bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and mixed-methods synthesis of the experiences, perceptions and attitudes of prison staff regarding adult prisoners who self-harm
Authors: Hewson Thomas , Gutridge Kerry , Bernard Zara , Kay Kathryn , Robinson Louise 
Published: June 2022

Background
Self-harm, including suicide, is common among prisoners. Staff attitudes and perceptions regarding self-harm may affect quality of care and patient safety.

Aims
To systematically review the experiences, perceptions and attitudes of staff in adult prisons regarding self-harm.

Method
Systematic searches of EMBASE, Medline, PsycINFO and CINAHL databases were conducted, and supplemented by hand-searching and grey literature review, to identify relevant English-language articles published since the year 2000. Articles were screened by two authors and evaluated with standardised quality appraisal tools. Qualitative data were analysed thematically, whereas quantitative data were narratively synthesised because of high study heterogeneity.

Results
Two thousand articles were identified, of which 32 were included, involving 6389 participants from five countries. Most studies were moderate (n = 15) or poor (n = 10) quality, and seven were rated as good quality. Staff frequently witnessed self-harm and described multiple perceived risk factors and causes of this. Perceptions that self-harm is ‘manipulative’ or ‘attention-seeking’ were associated with hostility toward prisoners and lower quality of care. Perceived barriers to preventing and managing self-harm included low staffing levels, prison environments and culture, poor staff confidence and insufficient training. The importance of multidisciplinary teamwork and building staff–prisoner relationships were highlighted. Staff occasionally experienced intense psychological reactions to self-harm, which resulted in adaptive or maladaptive coping that influenced their capacity to care.

Conclusions
There are mixed attitudes and perceptions toward self-harm among prison staff. Further training, support and resources are required to protect staff's well-being and improve self-harm prevention and management in prisons.
Racial, ethnic, and socioeconomic survival disparities among children with high-risk neuroblastoma treated on upfront Children’s Oncology Group clinical trials.
Authors: Umaretiya Puja J , Naranjo Arlene , Zhang Fan , Park Julie R. , Weiss Brian D. , Granger Meaghan , DuBois Steven G. , Bagatell Rochelle , Bona Kira 
Published: June 2022

10005 Background: Racial and socioeconomic disparities have not been comprehensively investigated in high-risk neuroblastoma (HR NBL). Prior Children’s Oncology Group (COG) investigations have demonstrated population-based disparities in late relapse rates among Black children, and trial-based disparities in relapse and survival among children living in poverty receiving post-consolidation immunotherapy. It is unknown whether these disparities persist in upfront trials for newly diagnosed patients. We leveraged COG data to investigate race, ethnicity, and socioeconomic disparities in a cohort of children with HR NBL treated on upfront clinical trials from 2007-2016. Methods: Retrospective cohort study of children enrolled on upfront COG HR NBL trials ANBL0532, ANBL09P1, and ANBL12P1. Race and ethnicity were the primary exposures categorized as: Black Non-Hispanic (BNH); Hispanic; Other Non-Hispanic (ONH); or White Non-Hispanic (WNH). Poverty was the secondary exposure, defined as household (public insurance only vs others), area (census-defined high-poverty ZIP code with >20% of population living below 100% Federal Poverty Level (FPL) vs <20% below 100% FPL), and rural (Census-defined rurality measures linked to ZIP code). Overall (OS) and event-free (EFS) survival from time of trial enrollment were plotted by Kaplan-Meier methods; associations with race/ethnicity and poverty were evaluated by log-rank tests. Results: Among 696 children, 16% were BNH, 11% Hispanic, 4% ONH, and 69% WNH. One-third (33%) of children were household poverty-exposed, 26% area poverty-exposed, and 15% rural-exposed. Tumor stage and biology did not differ by race/ethnicity or poverty measures. Five-year OS differed significantly by race/ethnicity (47% Hispanic vs. 50% ONH vs. 61% WNH vs. 62% BNH; p=0.047). Five-year OS was inferior among children exposed to household-poverty (53% vs. 63%; p=0.036) and neighborhood-poverty (54% vs. 62%; p=0.050) compared to unexposed children. There was no difference in OS by rurality. Similar directionality in 5-year EFS outcomes by race/ethnicity and poverty were observed without statistical significance. Conclusions: Race/ethnicity and poverty-exposure are associated with inferior OS outcomes among children with HR NBL despite uniform planned treatment on upfront COG trials. Investigation of mechanisms driving these disparities, including disparate early phase trial enrollment are ongoing to inform targeted health equity interventions to improve outcomes.
Securing access to innovative anticancer therapies for children, adolescents, and young adults outside clinical trials: The SACHA study of the French Society of Pediatric Oncology (SFCE).
Authors: Berlanga Pablo , Ndounga-Diakou Lee Aymar , Corradini Nadege , Ducassou Stephane , Strullu Marion , De Carli Emilie , Andre Nicolas , Entz-Werle Natacha , Defachelles Anne Sophie , Roumy Marianne , Valteau-Couanet Dominique , Gandemer Virginie , Laghouati Salim , Vassal Gilles 
Published: June 2022

10006 Background: Access to innovative anticancer therapies for children, adolescents and young adults within clinical trials in France is steadily increasing in the last years. However, current clinical trials portfolios are still inadequate and thus pediatric hemato-oncologists regularly prescribe innovative medicines outside their marketing authorization, and/or experimental drugs through compassionate use. Methods: The Secured Access to innovative medicines for CHildren with cAncer (SACHA) is a French prospective observational study developed by the French Society of Pediatric Oncology (SFCE) with Gustave Roussy as the legal sponsor to prospectively collect real-world safety and activity data of innovative therapies administered to patients ≤ 25 years-old with pediatric malignancies (solid tumor or leukemia) or other related conditions, either on compassionate use of experimental drugs or off-label use of anti-cancer medicines that have been first approved in adults after 2007. Prior to SACHA inclusion, multicenter tumor board discussion defining best available therapeutic options for each patient with a relapsed malignancy is mandatory. Results: The SACHA study opened in March 2020 and by February 2022, 283 patients have been included from 29/31 SFCE recruiting centers; median age: 11.0 years (range: 0.3-24.4). Main cancer types were central nervous system (CNS) tumors (47%), followed by non-CNS tumors (40%) and leukemias (13%). Innovative therapies prescribed in > 10 patients with reported objective response rate (ORR) and related CTCAE v.5 grade ≥2 clinical and/or grade ≥3 biological adverse drug reactions (ADRs) are described in Table. Conclusions: SACHA confirms the feasibility of this type of prospective real word registry, with a high participation of French centers. Based on this French experience, the Innovative Therapies for Children with Cancer (ITCC) consortium is currently developing a “SACHA International Project” to be opened in ITCC and collaborating countries. [Table: see text]
STRIVE-02: A first-in-human phase 1 trial of systemic B7H3 CAR T cells for children and young adults with relapsed/refractory solid tumors.
Authors: Pinto Navin R. , Albert Catherine Michelle , Taylor Mallory , Wilson Ashley , Rawlings-Rhea Stephanie , Huang Wenjun , Seidel Kristy , Narayanaswany Prabha , Wu Vicky , Brown Christopher , Vitanza Nicholas A. , Orentas Rimas , Gardner Rebecca Alice , Jensen Michael C. , Park Julie R. 
Published: June 2022

10011 Background: B7H3 (CD276) has limited expression in normal tissues and high cell-surface expression in pediatric solid malignancies providing rationale for immunologic therapeutic targeting. We present a first-in-human experience of B7H3 chimeric antigen receptor T cells (CAR-T) for children and young adults (CYA) with relapsed or refractory solid tumors (R/RST). Methods: CYA patients with R/RST were enrolled onto a Phase 1 trial (NCT04483778) to examine the safety of autologous T cells genetically modified to express scFV-IgG4hinge-CD28tm-4-1BB-zeta B7H3-specific CAR with the methotrexate resistance/selection cassette DHFRdm and the tracking/suicide construct EGFRt. All patients received lymphodepleting fludarabine and cyclophosphamide prior to infusion of cryopreserved CAR-T at the prescribed dose level. The maximal tolerated dose or biologically effective dose (BED) was determined based upon observed toxicity through day 28 from initial CAR-T infusion and using a 3+3 statistical design. Results: Sixteen subjects (age 11-24, median 17 years) enrolled and received dose level (DL) 1 (0.5 x 106 CAR-T/kg, n = 3) or DL2 (1 x 106 CAR-T cells/kg, n = 6). No dose limiting toxicity was observed following first infusion, most common toxicities were fatigue and cytokine release syndrome (CRS) (n = 2, maximum CTCAE grade 2). Maximum circulating CAR-T expansion on first infusion was 4.98 cells/uL (range 0.23-4.98 cells/uL) with median persistence of 28 days (range 14-90). Best overall response of Stable Disease was observed in 3 of the 9 subjects infused. Given observed expansion and persistence, DL2 was determined to be the BED. A second infusion at DL2 in one subject demonstrated CAR T expansion to 1590 cells/uL (86% of circulating CD3 cells) with CTCAE grade 2 CRS and transient dose limiting CTCAE grade 4 liver enzyme elevation. A partial metabolic response on FDG-PET by PERCIST criteria was observed in this subject at Day 28. Conclusions: B7H3 CAR T cells are safe and demonstrate anti-tumor activity in CYA with R/RST. CAR-T cell expansion and persistence may be necessary to achieve objective responses. STRIvE-02 Arm B will explore dual expression of CD19 CAR with B7H3 CAR, using lymphocytic CD19 expression to drive CAR expansion and persistence. Clinical trial information: NCT04483778.
Modulation of radiation biomarkers in a randomized phase II study of 131I-MIBG with or without radiation sensitizers for relapsed or refractory neuroblastoma: A report from the NANT Consortium.
Authors: Campbell Kevin M. , Groshen Susan G. , Marachelian Araz , Armant Myriam , Pal Sharmistha , Haas-Kogan Daphne A. , Evans Angela Clare , Coleman Matthew A. , Park Julie R. , Granger Meaghan , Matthay Katherine K. , DuBois Steven G. 
Published: June 2022

10026 Background: 131I-metaiodobenzylguanidine (131I-MIBG) has demonstrated efficacy as a single agent for patients with neuroblastoma. Recent trials have focused on 131I-MIBG combination strategies, though little is known about the impact of combination agents on markers of radiation exposure. Methods: NANT11-01 (NCT02035137) was a multicenter, open label, randomized phase II clinical trial that evaluated 131I-MIBG therapy alone (Arm A) or in combination with vincristine/irinotecan (Arm B) or vorinostat (Arm C) for patients with resistant/relapsed neuroblastoma. We collected blood samples at baseline, 72 hours, 96 hours, and 15 days after 131I-MIBG infusion and determined levels of plasma FLT3 ligand, serum amylase, and gene expression for selected RNA transcripts (apoptosis, DNA damage response and cell cycle related). We evaluated marker association with treatment arm, clinical response using NANT response criteria, toxicity, and whole-body radiation dose. Results: The cohort included 99 patients who had at least one biomarker available for analysis (32 Arm A; 35 Arm B; 32 Arm C). We observed both positive and negative significant modulation in most biomarkers between baseline, 72 hours, and 96 hours following 131I-MIBG. Patients in Arm C had the lowest degree of modulation in FLT3 ligand. Elevated baseline levels of FLT3 ligand were significantly associated with improved Curie response but not overall response. Lower baseline BCL2 levels were associated with higher overall and Curie response. Patients with increased FLT3 ligand at 96 hours after 131I-MIBG therapy were significantly more likely to have grade 4 thrombocytopenia.Peripheral blood gene expression of the BCL2 family of apoptotic markers (BCL2/L1 and BAX) was significantly associated with grade 4 hematological toxicity. Whole-body radiation dose and PRKDC fold change at 72 hours were significantly correlated. No other individual biomarkers were correlated with whole body radiation dose at 72 or 96 hours post 131I-MIBG. Conclusions: Peripheral blood biomarkers relevant to radiation exposure demonstrate significant modulation over time after 131I-MIBG treatment. Biomarkers related to hematopoietic damage and apoptosis were associated with hematological toxicity. Patients treated with vorinostat and 31I-MIBG had differential modulation of FLT3-ligand Further use of these biomarkers may improve our ability to care for patients treated with 131I-MIBG.
Impact of diagnostic and end-of-induction Curie scores in tandem autologous hematopoietic cell transplant for patients with high-risk neuroblastoma: A report from the Children’s Oncology Group.
Authors: Streby Keri A. , Parisi Marguerite T. , Shulkin Barry L. , LaBarre Brian , Bagatell Rochelle , Diller Lisa , Grupp Stephan A. , Matthay Katherine K. , Voss Stephan D. , Yu Alice L. , London Wendy B. , Park Julie R. , Yanik Gregory A. , Naranjo Arlene 
Published: June 2022

10027 Background: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end of induction (EOI) Curie Scores (CS) has been previously described in patients undergoing a single autologous hematopoietic cell transplant (AHCT) as consolidation therapy. We now examine the prognostic significance of CS in patients randomized to tandem or single AHCT on the Children’s Oncology Group (COG) trial ANBL0532. Methods: A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 (n = 652) was performed. Evaluable patients (n = 179) had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either a single (n = 99) or tandem AHCT (n = 80). In addition, evaluable patients had paired mIBG scans at time of initial diagnosis and EOI. Optimal CS cut points maximized the outcome difference (≤ vs > CS cut-off) according to the Youden index. Log-rank tests compared EFS subgroups, with p < 0.05 considered statistically significant. 3-year EFS is presented ± standard error. EFS was estimated for relative reductions in CS of 50% and 75% from diagnosis to EOI. Results: For recipients of tandem AHCT, the optimal cut point at diagnosis was CS = 12, with superior EFS from study enrollment for patients with CS<12 (74.2±7.9%; n = 31) vs CS > 12 (59.2±7.1%; n = 49) (p = 0.002). At EOI, the optimal cut point was CS = 0, with superior EFS from EOI for patients with CS = 0 (72.9±6.4%; n = 48) vs CS > 0 (46.5±9.1%; n = 32) (p = 0.002). The cut point at diagnosis for recipients of single AHCT was CS = 21 (p = 0.04), while the EOI CS had an optimal cut point of 2, but without a significant difference in EFS (p = 0.29). Absolute CS at diagnosis and at EOI had a greater impact on outcome than the relative reduction in CS between diagnosis and EOI, for both single and tandem AHCT. Conclusions: In the setting of tandem transplantation for children with high-risk neuroblastoma, Curie scores at diagnosis and end-induction may identify a more favorable patient group. Patients treated with tandem AHCT who exhibited a CS<12 at diagnosis or CS = 0 at EOI had superior EFS compared to those with CS above these cut points. Similar to prior reports, a CS<2 was the optimal cut point for single transplant recipients. Clinical trial information: NCT00567567.
Phase II trial of gemcitabine and nab-paclitaxel for recurrent osteosarcoma: A report from the National Pediatric Cancer Foundation.
Authors: Wagner Lars M. , Mascarenhas Leo , Isakoff Michael , Setty Bhuvana , Lagmay Joanne P. , Caywood Emi , Sandler Eric Stuart , Pratilas Christine A. , Borinstein Scott C. , Trucco Matteo M. , Fridley Brooke , Reed Damon R. , Oesterheld Javier E. 
Published: June 2022

10042 Background: The combination of gemcitabine and docetaxel is often used to treat patients with recurrent osteosarcoma. A retrospective study of 35 such patients has reported an objective response rate of 17% and 4-month progression-free survival (PFS) of 56% with this combination (BMC Cancer 2016;16:280). Nab-paclitaxel is a nanoparticle taxane that has activity against osteosarcoma xenografts and may have less myelosuppression than docetaxel. The combination of gemcitabine and nab-paclitaxel is now frontline therapy for pancreatic cancer. We conducted a prospective multi-institutional phase II trial of this drug combination for patients with recurrent osteosarcoma. Methods: Patients with relapsed/refractory osteosarcoma with measurable disease and age ≥ 12 years and adequate organ function were included. A Simon’s two-stage design was used to identify a 4-month progression-free survival (PFS) of > 35%. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 weekly x 3 in 4-week cycles. Results: Eighteen patients with a median age 16 years (range 12- 26) received a total of 56 total cycles.(median 2, range 1 - 12). The median number of prior treatment regimens was 3 (range 1-7). Two patients (11%) experienced a partial response, and 6 (33%) received more than 2 cycles. The 4-month PFS was 30% (95% CI 14-62 %). Six patients required dose reductions for neutropenia (n = 4), pleural effusion (1), or neuropathy (1). Two patients were removed from study secondary to neutropenia despite dose reduction and myeloid growth factor support, and one patient came off study due to severe peripheral edema. Conclusions: In this prospective study, the combination of gemcitabine and nab-paclitaxel administered on this schedule showed only limited activity for patients with heavily pretreated recurrent osteosarcoma. Toxicity led to dose modifications in 33% and discontinuation in 17% of patients. When compared to a historical retrospective study, the substitution of nab-paclitaxel for docetaxel did not appear to increase activity or decrease toxicity for this patient population. Clinical trial information: NCT02945800.
The relationship between chronic health conditions and employment transitions among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Bhatt Neel S. , Goodman Pamela J. , Leisenring Wendy M. , Armstrong Gregory T. , Chow Eric Jessen , Hudson Melissa M. , Krull Kevin R. , Nathan Paul C. , Oeffinger Kevin C. , Robison Leslie L. , Kirchhoff Anne C. , Mulrooney Daniel A. 
Published: June 2022

10051 Background: Chronic health conditions are prevalent among adult survivors of childhood cancer. The impact of health on maintaining full-time (FT) employment, a common indicator of socioeconomic independence, has not been studied in this population. Methods: Self-reported employment status (FT, part-time [PT], unemployed [any reason], not in labor force) was assessed at two timepoints (2002-04 [T1] and 2015-16 [T2]) in adult (≥25y old) survivors of childhood cancer diagnosed between 1970-86. Sex-stratified Poisson regression, adjusted for race and ages at diagnosis and T2, was used to study associations between timing and severity of chronic health conditions (graded per the CTCAE v4.03) and transitions from FT to PT or unemployed. Results: Survivors employed FT at T1 (males=1712, median age [min-max]: 34y [25-53]; females=1337, 33y [25-53]) who reported employment status at T2 were included. At T2 (median time from T1 11.5y [9.4-13.8]), 83% males and 70% females remained employed FT, but 4% and 10% transitioned to PT, and 11% and 12% to unemployed (additional 2% and 8% left the labor force), respectively. Male and female survivors with grade 2 or 3-4 neurologic conditions acquired before T1 or between T1-T2 were at a higher risk of moving from FT to PT or unemployed compared to those with grade 0-1 conditions. Males and females with grade 3-4 respiratory conditions prior to T1 and cardiac and musculoskeletal conditions acquired between T1-T2 were also at higher risk for moving to PT or unemployed (Table). Additional predictors for males included grade 2 vision (before T1 RR 2.3, 95% CI 1.5-3.3; between T1-T2 RR 1.7, 95% CI 1.1-2.7) and endocrine (before T1 RR 1.4, 95% CI 1.1-1.9; between T1-T2 RR 1.7, 95% CI 1.3-2.3) conditions. Conclusions: A substantial portion of adult survivors of childhood cancer with health conditions of varying severity leave FT employment. Increased awareness of all stakeholders may facilitate access to clinical counseling and occupational provisions for flexible and supportive work accommodations to reduce work-related barriers for childhood cancer survivors. [Table: see text]
Long-term medical and functional outcomes of medulloblastoma survivors: A population-based, matched cohort study.
Authors: Coltin Hallie , Pequeno Priscila , Liu Ning , Tsang Derek S. , Taylor Michael D. , Bouffet Eric , Nathan Paul C. , Ramaswamy Vijay 
Published: June 2022

10053 Background: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. Methods: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 at <18 years of age in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse/subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse/new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate the cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. We evaluated demographic, disease, and treatment predictors of mortality using Cox proportional hazards models. Results: Of 389 medulloblastoma diagnoses in the study period, 159 (40.9%) were excluded, most commonly due to early death prior to the index date. Two hundred thirty cases were matched to 1150 controls (Table). Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. None of the candidate predictors were significantly associated with mortality on univariate analyses. Conclusions: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions for preventing neurovascular sequelae and hearing loss is warranted, as is dedicated supports for survivors. [Table: see text]