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Abstract This report describes the clinical courses of two acute myeloid leukemia patients. Both had MLL translocations, the first a t(10;11)(p11.2;q23) with MLL-AF10 and the second a t(11;19)(q23;p13.1) with MLL-ELL fusion. They achieved a clinical remission under conventional chemotherapy but relapsed shortly after end of therapy. Both had a history of invasive mycoses (one had possible pulmonary mycosis, one systemic candidiasis). Because no HLA-identical donor was available, a haploidentical transplantation was performed in both cases. Using a specially designed PCR method for the assessment of minimal residual disease (MRD), based on the quantitative detection of the individual chromosomal breakpoint in the MLL gene, both patients achieved complete and persistent molecular remission after transplantation. The immune reconstitution after transplantation is described in terms of total CD3+/CD4+, CD3+/CD8+, CD19+, and CD16+/CD56+ cell numbers over time. The KIR and HLA genotypes of donors and recipients are reported and the possibility of a KIR-mediated alloreactivity is discussed. This report illustrates that haploidentical transplantation may offer a chance of cure without chronic graft-versus-host disease in situations where no suitable HLA-identical donor is available even in a high-risk setting and shows the value of MRD monitoring in the pre- and posttransplant setting.

Abstract Background Abnormalities of 11q23 involving the MLL gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia. Methods Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the CT45A2 gene as novel MLL fusion partner in pediatric acute leukemia. Results Fluorescence in situ hybridization of bone marrow G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the MLL gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing MLL exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the CT45A2 gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the DDX26B gene (exons 9-16) and the entire CT45A1 gene was identified. RNA analysis revealed the presence of a novel MLL-CT45A2 fusion transcript in which the first 9 exons of the MLL gene were fused in-frame to exon 2 of the CT45A2 gene, resulting in a spliced MLL fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE/L1 and SINE/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences. Conclusion We have identified CT45A2 as a novel spliced MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since CT45A2 is the first Cancer/Testis antigen family gene found fused with MLL in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted.

Abstract Background Translocations of the Mixed Lineage Leukemia (MLL) gene occur in a subset (5%) of acute myeloid leukemias (AML), and in mixed phenotype acute leukemias in infancy - a disease with extremely poor prognosis. Animal model systems show that MLL gain of function mutations may contribute to leukemogenesis. Wild-type (wt) MLL possesses histone methyltransferase activity and functions at the level of chromatin organization by affecting the expression of specific target genes. While numerous MLL fusion proteins exert a diverse array of functions, they ultimately serve to induce transcription of specific genes. Hence, acute lymphoblastic leukemias (ALL) with MLL mutations (MLLmu) exhibit characteristic gene expression profiles including high-level expression of HOXA cluster genes. Here, we aimed to relate MLL mutational status and tumor suppressor gene (TSG) methylation/expression in acute leukemia cell lines. Results Using MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification assay), methylation of 24 different TSG was analyzed in 28 MLLmu and MLLwt acute leukemia cell lines. On average, 1.8/24 TSG were methylated in MLLmu AML cells, while 6.2/24 TSG were methylated in MLLwt AML cells. Hypomethylation and expression of the TSG BEX2, IGSF4 and TIMP3 turned out to be characteristic of MLLmu AML cell lines. MLLwt AML cell lines displayed hypermethylated TSG promoters resulting in transcriptional silencing. Demethylating agents and inhibitors of histone deacetylases restored expression of BEX2, IGSF4 and TIMP3, confirming epigenetic silencing of these genes in MLLwt cells. The positive correlation between MLL translocation, TSG hypomethylation and expression suggested that MLL fusion proteins were responsible for dysregulation of TSG expression in MLLmu cells. This concept was supported by our observation that Bex2 mRNA levels in MLL-ENL transgenic mouse cell lines required expression of the MLL fusion gene. Conclusion These results suggest that the conspicuous expression of the TSG BEX2, IGSF4 and TIMP3 in MLLmu AML cell lines is the consequence of altered epigenetic properties of MLL fusion proteins.

Abstract Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases.

Background: The increasing prevalence of child and adolescent overweight and obesity (CAOAO) in Beijing poses significant health and economic challenges. This study assesses the potential health and economic outcomes of implementing specific interventions to address CAOAO in Beijing. Methods: A deterministic Markov cohort model was used to estimate the impact of five interventions from 2025 to 2115: restrictions on unhealthy food marketing to children, mandatory front of package labeling (FOPL), family-based nutrition and exercise education, school-based nutritional health education, and nutritional counseling in primary healthcare. The model evaluated societal costs, healthcare savings, wages, and economic productivity in adulthood, calculating the return on investment (ROI) for each intervention and their combined effect. Result: Without intervention, Beijing is projected to experience a loss of 13.4 million disability-adjusted life years (DALYs) due to CAOAO. The health and economic impact of childhood obesity in Beijing is projected to be CNY 14.6 trillion (USD 2.1 trillion), or a lifetime loss of CNY 6.8 million (USD 0.96 million) per affected child, exceeding the sum of Beijing's GDP from 2021 to 2023. Restrictions on unhealthy food marketing to children and nutrition counseling in primary healthcare are projected to yield the highest returns, with benefits accruing within one year of implementation. Owing to the substantial upfront costs, including personnel, materials, and training, school-based and family-based interventions require a longer time horizon to realize significant health and economic benefits. Conclusions: Effective management of CAOAO in Beijing demands a multifaceted approach. The combination of restrictions on unhealthy food marketing to children, mandatory front of package labeling, nutrition counseling in primary healthcare, school-based intervention, and family-based intervention presents the most substantial health and economic returns. This comprehensive strategy aligns with global best practices and addresses the unique challenges faced by Beijing in combating childhood obesity.

Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic/healthcare factors and use of alloHCT by age group (AYA 15-39y, adult 40-64y, older adult 65-79y) using a linked dataset merging the Center for International Blood and Marrow Transplant Research, California Cancer Registry, and California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within 2 years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYAs (49%). Factors statistically significantly associated with lower alloHCT utilization: (1) AYAs: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; (2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and (3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.

Abstract: Compared with the general population, hematopoietic cell transplantation (HCT) survivors are at elevated risk for developing solid subsequent neoplasms (SNs). The Center for International Blood and Marrow Transplant Research (CIBMTR) is a key resource for quantifying solid SN incidence following HCT, but the completeness of SN ascertainment is uncertain. Within a cohort of 18 450 CIBMTR patients linked to the California Cancer Registry (CCR), we evaluated the completeness of solid SN data reported to the CIBMTR from 1991 to 2018 to understand the implications of using CIBMTR data alone or combined with CCR data to quantify the burden of solid SNs after HCT. We estimated the cumulative incidence of developing a solid SN, accounting for the competing risk of death. Within the cohort, solid SNs were reported among 724 patients; 15.6% of these patients had an SN reported by CIBMTR only, 36.9% by CCR only, and 47.5% by both. The corresponding cumulative incidence of developing a solid SN at 10 years following a first HCT was 4.0% (95% confidence interval [CI], 3.5-4.4) according to CIBMTR data only, 5.3% (95% CI, 4.9-5.9) according to CCR data only, and 6.3% (95% CI, 5.7-6.8) according to both sources combined. The patterns were similar for allogeneic and autologous HCT recipients. Linking detailed HCT information from CIBMTR with comprehensive SN data from cancer registries provides an opportunity to optimize SN ascertainment for informing follow-up care practices and evaluating risk factors in the growing population of HCT survivors., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

To understand transplant center recommendations on return-to-school timing and related support for hematopoietic cell transplant (HCT) survivors, we conducted a two-phase, cross-sectional, web-based survey: In Phase I, medical directors of pediatric HCT centers from the National Marrow Donor Program/ Be The Match Registry were asked regarding the availability of a return to school standardized operating procedure (SOP). In Phase II, HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium were approached to study inter-physician practice variability regarding return to school post-HCT, factors affecting their decision-making, and support provided by HCT centers for return to school. Out of 46 respondents in Phase I (55% response rate), 28 (61%) reported having a SOP. Wide variations in recommendations were noted in 12 received SOPs. In Phase II, 122 physicians (60 centers) responded (30.6% response rate). The majority (60%) recommended autologous HCT recipients return to school within 6 months post-HCT but 65% recommended allogeneic HCT recipients return to school after 6 months or once off immunosuppression. Our findings indicate a lack of consensus within and across HCT centers regarding recommended return to school timing and underscore need for a guideline to standardize this process to ensure patient safety and re-integration into school., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time., Patients and Methods: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n = 29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT., Results: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time., Conclusions: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Adolescent mental health (AMH) needs in England have increased dramatically and needs exceed treatment availability. This study undertook a comparative assessment of the health and economic return on investment (ROI) of interventions to prevent and treat mental disorders among adolescents (10-19 years) and examined intervention affordability and readiness., Methods: Interventions were identified following a review of published and grey literature. A Markov model followed a simulated adolescent cohort to estimate implementation costs and health, education, and economic benefits. Intervention affordability was assessed, comparing annual cost per adolescent with NHS England per capita spending, and an expert panel assessed intervention readiness using a validated framework., Results: Over 10- and 80-year horizons, interventions to treat mild anxiety and mild depression were most cost-effective, with the highest individual lifetime ROI (GBP 5822 GBP 1 and GBP 257: GBP 1). Preventing anxiety and depression was most affordable and 'implementation ready' and offered the highest health and economic benefits. A priority package (anxiety and depression prevention; mild anxiety and mild depression treatment) would avert 5 million disability-adjusted life-years (DALYS) and achieve an ROI of GBP 15: GBP 1 over 10 years or 11.5 million DALYs (ROI of GBP 55: GBP 1) over 80 years., Conclusion: The economic benefits from preventing and treating common adolescent mental disorders equivalent to 25% of NHS England's annual spending in 2021 over 10 years and 91% over 80 years. Preventing and early treatment for anxiety and depression had the highest ROIs and strong implementation readiness., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown. We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the possibility of supplementing the CIBMTR with cancer registry data. This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (allo) or autologous (auto) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018. We analyzed 18,450 patients (alloHCT, n = 8232; autoHCT, n = 10,218). The Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than in CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer versus noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days post-HCT (alloHCT, 31.0%; autoHCT, 54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT, 90.0%; autoHCT, 90.1% versus alloHCT, 47.3%; autoHCT, 82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. The cumulative incidence of cancer-specific mortality at 20 years differed, particularly for alloHCT (CCR, 53.7%; CIBMTR, 27.6%). The median follow-up among alive patients was longer in CCR (alloHCT, 6.0 years; autoHCT, 4.7 years) than in CIBMTR (alloHCT, 5.0 years; autoHCT, 3.8 years). Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that use only death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors., (Copyright © 2023. Published by Elsevier Inc.)

Background: The rapid increase in child and adolescent overweight and obesity (OAO) in China has a significant health and economic impact. This study undertook an investment case analysis to evaluate the health and economic impacts of child and adolescent OAO in China and the potential health and economic returns from implementing specific policies and interventions., Methods: The analysis estimates the reduction in mortality and morbidity from implementing a set of evidence-based interventions across China between 2025 and 2092 using a deterministic Markov cohort model. Modelled interventions were identified by literature review and expert recommendation and include fiscal and regulatory policies, eHealth breastfeeding promotion, school-based interventions, and nutritional counselling by physicians. The study applies a societal costing perspective to model the economic impact on healthcare cost savings, wages, and productivity during adulthood. By projecting and comparing the costs between a status quo scenario and an intervention scenario, the study estimates the return on investment (ROI) for interventions separately and in combination., Findings: Without intervention China will experience 3.3 billion disability-adjusted life years (DALYs) due its current levels of child and adolescent OAO and a lifetime economic impact of CNY 218 trillion (USD 31.6 trillion), or a lifetime CNY 2.5 million loss per affected child or adolescent (USD 350 thousand). National implementation of all five interventions would avert 179.4 million DALYs and result in CNY 13.1 trillion of benefits over the model cohort's lifetime. Implementing fiscal and regulatory policies had the strongest ROI, with benefits accruing at least 10 years after implementation. Scaling up China's current school-based interventions offers China significant health and economic gains, however, the ROI is lower than other modelled interventions., Interpretation: Effective prevention and treatment of child and adolescent OAO is critical to China's health and economic development. Multiple interventions offer a comprehensive approach to address the various factors that increase risk of child and adolescent OAO. Nonetheless, fiscal and regulatory policies offer the strongest health and economic gains., Funding: Funding was provided by UNICEF China., Competing Interests: DCW reports a grant/contract from the World Bank. The rest of the authors declare no competing interests., (© 2023 The Authors.)

Despite efforts to curb the rise in Mexico's child and adolescent overweight and obesity rates, prevalence in Mexico has grown by 120% since 1990 to 43.3% in 2022. This investment case identifies policies that will produce the largest returns for Mexico. The investment case model builds beyond a cost-of-illness analysis by predicting the health and societal economic impact of implementing child and adolescent overweight and obesity interventions in a cohort aged 0-19 from 2025 to 2090. The Markov model's impacts include healthcare expenditures, years of life lost, and reduced wages and productivity. We projected and compared costs in a status quo scenario to an intervention scenario to estimate cost savings and calculate return-on-investment (ROI). Total lifetime health and economic costs amount to USD 1.8 trillion-USD 30 billion on average per year. Implementing five interventions can reduce lifetime costs by approximately 7%. Each intervention has a low cost per disability-adjusted life year averted over 30-year, 50-year, and lifetime horizons. The findings demonstrate that a package of interventions mitigating child and adolescent overweight and obesity offers a strong ROI. The novel investment case methods should be applied to other countries, particularly low- and middle-income countries., (© 2023 UNICEF and The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: To evaluate the association of age with long-term outcome after thrombectomy., Methods: In a retrospective cohort study based on routine healthcare data from Germany between 2010 and 2018, we included 18 506 patients with acute ischaemic stroke treated with mechanical thrombectomy. Association between age and mortality, disability, and level of care at 1 year was assessed., Results: The median age was 76 years, 36.3% were aged ≥80 years and 55.8% were women. Patients aged ≥80 compared with those <80 years had a higher mortality (55.4% vs 28.5%; adjusted HR 1.13; 95% CI 1.05 to 1.31), more often had moderate/severe disability (35.5% vs 33.2%, adjusted HR 1.14; 95% CI 1.06 to 1.23) and less frequently had no/slight disability (17.4% vs 41.0%) at 1 year. Older age was associated with a higher likelihood of living in a nursing home (13.4% vs 9.2%, adjusted HR 1.09; 95% CI 0.97 to 1.22) and a lower likelihood of living at home (33.8% vs 62.8%) at 1 year. These associations were also robust when analysed in patients with no disability prior to stroke. Factors most strongly associated with worse 1-year outcomes in elderly patients were chronic limb-threatening ischaemia (67.9% vs 56.4%; HR 1.59, 95% CI 1.38 to 1.82), dementia at baseline (65.2% vs 47.3%; HR 1.29, 95% CI 1.17 to 1.44) and ventilation >48 hours (79.3% vs 52.2%; HR 2.91, 95% CI 2.66 to 3.18)., Conclusions: In this large 'real-world' cohort, outcomes after mechanical thrombectomy were strongly associated with age. Of patients aged ≥80 years more than half were dead and less than one-fifth were functionally independent at 1 year. Certain comorbidities and ventilation >48 hours were associated with even worse outcomes., Competing Interests: Competing interests: CB has received speaking fees from Chugai Pharma. HW receives honoraria for acting as a member of Scientific Advisory Boards from Abbvie, Alexion, Argenx, Bristol Myers Squibb/Celgene, Janssen, Merck, Novartis and Sandoz. Speaker honoraria and travel support from Alexion, Biogen, Bristol Myers Squibb, Genzyme, Merck, Neurodiem, Novartis, Ology, Roche, TEVA and WebMD Global. HW is acting as a paid consultant for Abbvie, Actelion, Argenx, BD, Biogen, Bristol Myers Squibb, EMD Serono, Fondazione Cariplo, Gossamer Bio, Idorsia, Immunic, Immunovant. Janssen. Lundbeck, Merck, NexGen, Novartis, PSI CROl, Roche, Sanofi, Swiss Multiple Sclerosis Society, UCB and Worldwide Clinical Trials. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutsche Myasthenie Gesellschaft e.V., Alexion. Amicus Therapeutics Inc., Argenx, Biogen, CSL Behring, F. Hoffmann - La Roche, Genzyme, Merck KgaA, Novartis, Roche Pharma and UCB Biopharma. HR received Consulting fees from PLURISTEM, NEOVASC; Payment honoraria for lectures, presentations from DAICHI SANKYIO, DIAPLAN, MEDUPDATE, STREAMEDUP, CORVIA; Participation in Advisory Boards from BMS, PFIZER, NOVONORDISK; the department received research grants from BARD, PFIZER, BMS. JM has received grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung (BMBF), Else Kröner-Fresenius-Stiftung, EVER Pharma Jena, and Ferrer International, travel grants from Boehringer Ingelheim, and speaking fees from Bayer Vital and Chugai Pharma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The treatment of malignant and nonmalignant hematologic disorders continues to benefit from significant scientific advancement and progress in the use of hematopoietic cell transplantation and cellular therapies. However, barriers associated with receiving these lifesaving treatments and care remain, which necessitate innovative approaches to overcome, so all persons in need can receive these therapies. This article reviews barriers to receiving hematopoietic cell transplantation and cellular therapies, and highlights novel approaches taken by the National Marrow Donor Program in reducing barriers for all patients in need., Competing Interests: Declaration of competing interest All authors have no conflict of interest to disclose relevant to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We explored how sexting (no sexting, sent only, received only, reciprocal) was associated with depression, anxiety, sleep problems, and compulsive sexual behaviors across sex and sexual identity groups. We also examined how substance use predicted sexting classifications. Data came from 2,160 college students living in the United States. Results indicated that 76.6 percent of the sample had engaged in sexting (primarily reciprocal). Participants who had engaged in sexting generally evidenced higher depression, anxiety, sleep problems, and compulsive sexual behaviors. Effect sizes were largest on compulsive sexual behavior indicators. Marijuana use was the only significant substance use predictor of reciprocal and "received only" sexting compared with no sexting. Illicit substance use (e.g., cocaine) was low base rate but descriptively was associated with sexting. Compulsive sexual behavior remained a robust positive correlate of sexting compared with non-sexting participants regardless of sex and sexual identity. Most other mental health indicators became nonsignificant correlates of sexting in nonheterosexual participants and were weak positive correlates in heterosexual participants. Marijuana use remained the only significant substance use predictor of reciprocal and "received only" sexting when adjusted for sex and sexual identity. We conclude that sexting is only weakly associated with depression, anxiety, and sleep problems but robustly associated with compulsive sexuality and marijuana use. These findings do not appear to vary meaningfully on the basis of sex or sexual identity, with the exception that the effect sizes between sexting and compulsive sexual behaviors were much stronger for females compared with males (regardless of sexual identity).

Introduction: Due to the COVID-19 pandemic, healthcare centers quickly adapted services into virtual formats. Pain clinics in Canada play a vital role in helping people living with pain, and these clinics remained essential services for patients throughout the pandemic. This study aimed to (1) describe and compare the transition from in-person to virtual pain care services at Canadian pain clinics during the onset of the COVID-19 pandemic and (2) provide postpandemic recommendations for pain care services to optimize the quality of patient care., Materials and Methods: We used a qualitative participatory action study design that included a cross-sectional survey for data collection and descriptive analysis to summarize the findings. Survey responses were collected between January and March of 2021. The survey was administered to the leadership teams of 11 adult pain clinics affiliated with the Chronic Pain Centre of Excellence for Canadian Veterans. Responses were analyzed qualitatively to describe the transition to the virtual pain services at pain clinics., Results: We achieved a 100% response rate from participating clinics. The results focus on describing the transition to the virtual care, current treatment and services, the quality of care, program sustainability, barriers to maintaining virtual services, and future considerations., Conclusions: Participating clinics were capable of transitioning pain care services to the virtual formats and have in-person care when needed with proper safety precautions. The pandemic demonstrated that it is feasible and sustainable for pain clinics to have a hybrid of virtual and in-person care to treat those living with pain. It is recommended that moving forward, there should be a hybrid of both virtual and in-person care for pain clinics. Ministries of Health should continue to develop policies and funding mechanisms that support innovations aimed at holistic healthcare, interdisciplinary teams, and the expansion of clinics' geographical reach for patient access., Competing Interests: The clinics that participated and the researchers of this study are affiliated with the CPCoE at the time this study was conducted. The authors declare that they have no conflicts of interest., (Copyright © 2023 Victoria Borg Debono et al.)

Background: Child and adolescent overweight and obesity rates are increasing rapidly, notably in middle-income countries (MICs). Effective policy adoption has been limited in low-income and middle-income countries. To respond, investment cases were developed in Mexico, Peru, and China to understand the health and economic returns on investment in childhood and adolescent overweight and obesity interventions., Methods: The investment case model applied a societal perspective to predict the health and economic impact of childhood and adolescent overweight and obesity in a cohort aged 0-19 years, beginning in 2025. Impacts include health-care expenditures, years of life lost, reduced wages, and productivity. Unit cost data from the literature was used to develop a status quo scenario over the model cohort's average expected lifetime period (2025-90 in Mexico; 2025-92 in China and Peru) and was compared with an intervention scenario to estimate cost savings and calculate return on investment (ROI). Effective interventions were identified from the literature and selected to reflect country-specific prioritization after stakeholder discussions. Priority interventions range from fiscal policies, social marketing, breastfeeding promotion, school-based policies, and nutritional counselling., Findings: Total predicted lifetime health and economic impacts of child and adolescent overweight and obesity in the three countries ranged from US$1·8 trillion in Mexico, $211 billion in Peru, and $33 trillion in China. Implementing a set of priority interventions in each country could reduce lifetime costs by $124 billion (Mexico), $14 billion (Peru), and $2 trillion (China). Implementing a unique package of interventions for each country resulted in a predicted lifetime ROI of $515 per $1 invested in Mexico, $164 per $1 in Peru, and $75 per $1 in China. Fiscal policies were very cost-effective and had positive ROIs in all three countries for 30-year, 50-year, and lifetime time horizons until 2090 (Mexico) or 2092 (China and Peru). Although school interventions had a positive ROI in all countries across a lifetime horizon, relatively they yielded considerably lower ROIs than other interventions evaluated., Interpretation: Lifetime health and economic impacts of child and adolescent overweight and obesity across the three MICs are high and will undermine countries' ability to meet sustainable development goals. Investing in nationally relevant cost-effective interventions could reduce lifetime costs., Funding: UNICEF, partly supported by a grant from Novo Nordisk., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Advances in hematopoietic cell transplantation (HCT) have substantially improved patient survival, increasing the importance of studying outcomes and long-term adverse effects in the rapidly growing population of HCT survivors. Large-scale registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) are a valuable resource for studying mortality and late effects after HCT, providing detailed data reported by HCT centers on transplantation-related factors and key outcomes. This study was conducted to evaluate the robustness of CIBMTR outcome data and assess health-related outcomes and healthcare utilization among HCT recipients. We linked data from the CIBMTR for California residents with data from the population-based California Cancer Registry (CCR) and hospitalization information from the California Patient Discharge Database (PDD). In this retrospective cohort study, probabilistic and deterministic record linkage used key patient identifiers, such as Social Security number, ZIP code, sex, birth date, hematologic malignancy type and diagnosis date, and HCT type and date. Among 22,733 patients registered with the CIBMTR who underwent autologous or allogeneic HCT for hematologic malignancy between 1991 and 2016, 89.0% were matched to the CCR and/or PDD (n = 17,707 [77.9%] for both, n = 1179 [5.2%] for the CCR only, and n = 1342 [5.9%] for the PDD only). Unmatched patients were slightly more likely to have undergone a first autologous HCT than an allogeneic HCT (12.6% versus 9.0%), to have a larger number of missing linkage identifiers, and to have undergone HCT prior to 2010. Among the patients reported to the CIBMTR who matched to the CCR, 85.7% demonstrated concordance of both hematologic malignancy type and diagnosis date across data sources. This linkage presents unparalleled opportunities to advance our understanding of HCT practices and patient outcomes., Competing Interests: Conflict of interest statement There are no conflicts of interest to report., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

Allogeneic hematopoietic cell transplantation (alloHCT) is a resource-intensive procedure and the sole potentially curative treatment available for patients with acute myelogenous leukemia (AML). Although Medicare coverage may help address a major financial barrier to accessing alloHCT, there remains an unmet need for alloHCT owing to sociodemographic disparities. This study examined trends and factors associated with the utilization of alloHCT and the estimated unmet need for alloHCT among Medicare beneficiaries with AML. This retrospective cohort study included patients (age 65 to 74 years) with a diagnosis of AML identified in Medicare claims data from 2010 through 2016. To study trends in utilization, transplantation rates were calculated as the number of patients who underwent alloHCT within 180 days and 1 year of diagnosis (numerator) divided by the total number of patients with AML within each diagnosis year (denominator). A multivariable logistic regression was used to identify factors associated with the likelihood of undergoing alloHCT within 1 year of diagnosis. Two approaches were applied to estimate the unmet need for alloHCT. The first approach used claims data to identify the potential need for alloHCT among patients who achieved complete remission for at least 90 days. The second approach used established National Marrow Donor Program (NMDP) methodology, which considers estimates of risk level, response to treatment, comorbidity, and early mortality, to identify the potential and unmet need for alloHCT. The overall estimated need and unmet need from 2010 to 2015 and over different time periods were evaluated for both approaches. The alloHCT rate within 180 days of diagnosis increased from 8% in 2010 to 15.8% in 2016 (P < .001), and the 1-year alloHCT rate also increased over time, from 11.9% in 2010 to 20.0% in 2015 (P < .001). The likelihood of undergoing alloHCT within 1 year of diagnosis was associated with diagnosis year, age, race, geographic region, Elixhauser Comorbidity Index, and population-level median household income. Between 2010 and 2015, the claims data approach estimated a lower potential need for alloHCT compared with the NMDP methodology estimate (27% versus 36%); both approaches estimated that 43% to 44% of patients with a potential need for alloHCT had an unmet treatment need. Despite the differences in estimated potential need between the 2 approaches, both showed a sustained unmet need but with a downward trend over time. Our data show that utilization of alloHCT has increased over time among Medicare beneficiaries with AML. Two approaches of need analysis were conducted for validation of estimated need and unmet need for alloHCT using claim-identified remission status, given the lack of cytogenetics and molecular information in claims data. Both approaches to estimating the unmet need for alloHCT found a downward trend over time; however, there are differences in utilization of alloHCT by age, race, geographic region, comorbidity, and socioeconomic status, indicating disparities in access to alloHCT among Medicare beneficiaries with AML. This suggests the need for policy efforts, research, and continued education to improve access to alloHCT and to close the gap between the actual utilization of alloHCT and the unmet need., Competing Interests: Conflict of interest statement There are no conflicts of interest to report., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Access to adequate dental services is limited for children in rural communities in the United States.The purpose of this paper was to describe how two school-based teledentistry programs increased access to oral health services for children and adolescents living in rural areas. Methods: The School-Based Telehealth Network Grant Program (SB TNGP) was designed to expand access to, and improve the quality of health care services in schools through telehealth. Data were collected from July 1 to December 31, 2019 on 164 students at 7 preschool sites by Marshfield Clinic Health System (MCHS) and on 1,467 students at 57 school sites by Children's Dental Services (CDS). Results: Both MCHS and CDS reported that over 99 percent of encounters were successfully completed using telehealth technology. Both grantees reported that 99.4 percent of students received an oral health evaluation/screening, primarily through a dental hygienist traveling to the school site connected to a dentist or advanced dental therapist through telehealth. One half of the students had dental caries (50.6 % MCHS; 48.6% CDS). Both grantees referred all students with dental caries for oral health follow-up care. Conclusions: By utilizing dental hygienists traveling to school sites and connecting with centrally located dental professionals through telehealth, both grantees increased access to needed oral health care services for rural children. Oral health screening in school settings using dental hygienists with teledentistry can provide an efficient way to identify students at high risk for dental caries and offer a valuable strategy for oral disease prevention and control., (Copyright © 2022 The American Dental Hygienists’ Association.)

Background: Mobile health (mhealth) technology presents an opportunity to address many unique challenges refugee populations face when accessing healthcare. A robust body of evidence supports the use of mobile phone-based reminder platforms to increase timely and comprehensive access to health services. Yet, there is a dearth of research in their development for displaced populations, as well as refugee perspectives in design processes to improve effective adoptions of mhealth interventions., Objective: This study aimed to explore healthcare barriers faced by Syrian refugee women in Turkey, and their perceptions of a maternal-child health mobile application designed to provide antenatal care and vaccine services. These findings guided development of a framework for enhancing acceptability of mobile health applications specific to refugee end-users., Methods: Syrian refugee women who were pregnant or had at least one child under the age of 2 years old at the time of recruitment ( n = 14) participated in semi-structured in-depth interviews. Participants had the opportunity to directly interact with an operational maternal-child health mobile application during the interview. Using a grounded theory approach, we identified critical factors and qualities mhealth developers should consider when developing user-friendly applications for refugees., Results: It was observed that a refugee's perception of the mobile health application's usability was heavily influenced by past healthcare experiences and the contextual challenges they face while accessing healthcare. The in-depth interviews with refugee end-users identified that data security, offline capability, clear-user directions, and data retrievability were critical qualities to build into mobile health applications. Among the features included in the maternal-child health application, participants most valued the childhood vaccination reminder and health information features. Furthermore, the application's multi-lingual modes (Arabic, Turkish, and English) strengthened the application's usability among Syrian refugee populations living in Turkey., Conclusions: The inclusion of refugee perceptions in mhealth applications offers unique developer insights for building more inclusive and effective tools for vulnerable populations. Basic upfront discussions of the mobile application's health goals and its personal value to the user may improve their long-term use. Further prospective research is needed on retention and use of mobile health applications for refugee women and other displaced populations., Competing Interests: Authors AS and NN are founders of HERA Digital Health, a non-profit that created HERA App, the described open source mhealth intervention. Neither receive funding or compensation for this role. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meyer, Surmeli, Hoeflin Hana and Narla.)

Armenia's health spending is characterized by low public spending and high out-of-pocket expenditure (OOP), which not only poses a financial barrier to accessing healthcare for Armenians but can also impoverish them. We analyzed Armenia's Integrated Living Conditions Surveys 2014-2018 data to assess the incidence and correlates of catastrophic health expenditure (CHE) and impoverishment. Households were considered to have incurred CHE if their annual OOP exceeded 40 percent of the per capita annual household non-food expenditure. We assessed impoverishment using the US$1.90 per person per-day international poverty line and the US$5.50 per person per-day upper-middle-income country poverty line. Logistic regression models were fitted to assess the correlates of CHE and impoverishment. We found that the incidence of CHE peaked in 2017 before declining in 2018. Impoverishment decreased until 2017 before rising in 2018. After adjusting for sociodemographic factors, households were more likely to incur CHE if the household head was older than 34 years, located in urban areas, had at least one disabled member, and had at least one member with hypertension. Households with at least one hypertensive member or who resided in urban areas were more likely to be impoverished due to OOP. Paid employment and high socioeconomic status were protective against both CHE and impoverishment from OOP. This detailed analysis offers a nuanced insight into the trends in Armenia's financial risk protection against catastrophic and impoverishing health expenditures, and the groups predominantly affected. The incidence of CHE and impoverishment in Armenia remains high with a higher incidence among vulnerable groups, including those living with chronic disease, disability, and the unemployed. Armenia should consider different mechanisms such as subsidizing medication and hospitalization costs for the poorest to alleviate the burden of OOP., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kazungu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Administrative claims data provide real-world service utilization of acute myeloid leukemia (AML) treatment, but lacks insight into treatment delays or barriers. The National Marrow Donor Program (NMDP)/Be The Match Search (Search) data contains information on donor search, but lacks information on treatment received if allogeneic hematopoietic cell transplant (HCT) is not performed. We hypothesized that linking these two data sets would create a rich resource to define factors associated with receiving HCT that could not be evaluated with either data set alone., Methods: A subset of 2010-2016 Medicare administrative claims data was linked with Search data. A total of 5,351 patients with AML age 65-74 years (HCT = 607, no HCT = 4,744) were identified using Medicare. These patients were then linked to 93,800 records with a donor search between 2009 and 2016. Patient date of birth, sex, disease, ZIP code, transplant center/hospital, and diagnosis date were used for matching. Exploratory analysis was conducted to identify predictors associated with receiving HCT for patients with AML who received a search., Results: The data sets were successfully linked, showing high sensitivity and specificity. The final cohort included 5,085 patients with AML (HCT = 533, no HCT = 4,552). Of 97 patients who received HCT without a matched search, more than 85% received a related donor HCT. Of those not receiving HCT, 609 had a matched NMDP search and 3,943 did not have a matched NMDP search. Multivariate analysis showed time to search, age, diagnosis year, race/ethnicity, and neighborhood education status associated with receiving HCT., Conclusion: Methods herein demonstrate the feasibility of linking Search and Medicare data. Similar methods may be applied to answer critical questions regarding barriers to HCT, thereby identifying areas to improve access to care.

This study aimed to determine whether a geriatrics-focused hospitalist trauma comanagement program improves quality of care. A pre-/post-implementation study compared older adult trauma patients who were comanaged by a hospitalist with those prior to comanagement at a level 1 trauma center. One-to-one propensity score matching was performed based on age, gender, Injury Severity Score, comorbidity index, and critical illness on admission. Outcomes included orders for geriatrics-focused quality indicators, as well as hospital mortality and length of stay. Wilcoxon rank-sum test (continuous variables) and chi-square or Fisher exact test (categorical variables) were used to assess differences. Propensity score matching resulted in 290 matched pairs. The intervention group had decreased use of restraints (P = 0.04) and acetaminophen (P = 0.01), and earlier physical therapy (P = 0.01). Three patients died in the intervention group compared with 14 in the control (P = 0.0068). This study highlights that a geriatrics-focused hospitalist trauma comanagement program improves quality of care., (Copyright © 2021 the American College of Medical Quality.)

Hospitalization is common among older adults. Prolonged time in bed during hospitalization can lead to deconditioning and functional impairments. Our team is currently working with Department of Veterans Affairs (VA) medical centers across the United States to implement STRIDE (assiSTed eaRly mobIlity for hospitalizeD older vEterans), a hospital-based walking program designed to mitigate the risks of immobility during hospitalization. However, the COVID-19 pandemic made in-person, or face-to-face, walking challenging due to social distancing recommendations and infection control concerns. In response, our team applied principles of implementation science, including stakeholder engagement, prototype development and refinement, and rapid dissemination and feedback, to create STRIDE in Your Room (SiYR). Consisting of self-guided exercises, light exercise equipment (e.g., TheraBands, stress ball, foam blocks, pedometer), the SiYR program provided safe alternative activities when face-to-face walking was not available during the pandemic. We describe the methods used in developing the SiYR program; present feedback from participating sites; and share initial implementation experiences, lessons learned, and future directions.

Objectives: The primary objective of this study was to predict healthcare cost trajectories for patients with newly diagnosed acute myeloid leukemia (AML) receiving allogeneic hematopoietic cell transplantation (alloHCT), as a function of days since chemotherapy initiation, days relative to alloHCT, and days before death or last date of insurance eligibility (LDE). An exploratory objective examined patients with AML receiving chemotherapy only., Methods: We used Optum's de-identified Clinformatics ® Data Mart Database to construct cumulative cost trajectories from chemotherapy initiation to death or LDE (through 31 December 2014) for US patients aged 20-74 years diagnosed between 1 March 2004 and 31 December 2013 (n = 187 alloHCT; n = 253 chemotherapy only). We used generalized additive modeling (GAM) to predict expected trajectories and bootstrapped confidence intervals (CIs) at user-specified intervals conditional on dates of alloHCT and death or LDE relative to chemotherapy initiation., Results: Expected costs (in 2017 values) for a hypothetical patient receiving alloHCT 60 days after chemotherapy initiation and followed for 5 years were $US572,000 (95% CI 517,000-633,000); $US119,000 (95% CI 51,000-192,000); $US102,000 (95% CI 0-285,000); $US79,000 (95% CI 0-233,000), for years 1-4, respectively, and either $US494,000 (95% CI 212,000-799,000) or $US108,000 (95% CI 0-230,000) in year 5, whether the patient died or was lost to follow-up on day 1825, respectively., Conclusions: Rates of cost accrual varied over time since chemotherapy initiation, with accelerations around the time of alloHCT and death. GAM is a potentially useful approach for imputing longitudinal costs relative to treatment initiation and one or more intercurrent, clinical, or terminal events in randomized controlled trials or registries with unrecorded costs or for dynamic decision-analytic models.

Autologous hematopoietic stem cell transplantation (auto-HCT) is a complex procedure that can be performed in both inpatient (IP) and outpatient (OP) care settings. We examined reimbursement, service utilization, and patient financial responsibility among Medicare beneficiaries with multiple myeloma who underwent auto-HCT in the IP and OP settings using a merged dataset of the Center for International Blood and Marrow Transplant Research observational database and Centers for Medicare & Medicaid Services Medicare administrative claims data. Selection criteria included first auto-HCT, time from diagnosis to auto-HCT <18 months, and continuous enrollment in Medicare Parts A and B for 30 days before HCT index claims and 100 days post-HCT or until death. Total reimbursement and patient responsibility were adjusted for patient and disease characteristics using a weighted generalized linear model. The final cohort comprised 1640 patients, 1445 (88%) who received IP-HCT and 195 (12%) who received OP-HCT. The adjusted total mean reimbursement was higher for IP-HCT compared with OP-HCT ($82,368 [95% CI, $77,643 to $87,381] versus $46,824 [95% CI, $43,567-$50,325]; P < .0001). Adjusted total mean patient responsibility was $4736 for IP-HCT (95% CI, $4731 to $5133) and $6944 for OP-HCT (95% CI, $6296 to $7658) (P < .0001). Within 100 days post-HCT, 107 of the 195 OP-HCT recipients (55%) had at least 1 subsequent admission, compared with 348 of the 1445 IP-HCT recipients (24%). Reimbursement, service utilization, and financial responsibility varied by HCT setting. As the number of Medicare beneficiaries who undergo auto-HCT increases, coverage policy needs to consider how location of services leads to variations in the financial burden for both hospital systems and patients., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The primary aim of this study was to describe healthcare costs and utilization during the first year after a diagnosis of acute myeloid leukemia (AML) for privately insured non-Medicare patients in the United States aged 50 to 64 years who were treated with either chemotherapy or chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT). MarketScan (Truven Health Analytics) adjudicated total payments for inpatient, outpatient, and prescription drug claims from 2007 to 2011 were used to estimate costs from the health system perspective. Stabilized inverse propensity score weights were constructed using logistic regression to account for differential selection of alloHCT over chemotherapy. Weighted generalized linear models adjusted costs and utilization (hospitalizations, inpatient days, and outpatient visit-days) for differences in age, sex, diagnosis year, region, insurance plan type, Elixhauser Comorbidity Index), and 60-day prediagnosis costs. Because mortality data were not available, models could not be adjusted for survival times. Among 29,915 patients with a primary diagnosis of AML, 985 patients met inclusion criteria (774 [79%] receiving chemotherapy alone and 211 [21%] alloHCT). Adjusted mean 1-year costs were $280,788 for chemotherapy and $544,178 for alloHCT. Patients receiving chemotherapy alone had a mean of 4 hospitalizations, 52.9 inpatient days, and 52.4 outpatient visits in the year after AML diagnosis; patients receiving alloHCT had 5 hospitalizations, 92.5 inpatient days, and 74.5 outpatient visits. Treating AML in the first year after diagnosis incurs substantial healthcare costs and utilization with chemotherapy alone and with alloHCT. Our analysis informs healthcare providers, policymakers, and payers so they can better understand treatment costs and utilization for privately insured patients aged 50 to 64 with AML., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Our objective was to evaluate the impact of a dedicated resuscitation and stabilization (RAS) room and process changes on infant stabilization time., Study Design: A prospective quality improvement study was conducted on preterm infants in a tertiary care center. A dedicated RAS room, preresuscitation huddle, infant-isolette-ventilator pairing and improved documentation were implemented. The primary outcome was median time to stabilization and secondary outcomes were illness severity on day 1 and morbidity at discharge., Results: A sustained reduction in median time to stabilization from 90 min in the preimplementation phase to 72 min in the sustainability phase was observed. All planned and iterative process changes were integrated into the RAS team's daily routine. Time to completion of procedures decreased, illness severity and morbidity remained unchanged., Conclusion: A dedicated RAS room adjacent to the delivery suite in conjunction with process changes improves efficiency of care.

Background: Growth of neonatal intensive care units in number and size has raised questions towards ability to maintain continuity and quality of care. Structural organization of intensive care units is known as a key element for maintaining the quality of care of these fragile patients. The reconstruction of megaunits of intensive care to smaller care units within a single operational service might help with provision of safe and effective care., Methods/design: The clinical team and patient distribution lay out, admission and discharge criteria and interdisciplinary round model was reorganized to follow the microstructure philosophy. A working group met weekly to formulate the implementation planning, to review the adaptation and adjustment process and to ascertain the quality of implementation following the initiation of the microsystem model., Discussion: In depth examination of microsystem model of care in this study, provides systematic evaluation of this model on variable aspects of health care. The individual projects of this trial can be source of solid evidence for guidance of future decisions on optimized model of care for the critically ill newborns., Trial Registration: ClinicalTrial.gov, NCT02912780 . Retrospectively registered on 22 September 2016.

As a drastic environmental change, metal pollution may promote the rapid evolution of genetic adaptations contributing to metal tolerance. In Arabidopsis halleri, genetic bases of zinc (Zn) and cadmium (Cd) tolerance have been uncovered only in a metallicolous accession, although tolerance is species-wide. The genetic determinants of Zn and Cd tolerance in a nonmetallicolous accession were thus investigated for the first time. The genetic architecture of tolerance was investigated in a nonmetallicolous population (SK2) by using first backcross progeny obtained from crosses between SK2 and Arabidopsis lyrata petraea, a nonmetallophyte species. Only one significant and common quantitative trait locus (QTL) region was identified explaining 22.6% and 31.2% of the phenotypic variation for Zn and Cd tolerance, respectively. This QTL co-localized with HEAVY METAL ATPASE 4 (AhHMA4), which was previously validated as a determinant of Zn and Cd tolerance in a metallicolous accession. Triplication and high expression of HMA4 were confirmed in SK2. In contrast, gene duplication and high expression of METAL TOLERANT PROTEIN 1A (MTP1A), which was previously associated with Zn tolerance in a metallicolous accession, were not observed in SK2. Overall, the results support the role of HMA4 in tolerance capacities of A. halleri that may have pre-existed in nonmetallicolous populations before colonization of metal-polluted habitats. Preadaptation to metal-contaminated sites is thus discussed., (© 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.)

There is an increasing need for the development of approaches to measure quality, costs, and resource utilization patterns among allogeneic hematopoietic cell transplantation (HCT) patients. Administrative claims data provide an opportunity to examine service utilization and costs, particularly from the payer's perspective. However, because administrative claims data are primarily designed for reimbursement purposes, challenges arise when using it for research. We use a case study with data derived from the 2007 to 2011 Truven Health MarketScan Research database to discuss opportunities and challenges for the use of administrative claims data to examine the costs and service utilization of allogeneic HCT and chemotherapy alone for patients with acute myeloid leukemia (AML). Starting with a cohort of 29,915 potentially eligible patients with a diagnosis of AML, we were able to identify 211 patients treated with HCT and 774 treated with chemotherapy alone where we were sufficiently confident of the diagnosis and treatment path to allow analysis. Administrative claims data provide an avenue to meet the need for health care costs, resource utilization, and outcome information. However, when using these data, a balance between clinical knowledge and applied methods is critical to identifying a valid study cohort and accurate measures of costs and resource utilization., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Mobile imaging, such as viewing radiographs as text messages, is increasingly prevalent in clinical settings. The purpose of this study was to determine whether remote diagnosis of pediatric elbow fractures using smartphone technology is reliable. In addition, this study aimed to determine whether the assessment regarding the decision for operative treatment is affected by evaluation of images on a mobile device as opposed to standard picture archiving and communication system (PACS)., Methods: Standard anteroposterior and lateral radiographs of 50 pediatric elbow trauma cases were evaluated by 2 fellowship-trained pediatric orthopaedic surgeons and 2 senior orthopaedic residents. Raters were asked to classify the case as any of 6 diagnoses: supracondylar humerus, lateral condyle, medial epicondyle, radial neck fracture, positive posterior fat pad sign, or normal pediatric elbow. Raters were asked to choose operative or conservative treatment. After 1 week, photographs of the same images were taken from a standardized distance from a computer monitor with an iPhone 5 camera and transmitted by multimedia messaging to each rater. The same questions were again posed to raters. Interobserver and intraobserver reliabilities were calculated by Cohen κ-statistics with bootstrapped 95% confidence intervals., Results: Intraobserver reliability of classification of injuries on PACS compared with smartphone images was excellent, with an overall κ of 0.91. Treatment decision also demonstrated excellent intraobserver reliability (PACS vs. smartphones) with a κ of 0.86 for all raters., Conclusions: Diagnosis of pediatric elbow injuries can be made equally reliably based on either PACS or transmitted multimedia messaging images taken with an iPhone camera from a computer screen and viewed on a smartphone. Treatment decisions can also be made reliably based on either image modality., Clinical Relevance: Using smartphones to transmit and display radiographs, which is common in current clinical practice, is effective and reliable for diagnosis and treatment planning of pediatric elbow injuries.

Arabidopsis halleri is a model species for the study of plant adaptation to extreme metallic conditions. In this species, cadmium (Cd) tolerance seems to be constitutive, and the mechanisms underlying the trait are still poorly understood. A previous quantitative trait loci (QTL) analysis performed on A. halleri × Arabidopsis lyrata backcross population1 identified the metal-pump gene Heavy Metal ATPase4 as the major genetic determinant for Cd tolerance. However, although necessary, Heavy Metal ATPase4 alone is not sufficient for determining this trait. After fine mapping, a gene encoding a calcium(2+)/hydrogen(+) antiporter, cation/hydrogen(+) exchanger1 (CAX1), was identified as a candidate gene for the second QTL of Cd tolerance in A. halleri. Backcross population1 individuals displaying the A. halleri allele for the CAX1 locus exhibited significantly higher CAX1 expression levels compared with the ones with the A. lyrata allele, and a positive correlation between CAX1 expression and Cd tolerance was observed. Here, we show that this QTL is conditional and that it is only detectable at low external Ca concentration. CAX1 expression in both roots and shoots was higher in A. halleri than in the close Cd-sensitive relative species A. lyrata and Arabidopsis thaliana. Moreover, CAX1 loss of function in A. thaliana led to higher Cd sensitivity at low concentration of Ca, higher sensitivity to methylviologen, and stronger accumulation of reactive oxygen species after Cd treatment. Overall, this study identifies a unique genetic determinant of Cd tolerance in the metal hyperaccumulator A. halleri and offers a new twist for the function of CAX1 in plants., (© 2015 American Society of Plant Biologists. All Rights Reserved.)

Aim: Water in sink drains is a known source of gram-negative bacteria. We aimed to evaluate the impact of self-disinfecting sink drains on the emission of aerosolised bacteria and on Pseudomonas aeruginosa acquisition among neonates., Methods: Aerosol bacterial growth and patient Pseudomonas aeruginosa acquisition rates were measured at baseline (Phase One), for 13 months after sinks were relocated or redesigned during refurbishment (Phase Two) and for 13 months after introducing self-disinfecting sink drains (Phase Three)., Results: Cultures were positive for bacterial growth in 56%, 24% and 13% of the tested aerosols in Phases One, Two and Three, respectively. Comparing Phases Two and Three produced an odds ratio (OR) of 0.47, with a 95% confidence interval (CI) of 0.22-0.99 (p = 0.047), for all bacteria and an OR of 0.31 and CI of 0.12-0.79 (p = 0.013) for Pseudomonas aeruginosa. Rates of Pseudomonas aeruginosa positive clinical cultures were 0.34, 0.27 and 0.13 per 1000 patient days during the respective phases, with a significant increase of time to the next positive clinical culture in Phase Three., Conclusion: Self-disinfecting sink drains were superior to sink replacements in preventing emissions from aerosols pathogens and may reduce hospital-acquired infections. The bioburden reduction should be confirmed in a larger multicentre trial., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Certain molecular mechanisms of Cd tolerance and accumulation have been identified in the model species Arabidopsis halleri, while intraspecific variability of these traits and the mechanisms of shoot detoxification were little addressed. The Cd tolerance and accumulation of metallicolous and non-metallicolous A. halleri populations from different genetic units were tested in controlled conditions. In addition, changes in shoot cell wall composition were investigated using Fourier transform infrared spectroscopy. Indeed, recent works on A. halleri suggest Cd sequestration both inside cells and in the cell wall/apoplast. All A. halleri populations tested were hypertolerant to Cd, and the metallicolous populations were on average the most tolerant. Accumulation was highly variable between and within populations, and populations that were non-accumulators of Cd were identified. The effect of Cd on the cell wall composition was quite similar in the sensitive species A. lyrata and in A. halleri individuals; the pectin/polysaccharide content of cell walls seems to increase after Cd treatment. Nevertheless, the changes induced by Cd were more pronounced in the less tolerant individuals, leading to a correlation between the level of tolerance and the extent of modifications. This work demonstrated that Cd tolerance and accumulation are highly variable traits in A. halleri, suggesting adaptation at the local scale and involvement of various molecular mechanisms. While in non-metallicolous populations drastic modifications of the cell wall occur due to higher Cd toxicity and/or Cd immobilization in this compartment, the increased tolerance of metallicolous populations probably involves other mechanisms such as vacuolar sequestration., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Arabidopsis halleri is a model plant for Zn and Cd hyperaccumulation. The objective of this study was to determine the relationship between the chemical forms of Cd, its distribution in leaves, and Cd accumulation and tolerance. An interspecific cross was carried out between A. halleri and the non-tolerant and non-hyperaccumulating relative A. lyrata providing progenies segregating for Cd tolerance and accumulation. Cd speciation and distribution were investigated using X-ray absorption spectroscopy and microfocused X-ray fluorescence. In A. lyrata and non-tolerant progenies, Cd was coordinated by S atoms only or with a small contribution of O groups. Interestingly, the proportion of O ligands increased in A. halleri and tolerant progenies, and they were predominant in most of them, while S ligands were still present. Therefore, the binding of Cd with O ligands was associated with Cd tolerance. In A. halleri, Cd was mainly located in the xylem, phloem, and mesophyll tissue, suggesting a reallocation process for Cd within the plant. The distribution of the metal at the cell level was further discussed. In A. lyrata, the vascular bundles were also Cd enriched, but the epidermis was richer in Cd as compared with the mesophyll. Cd was identified in trichomes of both species. This work demonstrated that both Cd speciation and localization were related to the tolerance character of the plant., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Supracondylar humeral fractures are common in the pediatric population and can result in complications caused by both the injury itself and surgical or nonsurgical treatment. Neurologic complications are frequent, with the anterior interosseous nerve being the most common nerve affected. Vascular injuries, although less common, can result in long-term sequelae and should be recognized and treated promptly. Loss of reduction can occur with both surgical and nonsurgical treatment. Compartment syndrome and infection, although rare, require rapid recognition and treatment. It is important to be familiar with the potential complications surrounding the treatment of pediatric supracondylar humeral fractures to maximize outcomes and know when a referral may be warranted.