Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Connections Lab: a case study exploring a web-based innovation designed to advance shared risk and protective factor approaches to preventing injuries and violence.

BACKGROUND: Injuries and violence share many of the same risk and protective factors, which are rooted in the social determinants of health (SDOH) and the social determinants of equity. Addressing shared risk and protective factors (SRPFs)-common factors that make it more or less likely that a population will experience injuries or violence-is critical prevention efforts. The Safe States Alliance created the Connections Lab-a suite of web-based resources to help injury and violence prevention public health practitioners and their partners understand, describe, implement and evaluate SRPF approaches. DESIGN: A mixed-methods approach using the Diffusion of Innovation Theory assessed how the Connections Lab influenced users' knowledge, abilities and work related to SRPF approaches. A web-based survey was administered to 234 participants in April-May 2021. Semistructured virtual group discussions were conducted with a subset of 15 survey respondents who volunteered to participate. RESULTS: The case study revealed three key findings. The Connections Lab: was diffused among practitioners across sectors within and outside of public health; it increased practitioners' perceived proficiency across 10 skill sets related to describing, planning, implementing and evaluating SRPF approaches; and it increased understanding of the importance of upstream and structural drivers of injuries and violence. CONCLUSION: The Connections Lab was a critical first step to expand the definition of SRPF approaches, connect SRPFs to concepts of equity and the SDOH, and provide strategies for engaging partners in public health and across other sectors in SRPF approaches.

Securing access to a comprehensive diagnostic panel for children with suspected acute lymphoblastic leukemia: Results from the Mexico in Alliance with St. Jude "Bridge Project".

Background: The "Bridge Project" is a Mexico in Alliance with St. Jude (MAS) initiative developed in 2019 to improve access, accuracy, and timeliness of specialized diagnostic studies for patients with suspected acute lymphoblastic leukemia (ALL). The project strategy relies on service centralization to improve service delivery, biological characterization, risk-group classification, and support proper treatment allocation. Methods: This is an ongoing prospective multisite intersectoral quality improvement (QI) project available to all patients 0-18 years of age presenting with suspected ALL to the 14 actively participating institutions in 12 Mexican states. Institutions send specimens to one centralized laboratory. From a clinical standpoint, the project secures access to a consensus-derived comprehensive diagnostic panel. From a service delivery standpoint, we assess equity, timeliness, effectiveness, and patient-centeredness. From an implementation science standpoint, we document feasibility, utility, and appropriateness of the diagnostic panel and centralized approach. This analysis spans from July 2019 to June 2023. Results: 612 patients have accessed the project. The median age was 6 years (IQR 3-11), and 53% were males. 94% of the specimens arrived within 48 hours, which documents the feasibility of the centralized model, and 100% of the patients received precise and timely diagnostic results, which documents the effectiveness of the approach. Of 505 (82.5%) patients with confirmed ALL, 463/505 (91.6%) had B-cell ALL, and 42/505 (8.3%) had T-cell ALL. High-hyperdiploidy was detected by DNA index in 36.6% and hypodiploidy in 1.6%. 76.6% of the patients had conclusive karyotype results. FISH studies showed t(12;21) in 15%, iAMP21 in 8.5%, t(1;19) in 7.5%, t(4;11) in 4.2%, t(9;22) in 3.2%, del(9)(p21) in 1.8%, and TRA/D (14)(q11.2) rearrangement in 2.4%. Among B-cell ALL patients, 344/403 (85.1%) had Day 15 MRD<1% and 261/305 (85.6%) Day 84 MRD<0.01. For T-cell ALL patients 20/28 (71.4%) had Day 29 MRD<0.01% and 19/22 (86.4%) Day 84 MRD<0.01%. Conclusions: By securing access to a standardized consensus-derived diagnostic panel, the Bridge Project has allowed better characterization of childhood ALL in Mexico while producing unprecedented service improvements and documenting key implementation outcomes. We are using these results to inform iterative changes to the diagnostic panel and an associated treatment guideline (MAS-ALL18).

The role of strength-based parenting, posttraumatic stress, and event exposure on posttraumatic growth in flood survivors.

OBJECTIVE: The present study examined the role of posttraumatic stress symptoms (PTSS), strength-based parenting (SBP), and event exposure on posttraumatic growth (PTG) in Peruvian flood survivors. METHOD: After contacting local authorities, 1,077 adult participants were surveyed 1 year after the flood. Correlation, moderation, and mediation analyses were conducted to determine relationships between variables. RESULTS: Flood survivors experienced both PTSS and PTG. Additionally, event exposure directly facilitated PTG. Further, SBP influenced PTG both directly and by its role in reducing PTSS. Finally, higher levels of SBP aided individuals in converting PTSS into PTG. CONCLUSIONS: Favorable psychological outcomes following floods are not uncommon even for those with high levels of stress or exposure. Individual- and community-level interventions should leverage facilitating factors such as SBP to promote growth outcomes such as PTG. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Rabies Virus Variants Detected from Cougar (Puma concolor) in Mexico 2000-2021.

In 2019, the World Health Organization (WHO) and the Pan-American Health Organization (PAHO) recognized Mexico as a country free of human rabies transmitted by dogs. Nevertheless, the sylvatic cycle remains as a public health concern in the country. Although cougars (Puma concolor) are not reservoirs of any rabies virus variant (RVV), these felines could act as vectors at the top of the food chain, and their relationships with other organisms must be considered important for the regulatory effect on their prey's populations. In this study, genetic and antigenic characterization was performed on all cougar rabies cases diagnosed at the Rabies Laboratory Network of the Ministry of Health (RLNMH) in Mexico from 2000 to 2021. Samples from other species, a skunk, a horse (Equus caballus) (attacked by a cougar), and a gray fox (Urocyon cineroargenteus), were included as reference. Rabies cases in cougars were restricted to two Northern states of Mexico (Sonora and Chihuahua). Five out of six samples of cougars were RVV7 (Arizona gray fox RVV) and one from Sonora was RVV1. Interestingly, there is no evidence of RVV1 in dogs in the Northern states since the 1990s but skunk species now harbor this RVV1 in this region of the country.

States should use Medicaid to support violence intervention efforts.

ABSTRACT: In recent years, calls to address gun violence through public health approaches have increased. However, securing funding for health-based community violence intervention models has remained a challenge. New actions suggest that this may be shifting. Upon taking office, the Biden administration announced a series of funding opportunities for these programs, which ranged from competitive grant programs to a proposed 8-year, $5 billion plan. Less publicized, but just as important, is the administration's announcement that Medicaid can be used to reimburse this work, specifically noting the eligibility of hospital-based violence intervention and prevention programs. For these programs, this creates a predictable and reliable funding source that has not existed to date. This integration of violence prevention programming in the traditional health care and financing systems represents a critical inflection point in the United States' shifting response to community violence. However, the decision to use this optional benefit lies with each state. States should strongly consider harnessing Medicaid as a wise investment to address the United States' gun violence epidemic. LEVEL OF EVIDENCE: Economic and value-based evaluation, level IV.

B,N-Codoped graphene as catalyst for the oxygen reduction reaction: Insights from periodic and cluster DFT calculations.

A comprehensive theoretical study of the oxygen reduction reaction (ORR) over B,N-codoped graphene has been carried out in the framework of DFT using two different approaches based on periodic or cluster models. The comparison and integration of the information provided by the two approaches allow achieving a more complete description of the studied phenomena, combining the advantages of both models. On one hand, the analysis of the structure, stability, and electronic properties of this catalyst permits to identify and characterize the active sites and provides insights into the origin of its high catalytic activity that should be found in the synergistic coupling of the opposite effects of the two B and N heteroatoms used as dopants. On the other hand, the study of the reaction mechanisms evidences that the process is thermodynamically favorable due to the overall high exothermicity, and that the 4e- transfer is the favorite ORR pathway, being the OH hydrogenation the rate-determining step. Overall, all the reported results clearly underline the superior catalytic activity of B,N-codoped graphene toward this reaction. © 2017 Wiley Periodicals, Inc.

[Long term consequences among children exposed to lead poisoning]. / Efectos clínicos a largo plazo en niños intoxicados con plomo en una región del sur de Chile.

BACKGROUND: In 1996 there was a massive lead poisoning in a southern rural community in Chile. The contamination source was a mill whose grinding stone was repaired with lead and contaminated the flour. AIM: To assess the presence of sequelae ten years later, among subjects that were exposed to lead on that occasion. MATERIAL AND METHODS: Cross sectional study of 77 individuals (47 males), aged 10 to 25 years, that were exposed to lead in 1996 and were treated with EDTA. RESULTS: Twenty one percent of subjects had a subnormal intelligence quotient (IQ). The risk of having a low IQ was significantly higher among those exposed before the age of six years. IQ was significantly lower among subjects that, immediately after the exposure, had a lead level over 48 microg/dl, compared with those that had a lead level below 43 microg/dl (86.7+/-7.3 and 93+/-11.6 respectively). No subjects with high blood pressure or evidences of nephrotoxicity were detected. CONCLUSIONS: Subjects aged less than six years at the moment of lead exposure had a lower IQ when assessed ten years later.

Efectos clínicos a largo plazo en niños intoxicados con plomo en una región del sur de Chile / Long term consequences among children exposed to lead poisoning

Background: In 1996 there was a massive lead poisoning in a southern rural community in Chile. The contamination source was a mill whose grinding stone was repaired with lead and contaminated the flour. Aim: To assess the presence of sequelae ten years later, among subjects that were exposed to lead on that occasion. Material and methods: Cross sectional study of 77 individuals (47 males), aged 10 to 25 years, that were exposed to lead in 1996 and were treated with EDTA. Results: Twenty one percent of subjects had a subnormal intellingence quotient (IQ). The risk of having a low IQ was significantly higher among those exposed before the age of six years. IQ was significantly lower among subjects that, immediately after the exposure, had a lead level over 48 fig/dl, compared with those that had a lead level below 43 fig/dl (86.7±7.3 and 93±11.6 respectively). No subjects with high blood pressure or evidences of nephrotoxicity were detected. Conclusions: Subjects aged ¡ess than six years at the moment of lead exposure had a lower IQ when assessed ten years later.