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Lene Sofie Granfeldt Østgård,1,2 Jan Maxwell Nørgaard,1 Klas Kræsten Raaschou-Jensen,3 Robert Schou Pedersen,4 Dorthe Rønnov-Jessen,5 Per Troellund Pedersen,6 Inge Høgh Dufva,7 Claus Werenberg Marcher,8 Ove Juul Nielsen,9 Marianne Tang Severinsen,10,11 Lone Smidstrup Friis9 1Department of Hematology, 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 3Department of Hematology, Copenhagen University Hospital, Roskilde, 4Department of Medicine, Holstebro Hospital, Holstebro, 5Department of Hematology, Vejle Hospital, Vejle, 6Department of Medicine, Esbjerg Hospital, Esbjerg, 7Department of Hematology, Copenhagen University Hospital, Herlev, 8Department of Hematology, Odense University Hospital, Odense, 9Department of Hematology, The National University Hospital, Rigshospitalet, Copenhagen, 10Department of Hematology, Aalborg University Hospital, Aalborg, Denmark, 11Department of Clinical Medicine, Aalborg University, Aalborg, Denmark Aim of database: The main aim of the Danish National Acute Leukemia Registry (DNLR) was to obtain information about the epidemiology of the hematologic cancers acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). Study population: The registry was established in January 2000 by the Danish Acute Leukemia Group and has been expanded over the years. It includes adult AML patients diagnosed in Denmark since 2000, ALL patients diagnosed since 2005, and MDS patients diagnosed since 2010. The coverage of leukemia patients exceeds 99%, and the coverage of MDS patients is currently 90%. Main variables and descriptive data: Approximately, 250 AML patients, 25 ALL patients, and 230 MDS patients are registered in the DNLR every year. In January 2015, the registry included detailed patient characteristics, disease characteristics, treatment characteristics, and outcome data on more than 3,500 AML, 300 ALL, and 1,100 MDS patients. Many of the included prognostic variables have been found to be of high quality including positive predictive values and completeness exceeding 90%. These variables have been used in prognostic observational studies in the last few years. To ensure this high coverage, completeness, and quality of data, linkage to the Danish Civil Registration System and the Danish National Registry of Patients, and several programmed data entry checks are used. Conclusion: The completeness and positive predictive values of the leukemia data have been found to be high. In recent years, the DNLR has shown to be an important high-quality resource for clinical prognostic research. Keywords: data quality, registries, population-based, acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome

Lene Sofie Granfeldt Østgård,1,2 Jan Maxwell Nørgaard,1 Marianne Tang Severinsen,3 Henrik Sengeløv,4 Lone Friis,5 Morten Krogh Jensen,6 Ove Juul Nielsen,7 Mette Nørgaard2 1Department of Hematology, 2Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Hematology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Hematology, Rigshospitalet, Copenhagen, Denmark; 5Department of Hematology, Odense University Hospital, Odense, Denmark; 6Department of Hematology, Herlev Hospital, Herlev, Denmark; 7Department of Hematology, Rigshospitalet, Copenhagen, Denmark Background: The Danish National Acute Leukemia Registry (DNLR) has documented coverage of above 98.5%. Less is known about the quality of the recorded data. Objective: To describe the present coverage of the DNLR, its completeness, and accuracy of individual variables for acute myeloid leukemia (AML). Furthermore, as a second measure of true coverage of the DNLR, to estimate AML incidence in Denmark from DNLR data and compare it to incidence reported from other AML registries. Patients and methods: By the end of December 2011, the DNLR (established January 2000) included detailed data on a large, well-defined, and nonselected Danish population of 2,665 AML patients. We estimated positive predictive values (PPVs) and completeness for 30 variables, which included patient and disease characteristics, treatment, and treatment outcomes. We identified 260 AML patients (10% of all AML patients recorded in the DNLR). We used information from medical records as the gold standard. Results: Using the Danish National Registry of Patients as a reference, the coverage of the DNLR was 99.6%. The PPVs of the individual variables ranged from 89.4% to 100%. The completeness of individual variables varied between 60.7% and 100%. Stratification by time of registration in the DNLR (before 2006 versus 2006 and later) revealed higher PPVs and lower frequencies of missing data from 2006. Sex-adjusted incidence rates were 6.2/100,000 person-years (95% confidence interval 5.8–6.6) in males and 4.9/100,000 person-years (95% confidence interval 4.5–5.4) in females. Yearly incidence rates of AML were higher than the incidence rates reported from Sweden (4.5 and 4.2/100,000) and the US (4.5 and 3.1/100,000 in Caucasians). Conclusion: With few exceptions, there were high values for PPVs and completeness of recorded data. Data accuracy and completeness have improved since the registry was established. The estimated incidence may indicate that the DNLR truly is more complete than other registries. In conclusion, the DNLR is a valuable resource for clinical research of AML. Keywords: acute myeloid leukemia, incidence, registration completeness, validation studies

Smog chamber experiments were conducted to establish the atmospheric chemistry of ( E )- and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 . Kinetics of the reactions of the two compounds with Cl atoms and OH radicals were measured using relative rate techniques, giving k (Cl + ( E )-CF 3 CF 2 CH═CHCF 2 CF 3 ) = (5.63 ± 0.84) × 10 -12 , k (Cl + ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 ) = (1.17 ± 0.20) × 10 -11 , k (OH + ( E )-CF 3 CF 2 CH═CHCF 2 CF 3 ) = (1.64 ± 0.21) × 10 -13 , and k (OH + ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 ) = (3.13 ± 0.38) × 10 -13 cm 3 molecule -1 s -1 in 680 Torr air/N 2 /O 2 diluents at 296 ± 2 K. Rate coefficients for the reactions with O 3 , k (O 3 + ( E )-CF 3 CF 2 CH═CHCF 2 CF 3 ) ∼ 1 × 10 -22 and k (O 3 + ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 ) ≤ 5× 10 -24 cm 3 molecule -1 s -1 , were established using absolute techniques in a 680 Torr air diluent and 296 ± 2 K. The Cl reaction with ( E )-CF 3 CF 2 CH═CHCF 2 CF 3 gives CF 3 CF 2 CHClC(O)CF 2 CF 3 as the sole oxidation product, whereas the reaction with ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 also gives rise to the formation of the ( E )-isomer in minor yields. The reaction of OH radicals with CF 3 CF 2 CH═CHCF 2 CF 3 gives CF 3 CF 2 CHO in a yield of 177 ± 17%. The main atmospheric fate of ( E ) - and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 is the reaction with OH radicals, resulting in overall atmospheric lifetime estimates of 71 and 37 days, for ( E )- and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 , respectively. The IR absorption cross sections are reported, and the global warming potentials of ( E )- and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 for the 20-, 100-, and 500-year time horizons are calculated to be 36, 10, and 3 for the ( E ) - isomer and 11, 3, and 1 for the ( Z )-isomer, respectively. Atmospheric processing of ( E )- and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 is expected to yield CF 3 CF 2 COOH and CF 3 COOH in yields of <10%. This study provides a comprehensive description of the atmospheric chemistry and fate of ( E )- and ( Z )-CF 3 CF 2 CH═CHCF 2 CF 3 .

All sectors of society must reduce their carbon footprint to mitigate climate change, and the healthcare community is no exception. This narrative review focuses on the environmental concerns associated with the emissions of volatile anaesthetic agents, some of which are potent greenhouse gases. This review provides an understanding of the global warming potential metric, as well as the concepts of atmospheric lifetime and radiative efficiency. The state of knowledge of the environmental impact and possible climate forcing of emitted volatile anaesthetic agents are reviewed. Additionally, the review discusses how climate metrics can guide mitigation strategies to reduce emissions and suggests present and future options for mitigating the climate impact., (© 2024 Association of Anaesthetists.)

There is increasing concern within the health-care community about the role care delivery plays in environmental degradation, sparking research into how to reduce pollution from clinical practice. Inhaled anaesthetics is a particular research area of interest for two reasons. First, several gases are potent greenhouse gases, and waste gas is mostly emitted directly to the environment. Second, there are options to reduce gas waste and substitute medications and procedures with fewer embodied emissions while delivering high-quality care. Performance improvements are contingent on a proper understanding of the emission estimates and climate metrics used to ensure consistent application in guiding mitigation strategies and accounting at various scales. We review the current literature on the environmental impact and the estimation of the potential climate forcing of common inhaled anaesthetic drugs: desflurane, sevoflurane, isoflurane, methoxyflurane, and nitrous oxide., Competing Interests: Declaration of interests MPSA reports receiving grants and support for attending meetings or travel from the National Science Foundation. JDS reports receiving grants from the Commonwealth Fund, Canadian Institutes of Health Research, and National Science Foundation; receiving consulting fees from the Institute for Healthcare Improvement; receiving lecture honorarium from the Medical Society Consortium on Climate Change and Health, Society for Technology in Anesthesiology, Peking University Institute for Global Health and Development Forum, Duke University Department of Anesthesiology, University of Toronto Institute of Health Policy, Management and Evaluation, and Agency for Healthcare Research and Quality; receiving lecture honorarium from and support for being a session moderator for the Society for Paediatric Anaesthesia in New Zealand and Australia/Australia New Zealand Paediatric Surgeons bi-annual meeting; and receiving lecture honorarium from and being a panellist for the International Forum on Perioperative Safety and Quality. JDS is also a panellist in the World Innovation Summit in Health annual meeting and serves as a Chair of the American Society of Anesthesiologists Committee on Environmental Health. OJN declares no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Potent inhaled anaesthetics are halogenated hydrocarbons with a large global warming effect. The use of fluorinated hydrocarbons (most are not anaesthetics) are being restricted but volatile anaesthetics have been exempted from legislation, until now: the EU has formulated a proposal to ban or at least severely restrict the use of desflurane starting January 2026. This narrative review addresses the implications of a politics-driven decision - without prior consultation with major stakeholders, such as the European Society of Anaesthesiology and Intensive Care (ESAIC) - on daily anaesthesia practice and reviews the potential scientific arguments that would support stopping the routine use of desflurane in anaesthetic practice. Of note, banning or severely restricting the use of one anaesthetic agent should not distract the user from sensible interventions like reducing fresh gas flows and developing technology to capture and recycle or destroy the wasted potent inhaled anaesthetics that we will continue to use. We call to join efforts to minimise our professional environmental footprint., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Smog chambers interfaced with in situ FT-IR detection were used to investigate the kinetics and mechanisms of the Cl atom, OH radical, and O 3 initiated oxidation of ( Z )- and ( E )-1,2-dichloroethene (CHClCHCl) under atmospheric conditions. Relative and absolute rate methods were used to measure k (Cl + ( Z )-CHClCHCl) = (8.80 ± 1.75) × 10 -11 , k (Cl + ( E )-CHClCHCl) = (8.51 ± 1.69) × 10 -11 , k (OH + ( Z )-CHClCHCl) = (2.02 ± 0.43) × 10 -12 , k (OH + ( E )-CHClCHCl) = (1.94 ± 0.43) × 10 -12 , k (O 3 + ( Z )-CHClCHCl) = (4.50 ± 0.45) × 10 -21 , and k (O 3 + ( E )-CHClCHCl) = (1.02 ± 0.10) × 10 -19 cm 3 molecule -1 s -1 in 700 Torr of N 2 /air diluent at 298 ± 2 K. Pressure dependencies for the Cl atom reaction kinetics were observed for both isomers, consistent with isomerization occurring via Cl atom elimination from the chemically activated CHCl-CHCl-Cl adduct. The observed products from Cl initiated oxidation were HC(O)Cl (117-133%), CHCl 2 CHO (29-30%), and the corresponding CHClCHCl isomer (11-20%). OH radical initiated oxidation gives HC(O)Cl as a major product. For reaction of OH with ( E )-CHClCHCl, ( Z )-CHClCHCl was also observed as a product. A significant chlorine atom elimination channel was observed experimentally (HCl yield) and supported by computational results. Photochemical ozone creation potentials of 12 and 11 were estimated for ( Z )- and ( E )-CHClCHCl, respectively. Finally, an empirical kinetic relationship is explored for the addition of OH radicals or Cl atoms to small alkenes. The results are discussed in the context of the atmospheric chemistry of ( Z )- and ( E )-CHClCHCl.

We investigated trends of survival in a population-based cohort study of all 181 adults who received HCT for ALL in Denmark between 2000-2019. Patients had a median (min-max) age of 36 (18-74) years at HCT and were followed for a median of eight years. Overall survival (OS) improved over time with an estimated 2-year OS of 49% (CI 27-66%) in year 2000 versus 77% (CI 59-88%) in year 2019. More patients achieved cure over time (OR for cure per year 1.07, CI 1.00-1.15), while the rate of death in non-cured patients remained stable (HR of excess mortality per year 0.99, CI 0.93-1.06). Relapse decreased over time (HR 0.92 per year, CI 0.87-0.98), whereas non-relapse mortality did not change notably (HR 0.98 per year, CI 0.93-1.04). In conclusion, survival after HCT in adults with ALL has improved over the past two decades, primarily due to more patients achieving cure.

Long path length FTIR-smog chamber techniques were used to study the title reactions in 700 Torr of N 2 , oxygen or air diluent at 296 ± 2 K. Values of k (Cl + CF 3 CN) = (2.43 ± 0.33) × 10 -15 and k (OH + CF 3 CN) = (4.61 ± 0.34) × 10 -15 cm 3 molecule -1 s -1 were measured. There was no discernible reaction of CF 3 CN with O 3 and an upper limit of k (O 3 + CF 3 CN) ≤ 7.9 × 10 -24 cm 3 molecule -1 s -1 was established. The IR spectra of CF 3 CN and CF 3 CF 2 CN are reported. The atmospheric lifetime of CF 3 CN is determined by the reaction with OH and is approximately 6.9 years. Reaction of CF 3 CN with Cl atoms in a chamber study gives ( Z -) and/or ( E -) CF 3 CClNCl and CF 3 C(O)Cl as major primary products. Under environmental conditions, the OH radical initiated oxidation gives COF 2 in a yield of (96 ± 8)%. The global warming potential for CF 3 CN is estimated as 1030 for a 100 year time horizon.

Fourier transform infrared spectroscopy has been used to follow the reaction of CH 3 OCF 2 CHF 2 with either Cl or OH radicals within a photoreactor. Rate constants of k (OH + CH 3 OCF 2 CHF 2 ) = (2.25 ± 0.60) × 10 -14 cm 3 molecule -1 s -1 and k (Cl + CH 3 OCF 2 CHF 2 ) = (2.50 ± 0.39) × 10 -13 cm 3 molecule -1 s -1 were determined at 296 ± 2 K. Theoretical and experimental investigation of the Cl + CH 3 OCF 2 CHF 2 reaction identified the formation of two main products, HC(O)OCF 2 CHF 2 and COF 2 . Chlorine (and OH) radicals react with CH 3 OCF 2 CHF 2 by H-abstraction from either the -CH 3 or -CHF 2 site. Abstraction from the -CH 3 site was determined to constitute at least 60%, as determined from the formation of the primary product, HC(O)OCF 2 CHF 2 , which can only form from this abstraction site. At longer reaction times, HC(O)OCF 2 CHF 2 further reacts and the yield of COF 2 approaches two, the maximum possible with the number of F atoms in the reactant. The atmospheric lifetime of CH 3 OCF 2 CHF 2 with OH radicals was determined to be 1.4 years. The global warming potentials over 20-, 100-, and 500-year time horizons were estimated to be 325, 88, and 25, respectively.

We argue that there is a need for a more precise of PFAS in a way that avoids including compounds with single CF 3 -, -CF 2 -, or CF- groups and excludes TFA and compounds that degrade to just give TFA. An example that meets this need is the definition by the U.S. Environmental Protection Agency of PFAS as "per- and polyfluorinated substances that structurally contain the unit R-(CF 2 )-C(F)(R 1 )R 2 . Both the CF 2 and CF moieties are saturated carbons and none of the R groups (R, R 1 , or R 2 ) can be hydrogen". Adoption of this definition, or one like it, would place future technical and regulatory discussions of the environmental impacts of organo-fluorine compounds on a sounder technical footing by focusing PFAS discussions and regulation on long-chain perfluoroalkyl sulfonic acids and perfluoroalkyl carboxylic acids.

We here reflect on two important articles on stratospheric ozone depletion written by P. J. Crutzen (1974) and P. J. Crutzen and D. H. Ehhalt (1977) in the early 1970s. These articles provide a clear description of the stratosphere and the most important chemical reactions involved in stratospheric ozone depletion. They present modeling results and provide recommendations for future research on stratospheric ozone depletion caused by chloro-fluoro-carbons, supersonic transport, nitrous oxide, and nuclear explosions. These two articles represent the beginning of a scientific era, which led to discovery of the Antarctic ozone hole and political action in the form of the Montreal Protocol and its amendments.

Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B ( n = 12) or posaconazole ( n = 1) given as monotherapy ( n = 4) or in combination with isavuconazole/posaconazole ( n = 3/6) and terbinafine ( n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy ( n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.

Background: The risk of venous thromboembolism is increased in adults and enhanced by asparaginase-based chemotherapy, and venous thromboembolism introduces a secondary risk of treatment delay and premature discontinuation of key anti-leukaemic agents, potentially compromising survival. Yet, the trade-off between benefits and harms of primary thromboprophylaxis in adults with acute lymphoblastic leukaemia (ALL) treated according to asparaginase-based regimens is uncertain.  OBJECTIVES: The primary objectives were to assess the benefits and harms of primary thromboprophylaxis for first-time symptomatic venous thromboembolism in adults with ALL receiving asparaginase-based therapy compared with placebo or no thromboprophylaxis. The secondary objectives were to compare the benefits and harms of different groups of primary systemic thromboprophylaxis by stratifying the main results per type of drug (heparins, vitamin K antagonists, synthetic pentasaccharides, parenteral direct thrombin inhibitors, direct oral anticoagulants, and blood-derived products for antithrombin substitution)., Search Methods: We conducted a comprehensive literature search on 02 June 2020, with no language restrictions, including (1) electronic searches of Pubmed/MEDLINE; Embase/Ovid; Scopus/Elsevier; Web of Science Core Collection/Clarivate Analytics; and Cochrane Central Register of Controlled Trials (CENTRAL) and (2) handsearches of (i) reference lists of identified studies and related reviews; (ii) clinical trials registries (ClinicalTrials.gov registry; the International Standard Randomized Controlled Trial Number (ISRCTN) registry; the World Health Organisation's International Clinical Trials Registry Platform (ICTRP); and pharmaceutical manufacturers of asparaginase including Servier, Takeda, Jazz Pharmaceuticals, Ohara Pharmaceuticals, and Kyowa Pharmaceuticals), and (iii) conference proceedings (from the annual meetings of the American Society of Hematology (ASH); the European Haematology Association (EHA); the American Society of Clinical Oncology (ASCO); and the International Society on Thrombosis and Haemostasis (ISTH)). We conducted all searches from 1970 (the time of introduction of asparaginase in ALL treatment). We contacted the authors of relevant studies to identify any unpublished material, missing data, or information regarding ongoing studies., Selection Criteria: Randomised controlled trials (RCTs); including quasi-randomised, controlled clinical, cross-over, and cluster-randomised trial designs) comparing any parenteral/oral preemptive anticoagulant or mechanical intervention with placebo or no thromboprophylaxis, or comparing two different pre-emptive anticoagulant interventions in adults aged at least 18 years with ALL treated according to asparaginase-based chemotherapy regimens. For the description of harms, non-randomised observational studies with a control group were eligible for inclusion.  DATA COLLECTION AND ANALYSIS: Using a standardised data collection form, two review authors independently screened and selected studies, extracted data, assessed risk of bias for each outcome using standardised tools (RoB 2.0 tool for RCTs and ROBINS-I tool for non-randomised studies) and the certainty of evidence for each outcome using the GRADE approach. Primary outcomes included first-time symptomatic venous thromboembolism, all-cause mortality, and major bleeding. Secondary outcomes included asymptomatic venous thromboembolism, venous thromboembolism-related mortality, adverse events (i.e. clinically relevant non-major bleeding and heparin-induced thrombocytopenia for trials using heparins), and quality of life. Analyses were performed according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. For non-randomised studies, we evaluated all studies (including studies judged to be at critical risk of bias in at least one of the ROBINS-I domains) in a sensitivity analysis exploring confounding.  MAIN RESULTS: We identified 23 non-randomised studies that met the inclusion criteria of this review, of which 10 studies provided no outcome data for adults with ALL. We included the remaining 13 studies in the 'Risk of bias' assessment, in which we identified invalid control group definition in two studies and judged outcomes of nine studies to be at critical risk of bias in at least one of the ROBINS-I domains and outcomes of two studies at serious risk of bias. We did not assess the benefits of thromboprophylaxis, as no RCTs were included. In the main descriptive analysis of harms, we included two retrospective non-randomised studies with outcomes judged to be at serious risk of bias. One study evaluated antithrombin concentrates compared to no antithrombin concentrates. We are uncertain whether antithrombin concentrates have an effect on all-cause mortality (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.26 to 1.19 (intention-to-treat analysis); one study, 40 participants; very low certainty of evidence). We are uncertain whether antithrombin concentrates have an effect on venous thromboembolism-related mortality (RR 0.10, 95% CI 0.01 to 1.94 (intention-to-treat analysis); one study, 40 participants; very low certainty of evidence). We do not know whether antithrombin concentrates have an effect on major bleeding, clinically relevant non-major bleeding, and quality of life in adults with ALL treated with asparaginase-based chemotherapy, as data were insufficient. The remaining study (224 participants) evaluated prophylaxis with low-molecular-weight heparin versus no prophylaxis. However, this study reported insufficient data regarding harms including all-cause mortality, major bleeding, venous thromboembolism-related mortality, clinically relevant non-major bleeding, heparin-induced thrombocytopenia, and quality of life. In the sensitivity analysis of harms, exploring the effect of confounding, we also included nine non-randomised studies with outcomes judged to be at critical risk of bias primarily due to uncontrolled confounding. Three studies (179 participants) evaluated the effect of antithrombin concentrates and six studies (1224 participants) evaluated the effect of prophylaxis with different types of heparins. When analysing all-cause mortality; venous thromboembolism-related mortality; and major bleeding (studies of heparin only) including all studies with extractable outcomes for each comparison (antithrombin and low-molecular-weight heparin), we observed small study sizes; few events; wide CIs crossing the line of no effect; and substantial heterogeneity by visual inspection of the forest plots. Although the observed heterogeneity could arise through the inclusion of a small number of studies with differences in participants; interventions; and outcome assessments, the likelihood that bias due to uncontrolled confounding was the cause of heterogeneity is inevitable. Subgroup analyses were not possible due to insufficient data.  AUTHORS' CONCLUSIONS: We do not know from the currently available evidence, if thromboprophylaxis used for adults with ALL treated according to asparaginase-based regimens is associated with clinically appreciable benefits and acceptable harms. The existing research on this question is solely of non-randomised design, seriously to critically confounded, and underpowered with substantial imprecision. Any estimates of effect based on the existing insufficient evidence is very uncertain and is likely to change with future research., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

An investigation of CCl3COCl was conducted with the purpose of using the compound as an alternative Cl atom precursor in laboratory settings. CCl3COCl can be used with or without O2 as a source of Cl atoms and photolysis studies in air and N2 diluent displayed COCl2 and CO as being the major photolysis products. Relative rate studies were performed to determine the Cl atom rate coefficients for reaction with CH3Cl and C2H2 and the results were in agreement with literature values. Cl atom rate coefficients for reaction with n-CH2[double bond, length as m-dash]CH(CH2)3CN and n-CH2[double bond, length as m-dash]CH(CH2)4CN were determined as (2.95 ± 0.58) × 10-10 and (3.73 ± 0.60) × 10-10 cm3 molecule-1 s-1, respectively. CCl3COCl requires UV-C irradiation, so not all molecules are feasible for use in e.g. relative rate studies. Furthermore, it is recommended to perform experiments with O2 present, as this minimizes IR feature disturbance from product formation.

We have characterized the various pathways for OH radical (OH˙) induced decomposition of tert-butyl methyl ether (MTBE) and found an oxidative pathway that leads to complete degradation under the prerequisite that OH radicals are present in excess. A simple polarizable continuum model is used to predict the behavior in an aqueous medium and the behavior is unchanged compared to that in the gas phase. The computational study has also revealed some of the fundamental aspects of hydrogen transfer from asymmetric ethers; the ˙OH assisted hydrogen abstraction has a barrier when the reaction takes place at a distance from the heteroatom, that is, at the tert-butyl group, whereas hydrogen abstraction from the methyl group proceeds without a barrier. The addition of ˙OH to (CH3)3COCH2˙ also proceeds without a barrier, and so does hydrogen abstraction from the resulting adduct ((CH3)3COCH2OH) to form (CH3)3COCH(OH)˙. However, a barrier is yet again found in the hydrogen abstraction from the latter to form (CH3)3COCH[double bond, length as m-dash]O and yet again in the formation of the formyl radical (CH3)3COC[double bond, length as m-dash]O˙ by hydrogen abstraction. The latter is the last step before the final stage of complete oxidation of MTBE to form CO2.

Smog chamber/FTIR techniques were used to investigate the kinetics and mechanism of the Cl atom and OH radical initiated oxidation of 2,2-dichloroethanol at (296 ± 1) K. Relative rate methods were used to measure k(Cl + CHCl 2 CH 2 OH) = (5.87 ± 0.96) × 10 -12 and k(OH + CHCl 2 CH 2 OH) = (5.54 ± 1.94) × 10 -13 cm 3 molecule -1 s -1 . Chlorine atom initiated oxidation of CHCl 2 CH 2 OH in one atmosphere of air gives HCOCl, CHCl 2 CHO, and COCl 2 in yields of (62 ± 5)%, (39 ± 10)%, and (8 ± 2)%, respectively. The rate constant k(Cl + CHCl 2 CHO) = (8.3 ± 16) × 10 -12 cm 3 molecule -1 s -1 was determined and the IR spectra of CHCl 2 CHO is reported for the first time. The atmospheric lifetime for CHCl 2 CH 2 OH is estimated as 21 days. The experimental results are discussed in the context of the atmospheric chemistry of chlorinated alcohols.

Purpose: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored., Patients and Methods: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol., Results: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse., Conclusion: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.

Fourier transform infrared smog chamber techniques were used to study the kinetics and mechanisms of the reactions of Cl atoms and OH radicals with pentafluorophenol (C 6 F 5 OH) in 700 Torr total pressure of air or N 2 diluent at 296 ± 2 K. Rate constants k (OH + C 6 F 5 OH) = (6.88 ± 1.37) × 10 -12 cm 3 molecule -1 s -1 and k (Cl + C 6 F 5 OH) = (2.52 ± 0.31) × 10 -11 cm 3 s -1 molecule -1 in 700 Torr air diluent were determined. In 700 Torr N 2 , the rate constant for the reaction of C 6 F 5 OH with Cl atoms is linearly dependent on the Cl atom concentration. Product studies on this reaction in both 700 Torr air and 700 Torr N 2 diluent show the formation of nonconjugated products. The photolysis constant of C 6 F 5 OH was determined by 254 nm UV irradiation of a C 6 F 5 OH and CH 3 CHO mixture in 700 Torr air or N 2 at 296 ± 2 K and yielded a photolysis rate constant of J (C 6 F 5 OH) = (2.83 ± 0.25) × 10 -3 s -1 . Results are discussed with respect to the atmospheric chemistry of other halogenated aromatic species.

Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population., Objectives and Methods: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014., Results: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables., Conclusions: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)