Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study

Background Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as ‘accidents,’ and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. Methods Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention’s (CDC’s) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC’s Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. Results 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to$1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%—from $318.6 billion to$502.7 billion. National per capita costs of SIM doubled from $1,638 to$3,413 over the observation period; costs of the suicide component rose from $1,137 to$1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and − 1%, respectively. Conclusion The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs—fiscal, social, and personal—incurred by deaths due to self-injurious behaviors

Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Pathogens 5 (2009): e1000261, doi:10.1371/journal.ppat.1000261.Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.This research was supported by National Institutes of Health (NIH) grants R21 AI064118 (DEA) and R21 AI52792 (ST). HGM was supported in part by NIH contracts HHSN266200400041C and HHSN2662004037C (Bioinformatics Resource Centers) and by the G. Unger Vetlesen Foundation

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

PHASE 1 OF THE SMOKE AND EMISSIONS MODEL INTERCOMPARISON PROJECT (SEMIP): CREATION OF SEMIP AND EVALUATION OF CURRENT MODELS

Managers, regulators, and others often need information on the emissions from wildland fire and their expected smoke impacts. In order to create this information, combinations of models are utilized. The modeling steps follow a logical progression from fire activity through to emissions and dispersion. In general, several models and/or datasets are available for each modeling step, resulting in a large number of combinations that can be created to produce fire emissions or smoke impacts. Researchers, managers, and policy makers need information on how different model choices affect the resulting output, and guidance on what choices to make in selecting the models that best represent their management requirements. Baseline comparisons are needed between available models that highlight how they intercompare and, where possible, how their results compare with observations. As new models and methods are developed, standard protocols and comparison metrics are necessary to allow for these new systems to be understood in light of previous models and methods. The Smoke and Emissions Model Intercomparison Project (SEMIP) was designed to facilitate such comparisons. This project was designed to be the first step in a broader effort, and hence was titled Phase 1 of SEMIP. In Phase 1, SEMIP: • Examined the needs for fire emissions and smoke impact modeling; • Determined what data were available to help evaluate such models; • Identified a number of test cases that can serve as baseline comparisons between existing models and standard comparisons for new models; • Created a data warehouse and data sharing structure to help facilitate future comparisons; and • Performed a number of intercomparison analyses to examine existing models. SEMIP so far has resulted in: • Multiple peer reviewed journal articles and other documents; • Over 20 presentations; • Discussions with the EPA, JFSP, USFS F&AM, DOI, NWCG, and others on how to improve fire emissions calculations; • New fire emissions analysis tools; • Presentations and discussions with the JFSP on how to gather field observations useful to this type of analyses; and • Discussions with the JFSP on data sharing and archiving. SEMIP has also been acknowledged in recent RFAs from both the JFSP and NASA

Identification of Necessary Conditions for Arctic Transport of Smoke from United States Fires

The deposition of black carbon (BC), a dark absorbing aerosol, is a significant contributor to observed warming trends in the Arctic (Hansen and Nazarenko, 2004; Jacobson et al., 2007). Biomass burning outside of the Arctic, including wildland prescribed fires, is a major potential source of Arctic BC. Therefore, limiting or eliminating spring prescribed burning has been suggested to Congress as a BC reduction technique (e.g., Zender, 2007). However, there are large uncertainties in the current estimates of the sources, source regions, and transport and transformation pathways of BC transported to the Arctic region (Shindell et al., 2008; Hegg et al., 2009, Quinn et al., 2008). This study is the first comprehensive examination of the meteorological conditions required for emissions from the contiguous United States (CONUS) to be transported to Arctic. Using a simple trajectory modeling technique, we characterize the potential for transport of emissions from fires in CONUS to reach the Arctic and Greenland. The potential for Arctic transport is examined as • A 30-year climatology (1980-2009) of transport potential based on trajectory modeling using historical meteorology and split out by season, month, starting plume injection height, and time to reach the Arctic. • A real-time (daily) forecast system of transport potential to the Arctic that shows which layers of the atmosphere can reach the Arctic today, tomorrow, and the next day. The methods used here do not include wet or dry deposition and other factors that can further limit the ability of actual emissions to reach and deposit in the Arctic. Instead, by focusing on only one necessary aspect (a necessary but not sufficient condition) – the ability of the atmosphere to transport emissions – this study examines • Under what meteorological transport conditions can CONUS emissions potentially impact the Arctic? However, this allows for the ability to answer the corollary question: • Under what meteorological transport conditions will CONUS emissions not impact the Arctic? This inverse question allows for identification of times, locations, and plume injection heights where emissions sources (such as a prescribed burn) will not have an impact on the Arctic. This knowledge allows for both more targeted future studies and more precise mitigation strategies that do not focus on areas and times where Arctic impact is unlikely