Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma.

BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings. Patients with negative PET findings after two cycles were randomly assigned to continue ABVD (ABVD group) or omit bleomycin (AVD group) in cycles 3 through 6. Those with positive PET findings after two cycles received BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). Radiotherapy was not recommended for patients with negative findings on interim scans. The primary outcome was the difference in the 3-year progression-free survival rate between randomized groups, a noninferiority comparison to exclude a difference of 5 or more percentage points. RESULTS: A total of 1214 patients were registered; 937 of the 1119 patients (83.7%) who underwent an interim PET-CT scan according to protocol had negative findings. With a median follow-up of 41 months, the 3-year progression-free survival rate and overall survival rate in the ABVD group were 85.7% (95% confidence interval [CI], 82.1 to 88.6) and 97.2% (95% CI, 95.1 to 98.4), respectively; the corresponding rates in the AVD group were 84.4% (95% CI, 80.7 to 87.5) and 97.6% (95% CI, 95.6 to 98.7). The absolute difference in the 3-year progression-free survival rate (ABVD minus AVD) was 1.6 percentage points (95% CI, -3.2 to 5.3). Respiratory adverse events were more severe in the ABVD group than in the AVD group. BEACOPP was given to the 172 patients with positive findings on the interim scan, and 74.4% had negative findings on a third PET-CT scan; the 3-year progression-free survival rate was 67.5% and the overall survival rate 87.8%. A total of 62 patients died during the trial (24 from Hodgkin's lymphoma), for a 3-year progression-free survival rate of 82.6% and an overall survival rate of 95.8%. CONCLUSIONS: Although the results fall just short of the specified noninferiority margin, the omission of bleomycin from the ABVD regimen after negative findings on interim PET resulted in a lower incidence of pulmonary toxic effects than with continued ABVD but not significantly lower efficacy. (Funded by Cancer Research UK and Others; ClinicalTrials.gov number, NCT00678327.).

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial.

BACKGROUND: Patients with advanced-stage, low-tumour-burden follicular lymphoma have conventionally undergone watchful waiting until disease progression. We assessed whether rituximab use could delay the need for chemotherapy or radiotherapy compared with watchful waiting and the effect of this strategy on quality of life (QoL). METHODS: Asymptomatic patients (aged ≥18 years) with low-tumour-burden follicular lymphoma (grades 1, 2, and 3a) were randomly assigned centrally (1:1:1), by the minimisation approach stratified by institution, grade, stage, and age, to watchful waiting, rituximab 375 mg/m(2) weekly for 4 weeks (rituximab induction), or rituximab induction followed by a maintenance schedule of 12 further infusions given at 2-monthly intervals for 2 years (maintenance rituximab). On Sept 30, 2007, recruitment into the rituximab induction group was closed and the study was amended to a two-arm study. The primary endpoints were time to start of new treatment and QoL at month 7 (ie, 6 months after completion of rituximab induction). All randomly assigned patients were included in the analysis of time to start of new treatment on an intention-to-treat basis. The main study is now completed and is in long-term follow-up. The study is registered with ClinicalTrials.gov, NCT00112931. FINDINGS: Between Oct 15, 2004, and March 25, 2009, 379 patients from 118 centres in the UK, Australia, New Zealand, Turkey, and Poland were randomly assigned to watchful waiting or maintenance rituximab. 84 patients were recruited to the rituximab induction group before it was closed early. There was a significant difference in the time to start of new treatment, with 46% (95% CI 39-53) of patients in the watchful waiting group not needing treatment at 3 years compared with 88% (83-92) in the maintenance rituximab group (hazard ratio [HR] 0·21, 95% CI 0·14-0·31; p<0·0001). 78% (95% CI 69-87) of patients in the rituximab induction group did not need treatment at 3 years, which was significantly more than in the watchful waiting group (HR 0·35, 95% CI 0·22-0·56; p<0·0001), but no different compared with the maintenance rituximab group (0·75, 0·41-1·34; p=0·33). Compared with the watchful waiting group, patients in the maintenance rituximab group had significant improvements in the Mental Adjustment to Cancer scale score (p=0·0004), and Illness Coping Style score (p=0·0012) between baseline and month 7. Patients in the rituximab induction group did not show improvements in their QoL compared with the watchful waiting group. There were 18 serious adverse events reported in the rituximab groups (four in the rituximab induction group and 14 in the maintenance rituximab group), 12 of which were grade 3 or 4 (five infections, three allergic reactions, and four cases of neutropenia), all of which fully resolved. INTERPRETATION: Rituximab monotherapy should be considered as a treatment option for patients with asymptomatic, advanced-stage, low-tumour-burden follicular lymphoma. FUNDING: Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.

Improving the Use of Subscale-Specific Interventions of the Braden Scale Among Nurses.

BACKGROUND: Pressure injuries (PIs) are costly to hospitals and have a negative impact on patient outcomes. Despite the use of validated tools that describe PI risk, such as the Braden Scale, the incidence of PIs remains high. Studies have shown that Braden Scale subscale scores should be considered when planning care; however, there is a discrepancy between understanding the importance of subscale-specific interventions and implementation. The goal of this study was to test the ability of an educational intervention tailored to specific interventions based on the subscales of the Braden Scale to improve knowledge among nurses. METHOD: This study was a prospective, quasi-experimental, single-group design where nurses (n = 35) from a neurosurgery stepdown unit in a large teaching hospital completed a preintervention survey (T1), attended an educational presentation, and then completed an immediate postintervention survey (T2) and a 2-month postintervention survey (T3). RESULTS: Data analysis compared presurvey scores with postsurvey scores. Nursing comprehension improved from the preintervention survey (T1, M = 5.57) to the postintervention surveys (T2, M = 6.34; T3, M = 6.42) (p = .031). CONCLUSION: Nurses showed increased comprehension after the educational intervention from T1 to T3. [J Contin Educ Nurs. 2024;55(1):42-48.].

Comparing Experiences of Community Reintegration Following Hospitalization Versus Jail Detention During a Mental Health Crisis.

BACKGROUND: This comparative qualitative study explores the experiences of individuals transitioning back to the community after institutionalization following an episode of acute suicidality. METHODS: Semi-structured interviews were conducted with eight individuals who had either been hospitalized (n=4) or incarcerated (n=4) during a mental health crisis that involved acute suicidality. Thematic analysis was conducted first within groups and then between groups. RESULTS: The findings reveal possible disparities in social determinants of mental health, family dynamics, treatment seeking, and coping mechanisms between groups. Social isolation, barriers to socioeconomic stability, and lack of treatment access were all found to be risk factors for poor outcomes during the vulnerable transition period and were experienced by participants in this limited sample. CONCLUSIONS: Individuals transitioning from the hospital after a suicide crisis may benefit from increased family involvement, follow-up, and social support at discharge. After a suicide crisis and incarceration, there is a significant need for housing and employment support to allow for mental health treatment seeking. Future research should build on the proof of concept for comparing the experiences of individuals across institutional settings.

Risk Factors for Self-stigma among Incarcerated Women with Alcohol Use Disorder.

Alcohol use disorder (AUD) is a highly stigmatized condition, often associated with negative stereotypes such as being morally weak, incompetent, unpredictable, and aggressive. People with AUD are at risk of experiencing self-stigma, a social-cognitive experience in which people think others hold negative stereotypes about them, expect to be treated unfairly, and/or believe that negative stereotypes are personally accurate. Women in the criminal justice system with AUD in particular are at risk of experiencing self-stigma due to intersecting sources of disadvantage. Given that self-stigma can lead to treatment avoidance and dropout, it is important to understand risk factors for self-stigma to inform prevention and intervention efforts in the justice system. Incarcerated women with AUD (n=185) completed measures of alcohol self-stigma as well as a variety of theoretically relevant risk factors including sociodemographics, baseline levels of stress and depression, and alcohol-related factors (i.e., length of drinking history, frequency/amount of use, consequences of use, physician advice to stop, belief that legal involvement is related to alcohol use, alcohol-related charges, self-efficacy to quit, readiness for treatment, pressures to enter treatment, factors that influence treatment) and other stigmatized conditions (drug use, exchanging sex, and homelessness). Results showed that experiencing more consequences of alcohol use, pressures to enter treatment, and perceived stress were associated with internalized stigma and anticipated/enacted stigma. This study begins to identify which incarcerated women with AUD are most at risk of experiencing self-stigma that may interfere with alcohol treatment.

2D motility tracking of Pseudomonas putida KT2440 in growth phases using video microscopy.

Pseudomonas putida KT2440 is a gram negative motile soil bacterium important in bioremediation and biotechnology. Thus, it is important to understand its motility characteristics as individuals and in populations. Population characteristics were determined using a modified Gompertz model. Video microscopy and imaging software were utilized to analyze two dimensional (2D) bacteria movement tracks to quantify individual bacteria behavior. It was determined that inoculum density increased the lag time as seeding densities decreased, and that the maximum specific growth rate decreased as seeding densities increased. Average bacterial velocity remained relatively similar throughout the exponential growth phase (~20.9 µm/s), while maximum velocities peak early in the exponential growth phase at a velocity of 51.2 µm/s. P. putida KT2440 also favors smaller turn angles indicating that they often continue in the same direction after a change in flagella rotation throughout the exponential growth phase.

Toxicity of fludarabine and cyclophosphamide with or without rituximab as initial therapy for patients with previously untreated mantle cell lymphoma: results of a randomised phase II study.

The National Cancer Research Network (NCRN) is currently coordinating a Phase III randomised study (LY05) comparing fludarabine and cyclophosphamide (FC) with or without rituximab (R) for previously untreated mantle cell lymphoma (MCL). The combination of FC is well-recognised as significantly immunosuppressive and there are concerns that adding rituximab may increase infection risk further. The impact of rituximab on other markers of toxicity is also unclear. We analysed the toxicity data on 139 patients treated within the NCRN LY05 trial. Non-hematological toxicity was similar between the two treatment arms. The only difference in hematological toxicity was a higher rate of lymphocytopenia with fludarabine cyclophosphamide and rituximab (FCR), which did not translate into increased febrile episodes or infections. In conclusion, the addition of rituximab to FC for previously untreated MCL has no significant impact on toxicity.