patients (18-84 years old, median 57) who were ineligible for allogeneic stem cell transplantation were randomly assigned to receive HDC/IL-2 or no treatment (control) for remission maintenance in a phase 3 trial. Patients were recruited in Europe, Israel, Oceania, and USA. Treatment was initiated in CR after the completion of consolidation chemotherapy and comprised 10 consecutive 3-week cycles of HDC/IL-2 for 18 months (mo) with 3- or 6-week rest periods. In each cycle, patients received HDC at 0.5 mg and human recombinant low-dose IL-2 (aldesleukin; 16,400 IU/kg) s.c. twice daily (n=160) or no treatment (control; n=160). After 18 months of treatment, all patients were monitored for >18 additional mo (median follow-up 48 mo). Results Among study subjects in CR1 203/261 (78%) of evaluable patients attained CR after the first induction cycle (chemoresponsive AML) and 128/220 (58%) had NK-AML. Within both subgroups, analysis of efficacy by age at diagnosis implied preferred benefit of HDC/IL-2 vs. control in patients 40-59 years old (Figure 1) with independent efficacy in patients 40-49 and 50-59 years old (Table 1). The treatment arm was not significantly superior over the control arm for LFS or OS in the youngest patients (18-39 years old) or in patients >60 years old (P>0.2, logrank test, for all comparisons (LFS and OS)) within subgroups of chemosensitive AML or NK-AML. Conclusions We speculate that the observed benefit of HDC/IL-2 in patients responding swiftly to initial chemotherapy may be explained by more efficient immune-mediated elimination of leukemic cells at a lower burden of leukemia. The preferential efficacy of HDC/IL-2 in NK-AML points towards efficacy in subgroups of leukemic mutations that are less common in the youngest group of patients. The reason for the lack of significant efficacy in patients >60 years old, despite achievement of CR1 after the initial chemotherapy and despite having NK-AML, remains unknown but may be explained by fading anti-leukemic immunity in old patients. Overall, these findings may be considered for the selection of patients suitable for immunotherapy with HDC/IL-2 in an emerging landscape of strategies for relapse prevention in AML.

Prophylactic or Preemptive Donor-Derived CD19 CAR-T Cell Infusion for Preventing Relapse in High-Risk B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Relapse remains a significant challenge in the management of high-risk B-cell acute lymphoblastic leukemia (B-ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Existing post-transplant relapse prevention strategies for high-risk B-ALL patients after transplantation, particularly in cases of Philadelphia chromosome-negative B-ALL, have limitations and suboptimal efficacy. This study aims to evaluate the efficacy and safety profile of prophylactic or preemptive infusion of donor-derived CD19 chimeric antigen receptor T (CAR-T) cells in high-risk B-ALL patients after allo-HSCT. Methods: Between May 2017 and July 2022, high-risk B-ALL patients with minimal residual disease (MRD) positive or MRD negative status after allo-HSCT were enrolled in clinical trials of donor-derived CD19 CAR-T cell therapy (ChiCTR 2000041025 and ChiCTR-ONN-16009862). The primary outcome was the cumulative incidence of relapse (CIR). Secondary outcomes were progression-free survival (PFS), overall survival (OS) and CAR-T cell treatment-related toxicities. Results: A total of 25 high-risk B-ALL patients who received infusion of donor-derived CD19 CAR-T cells after allo-HSCT were enrolled in the CAR-T cell group, including 8 patients with MRD and 17 patients without MRD. A contemporaneous cohort of 43 high-risk B-ALL patients who did not receive CAR-T cell therapy in MRD-positive or MRD-negative status after transplantation was also included as a control group. The median age of patients enrolled in the CAR-T group was 29 years (range: 9-60 years). The median infused CAR-T cell dose was 2.5×10^6/kg (range: 1.0-5.0×10^6/kg), with a median time from transplantation to CAR-T cell treatment of 122 days (range: 45-315 days). The median follow-up duration was 23.6 months (range: 8.3-60.6 months). Of the 25 patients in CAR-T group, eight MRD-positive patients achieved MRD-negative remission after CAR-T cells treatment (Figure1A). The two-year cumulative incidence of relapse in the CAR-T cell group was significantly lower at 4.8% (95% CI: 0.0%-12.6%) compared to the control group's incidence of 26.6% (95% CI: 11.4%-41.8%, P = 0.03，Figure1B). Additionally, the CAR-T cell group exhibited a higher two-year PFS rate [86.3% (95% CI: 71.8%-100%)] compared to the control group [63.5% (95% CI: 48.0%-79.0%), P = 0.04]. However, the two-year OS rates were comparable between the CAR-T cell group [91.0% (95% CI: 79.0%-100%)] and the control group [79.1% (95% CI: 66.0%-92.2%), P = 0.20]. Adverse events were well tolerated, and no patients experienced grade 3-4 cytokine release syndrome or any grade of immune effector cell-associated neurotoxicity syndrome. Hematological cytopenia was the most severe CAR-T cell related toxicity, but the toxicity was manageable, and only three patients experienced acute graft-versus-host disease following CAR-T cell infusion. Conclusions: Prophylactic or preemptive infusion of CAR-T cells after allo-HSCT demonstrated a reduced incidence of relapse and acceptable adverse events in high-risk B-ALL patients. These findings highlight the potential of CAR-T cell therapy as a promising strategy for relapse prevention in high-risk B-ALL patients after allo-HSCT.

Are sleep and circadian rhythm disturbances the cause or simply the consequence of depression or other mood disorder sub-types?

An area of great interest in Depression and Mood Disorder research has been highlighted by the Mental Health Priority Area of the Wellcome Trust (UK), namely sleep and circadian rhythm disturbances (SCRD). Wellcome has set out the background logic for this focus and clear research priorities (Wellcome Trust, 2022), leading to the funding of a series of international projects. This focus is a particularly good fit with the international agenda for development of more effective and scalable strategies for prevention, early intervention and secondary prevention of illness relapse, progression and downstream physical illnesses for adolescent-onset anxiety, depressive and psychotic disorders (Hickie et al., 2019).

Amiodarone prevention for atrial fibrillation relapse after surgical ablation

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder. AF ablation based on endovascular or surgical techniques is a standard of care in everyday practice. Early recurrence of atrial arrhythmias is a significant problem after ablative procedures. Prophylactic use of antiarrhythmic drugs has become a possible solution. Materials and methods: We performed a retrospective observational cohort study of 59 patients with heart disease requiring surgery under extracorporeal circulation (ECC) and have received radiofrequency ablation (RFA) for chronic or persistent AF with a successful conversion to sinus rhythm. Patients were divided into two groups: 36 were treated with amiodarone for three months postoperatively (treatment group), and 23 had no concomitant amiodarone therapy (control group). We compared the groups regarding freedom from recurrent atrial arrhythmia and the frequency of conduction disorders requiring permanent pacemaker implantation. Results: No differences between the groups were found regarding demographic characteristics, risk profile, and heart diseases indicating cardiac surgery. During follow-up, a significantly higher proportion of patients with sinus rhythm in the group receiving amiodarone was found (80.56% vs. 52.17%; p < 0.041). No cases of premature discontinuation of amiodarone for side effects or noncompliance were registered in the treatment group. Conclusion: Three months of amiodarone therapy post-surgical RFA of AF is an effective and safe strategy for relapse prevention.

Adoptive Immunotherapy via Donor Lymphocyte Infusions following Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis: A Real-World, Retrospective Multicenter Study

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option for Myelofibrosis (MF). Relapse however remains a significant problem in up to 20-30% of cases. Donor Lymphocyte Infusions (DLI) represent a potentially effective strategy for relapse prevention and management, but optimal timing based on measurable residual disease (MRD)/chimerism analyses and regimen choice remain undetermined. We performed a retrospective 'real world' analysis of a multicentre cohort of MF allo-HCT patients from 8 European transplant centres who received DLI between 2005-2022. Response was assessed using IWG-MRT defined response criteria, and survival endpoints were estimated using the Kaplan-Meier estimator and log-rank test. The study included 28 patients with a median age of 58 years and a Karnofsky performance status of >80. The majority of patients had DIPPS-plus Intermediate-2 or high-risk disease at the time of allo-HCT. In vivo T cell depletion was utilised in 20 (71.2%) cases, with 19/20 patients receiving anti-thymocyte globulin (ATG). Indication for DLI was either 'pre-emptive' (n=15), due to a decrease in recipient chimerism (n=13) or molecular relapse (n=2), or 'therapeutic' (n=13) for clinician-defined haematological/ clinical relapse. No patient received DLI prophylactically. Median time to DLI administration was 23.4 months post allo-HCT. Of the 16 patients receiving >1 dose of DLI, 12 were part of a planned escalating dose regimen. Median follow-up from time of 1st DLI administration was 55.4 months. Response rates to DLI were CR (n=9), PR (n=1), and clinical improvement (n=6). Chimerism levels improved in 16 patients, and stable disease was reported in 5 patients. No response or progression was reported in 7 patients. DLI-induced aGVHD was reported in 11 (39%) cases, grade 3/4 (n=7;25%). Median overall survival from time of 1st DLI was 62.6 months, and the cumulative incidence of relapse/progression after 1st DLI was 30.8% at 6 months. This study highlights that good response rates can be achieved with DLI even after frank relapse in some patients within a cohort where other treatment options are very limited. More prospective studies are warranted to identify the optimal DLI regimen and timing to improve patient outcomes.

The Role of Allogeneic Transplantation in Chronic Myeloid Leukemia in 2023: A Case-Based Concise Review

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of patients, TKIs are not able to control CML. Allogeneic hematopoietic cell transplantation (HCT) has long been a pivotal therapy for CML. At present, allogeneic HCT is considered an option in CML patients diagnosed or progressing to blast phase (BP), for those in chronic phase (CP) resistant to multiple lines of TKI therapy or for those experiencing severe toxicity, mostly hematologic, under TKIs. Moving from real-world cases, we reviewed the results of allogeneic HCT in the setting of advanced-phase CML or failure of TKIs, with a focus on the progresses in transplant technology that has extended transplant options in elderly CML patients and in those lacking a sibling donor, and on the post-HCT strategies for prevention and treatment of disease relapse.

“Like the first time, all over again”: sex, relationships, and risk for relapse to substance use after release from prison

Background Sex, relationships, and substance use often go hand in hand. Despite this, the impact of sex and relationships on recovery are often overlooked in the field of substance use disorder treatment (SUDT). This study aims to explore sex, relationships, and relapse risk for people in recovery and as an overlooked area of importance in SUDT. Method This qualitative study uses semi-structured interviews with people currently and/or formerly in prison, together with ethnographic field data from four high security prisons in Norway, collected between July 2021–April 2022. Results Common sources of anguish around sex after release and recovery included both forming new and maintaining long-term relationships with partners at a different stage in their recovery, dating and initiating sexual relationships with new partners, concerns about sexual performance and fears around attaining sexual pleasure without chemical enhancements. Conclusion The implications that sex, dating and intimate relationships may have for individual relapse to substance use, can and should play a greater role in both SUD treatment and preparation for release from prison. These problems are exacerbated in carceral settings and should be considered when planning re-entry to the community and in the development of individual relapse prevention strategies.

Long-term effectiveness of a nurse-led smoking cessation clinic at a comprehensive cancer center.

Smoking cessation interventions should be promoted in cancer centers to improve clinical outcomes among cancer patients and the quality of life of cancer-free patients and survivors. The aim of the present study was to examine long-term abstinence (1, 3, and 5 years) among smokers who received an intensive nurse-led smoking cessation intervention. A prospective follow-up study was conducted in a smoking cessation clinic in Barcelona. The study included 479 smokers who received a nurse-led smoking cessation intervention that included motivational interviewing, psychological support, behavioral change counseling, promotion of smoke-free policies, and relapse-prevention strategies, as well as pharmacotherapy if necessary, for 12months. We calculated overall and sex-specific 1-, 3-, and 5-year abstinence probabilities (Kaplan-Meier curves) and adjusted hazard ratios (aHRs) of relapse with 95% confidence intervals (CIs) using Cox regression. The overall probability of abstinence at 1 and 5 years was 0.561 (95% CI: 0.516-0.606) and 0.364 (95% CI: 0.311-0.417), respectively. Females had a higher, but not significant, hazard ratio for relapse compared to males (aHR=1.180; 95% CI: 0.905-1.538). Attending <5 visits was the most remarkable determinant of relapsing compared to attending 5-9 visits or ≥10 visits, both overall and by sex (p for trend: overall, p < 0.001; males, p=0.007; and females, p < 0.001). Abstinence probability decreased over the 5-year follow-up but was relatively high. Males had higher abstinence rates than females in all follow-up periods. Completeness of the intensive intervention was the main predictor of cessation. Smoking cessation interventions should consider sex and incorporate strategies to increase adherence to obtain higher long-term abstinence rates.

Electroconvulsive therapy vs Esketamine among patients with Major Depressive Episode

IntroductionMajor depressive disorder is one of the most common and disabling mental disorders. More than 30% of individuals do not achieve remission after several trials of antidepressants and treatment-resistant depression (TRD) is associated with premature mortality. Electroconvulsive therapy (ECT) is considered the gold-standard for TRD treatment,unfortunately it´s underused due to health care barriers and association with adverse cognitive impairment. So, scientists have sought to identify alternative treatments that approach ECT-equivalent efficacy. Trials with Ketamine and more recently with its S-enantiomer (Esketamine) has been made, revealing a rapid and robust antidepressant effect, emerging as an option for TRD treatment.ObjectivesWe we aim to conduct a qualitative review, comparing clinical efficacy, tolerability and acceptability between the use of Esketamine and ECT as a TRD treatment.MethodsWe conduct a non-systematic review of recent evidence between the use of Esketamine and ECT as a TRD treatment, using PubMed/Medline database.ResultsTo compare clinical efficacy, tolerability and acceptability between the use of Esketamine and ECT as a TRD treatment we analyzed outcomes of interest. First,ECT was superior to Esketamine improving depressive symptoms. Comparing suicidal ideation and suicide attempts, most results were not statistically different. About cognition impairment, Esketamine performed better than ECT, particularizing attention, verbal memory, and executive functions; no differences were found for immediate memory or visual memory.About adverse effects Esketamine has less risk of headache and muscle pain, but higher reports of transient, dissociative or depersonalization symptoms, blurred vision, diplopia and nystagmus. An important consideration for clinicians is the comparative tolerability and safety of Esketamine vs ECT; as ECT involves a full dose of anesthesia,it is expected that Esketamine would be better tolerated and safer than ECT. But no study assessed the relative tolerability or acceptability of these different adverse effect profiles.The best strategy for relapse prevention appears to be continuing ECT, continuing pharmacotherapy, or using some combination of both; but Esketamine continuing treatment is effective too.ConclusionsECT may be superior to Esketamine for improving depression severity in the acute phase, but long-term outcomes of these treatments are important to be considered. There are just two studies with long-term follow-up after the trial completed:one found no difference in depression severity during the 3-month follow-up, and the other reported that the remission rates were not different between groups by the 12-month follow-up period.Therefore,future research is needed to further optimize long-term treatment outcomes for both Esketamine and ECT to prevent relapse. Until then,treatment options should be individualized and patient-centered.Disclosure of InterestNone Declared

Heart Rate Variability in Adults With Substance Use Disorder: A Comprehensive Narrative Review.

Heart rate variability (HRV) is an indicator of autonomic abnormalities. However, little is known about the role of HRV related to substance use behavior and the association between the changes in HRV and signs of relapse in substance use. The purpose of this study was to review the existing literature on autonomic response to substance use (i.e., opioids, cocaine, and methamphetamine) measured by HRV and its outcomes related to the risk factors of relapse. A systematic search of the literature was conducted using PubMed, PsychINFO, and Ovid Medline databases. The study includes full-text articles published in English from 2010 to 2020, using measures of HRV in human subjects who use substances. A total of 14 studies were reviewed. Studies included outpatients with a prescription or nonprescription opioid misuse behavior with a primary diagnosis being chronic pain or substance use disorder (SUD). Significantly decreased resting HRV was found in substance users compared to healthy controls. Lower resting HRV has been significantly associated with stress, craving, and greater symptom severities in individuals with SUD and other substance dependence. HRV indices can be potential measures of homeostatic imbalance and self-regulation flexibility. HRV may be a useful tool for monitoring early indication of relapse so that relapse prevention measures can be implemented in a timely manner. Future studies in substance use may benefit from examining HRV in relations to substance use and relapse signs and symptoms in a larger population to guide future relapse prevention strategies.

Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells.

Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 forrelapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. Agreater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse,study of relapse prevention strategies, such as consolidative hematopoietic stemcell transplantation, is critical and warrants further investigation on prospective clinical trials.

Patient perceptions regarding alcohol use after bariatric surgery.

Patients who have undergone bariatric surgery are at increased risk of an alcohol use disorder. Though patients understand this risk, the majority engage in post-surgical alcohol use. This suggests that education alone is not sufficient to reduce post-surgical drinking. To prevent development of post-surgical alcohol use disorders, we need better understanding of the reasons patients use alcohol following surgery. The purpose of this study was to identify factors associated with post-surgical alcohol use. Patients (N = 20) who were 1-3years post-bariatric surgery and were consuming alcohol at least twice monthly participated in a 60-min interview. Participants responded about their knowledge regarding risk of post-surgical alcohol use and reasons why patients may start drinking. Deductive and inductive coding were completed by two independent raters. Although nearly all participants were aware of the risks associated with post-surgical alcohol use, most believed that lifelong abstinence from alcohol was unrealistic. Common reasons identified for using alcohol after bariatric surgery included social gatherings, resuming pre-surgical use, and addiction transfer. Inductive coding identified three themes: participants consumed alcohol in different ways compared to prior to surgery; the effect of alcohol was substantially stronger than pre-surgery; and beliefs about why patients develop problematic alcohol use following surgery. Patients consume alcohol after bariatric surgery for a variety of reasons and they do not believe recommending abstinence is useful. Understanding patient perceptions can inform interventions to minimize alcohol use after bariatric surgery. Modifications to traditional alcohol relapse prevention strategies may provide a more robust solution to decreasing negative outcomes experienced by individuals undergoing bariatric surgery.

A Smartphone Physical Activity App for Patients in Alcohol Treatment: Single-Arm Feasibility Trial.

Alcohol use disorder (AUD) is a significant public health concern worldwide. Alcohol consumption is a leading cause of death in the United States and has a significant negative impact on individuals and society. Relapse following treatment is common, and adjunct intervention approaches to improve alcohol outcomes during early recovery continue to be critical. Interventions focused on increasing physical activity (PA) may improve AUD treatment outcomes. Given the ubiquity of smartphones and activity trackers, integrating this technology into a mobile app may be a feasible, acceptable, and scalable approach for increasing PA in individuals with AUD. This study aims to test the Fit&Sober app developed for patients with AUD. The goals of the app were to facilitate self-monitoring of PA engagement and daily mood and alcohol cravings, increase awareness of immediate benefits of PA on mood and cravings, encourage setting and adjusting PA goals, provide resources and increase knowledge for increasing PA, and serve as a resource for alcohol relapse prevention strategies. To preliminarily test the Fit&Sober app, we conducted an open pilot trial of patients with AUD in early recovery (N=22; 13/22, 59% women; mean age 43.6, SD 11.6 years). At the time of hospital admission, participants drank 72% of the days in the last 3 months, averaging 9 drinks per drinking day. The extent to which the Fit&Sober app was feasible and acceptable among patients with AUD during early recovery was examined. Changes in alcohol consumption, PA, anxiety, depression, alcohol craving, and quality of life were also examined after 12 weeks of app use. Participants reported high levels of satisfaction with the Fit&Sober app. App metadata suggested that participants were still using the app approximately 2.5 days per week by the end of the intervention. Pre-post analyses revealed small-to-moderate effects on increase in PA, from a mean of 5784 (SD 2511) steps per day at baseline to 7236 (SD 3130) steps per day at 12 weeks (Cohen d=0.35). Moderate-to-large effects were observed for increases in percentage of abstinent days (Cohen d=2.17) and quality of life (Cohen d=0.58) as well as decreases in anxiety (Cohen d=-0.71) and depression symptoms (Cohen d=-0.58). The Fit&Sober app is an acceptable and feasible approach for increasing PA in patients with AUD during early recovery. A future randomized controlled trial is necessary to determine the efficacy of the Fit&Sober app for long-term maintenance of PA, ancillary mental health, and alcohol outcomes. If the efficacy of the Fit&Sober app could be established, patients with AUD would have a valuable adjunct to traditional alcohol treatment that can be delivered in any setting and at any time, thereby improving the overall health and well-being of this population. ClinicalTrials.gov NCT02958280; https://www.clinicaltrials.gov/ct2/show/NCT02958280.

Endocannabinoids regulate cocaine-associated memory through brain AEA–CB1R signalling activation

ObjectiveContextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. MethodsWe applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA–CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. ResultsIn the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. ConclusionsTogether, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention.

Estratégias de prevenção de recaída utilizadas por mulheres usuárias de drogas

Qualitative study, developed with 20 female drug users assisted at a Psychosocial Care Center for alcohol and drugs, located in a city in Rio Grande do Sul, Brazil, with the objective of identifying the relapse prevention strategies used by female drug users. Data collection was carried out through audio-recorded individual interviews, following the ethical principles that establish the norms for conducting research involving human beings. For data processing, thematic content analysis was used. Factors such as family, religiosity, and spirituality, animals, plants and music are important strategies for women to prevent relapses to drug use. These strategies proved to be capable of promoting the redefinition of experiences and improved quality of life, in addition to indicating subsidies to health professionals for the planning of actions for women using drugs.

Remaining connected in the age of social distancing: Online strategies for relapse prevention in psychosis

Remaining connected in the age of social distancing: Online strategies for relapse prevention in psychosis