Economic implications of FDA platelet bacterial guidance compliance options: Comparison of single-step strategies.

BACKGROUND: Bloodborne pathogens pose a major safety risk in transfusion medicine. To mitigate the risk of bacterial contamination in platelet units, FDA issues updated guidance materials on various bacterial risk control strategies (BRCS). This analysis presents results of a budget impact model updated to include 5- and 7-day pathogen reduced (PR) and large volumed delayed sampling (LVDS) BRCS. STUDY DESIGN AND METHODS: Model base-case parameter inputs were based on scientific literature, a survey distributed to 27 US hospitals, and transfusion experts' opinion. The outputs include hospital budget and shelf-life impacts for 5- and 7-day LVDS, and 5- and 7-day PR units under three different scenarios: (1) 100% LVDS, (2) 100% PR, and (3) mix of 50% LVDS - and 50% PR. RESULTS: Total annual costs from the hospital perspective were highest for 100% LVDS platelets (US$2.325M) and lowest for 100% PR-7 units (US$2.170M). Net budget impact after offsetting annual costs by outpatient reimbursements was 5.5% lower for 5-day PR platelets as compared to 5-day LVDS (US$1.663 vs. US$1.760M). A mix of 7-day LVDS and 5-day PR platelets had net annual costs that were 1.3% lower than for 100% 7-day LVDS, but 1.3% higher than for 100% 5-day PR. 7-day PR platelets had the longest shelf life (4.63 days), while 5-day LVDS had the shortest (2.00 days). DISCUSSION: The model identifies opportunities to minimize transfusion center costs for 5- and 7-day platelets. Budget impact models such as this are important for understanding the financial implications of evolving FDA guidance and new platelet technologies.

UVB (290-315 nm) inactivation of the SARS CoV-2 virus as a function of the standard UV index.

The inactivation time for the SARS CoV-2 virus, mostly by a portion of UVB spectrum (290-315 nm) in sunlight, has been estimated using radiative transfer calculations and a relative wavelength sensitivity virus inactivation action spectrum ALS. The action spectrum is adjusted for the SARS CoV-2 virus using a derived UV dose D90 = 3.2 J/m2 for 90% inactivation to match laboratory results for the inactivation of SARS CoV-2 virus droplets on steel mesh. Estimation of the time for 90% inactivation T90 at a specific geographic location can be simplified using the commonly published or calculated UV index (UVI). The use of UVI has the advantage that information on the amount of ozone, the site altitude, and the degree of cloud cover are built into the published UVI calculation. Simple power-law T90(UVI) = a UVI b fitting equations are derived that provide estimates of T90(UVI) for 270 specific locations. Using the results from the 270 locations, a generalized latitude θ dependence is presented for the coefficients a(θ) and b(θ) that enables T90(θ, UVI) to be estimated for 60°S ≤ θ ≤ 60°N and for noon and 2 h around local solar noon. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11869-021-01099-3.

Economic Analyses of Pathogen-Reduction Technologies in Blood Transfusion: A Systematic Literature Review.

BACKGROUND: Technologies used in the processing of whole blood and blood component products, including pathogen reduction, are continuously being adopted into blood transfusion workflows to improve process efficiencies. However, the economic implications of these technologies are not well understood. With the advent of these new technologies and regulatory guidance on bacterial risk-control strategies, an updated systematic literature review on this topic was warranted. OBJECTIVE: The objective of this systematic literature review was to summarize the current literature on the economic analyses of pathogen-reduction technologies (PRTs). METHODS: A systematic literature review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify newly published articles in PubMed, MEDLINE Complete, and EconLit from 1 January 2000 to 17 July 2019 related to economic evaluations of PRTs. Only full-text studies in humans published in English were included in the review. Both budget-impact and cost-effectiveness studies were included; common outcomes included cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: The initial searches identified 433 original abstracts, of which 16 articles were included in the final data extraction and reporting. Seven articles presented cost-effectiveness analyses and nine assessed budget impact. The introduction of PRT increased overall costs, and ICER values ranged widely across cost-effectiveness studies, from below $US150,000/QALY to upwards of $US20,000,000/QALY. This wide range of results was due to a multitude of factors, including comparator selection, target patient population, and scenario analyses included. CONCLUSIONS: Overall, the results of economic evaluations of bacterial risk-control strategies, regardless of mechanism, were highly dependent on the current screening protocols in place. The optimization of blood transfusion safety may not result in decisions made at the willingness-to-pay thresholds commonly seen in pharmaceutical evaluations. Given the critical public health role of blood products, and the potential safety benefits introduced by advancements, it is important to continue building this body of evidence with more transparency and data source heterogeneity. This updated literature review provides global context when making local decisions for the coverage of new and emerging bacterial risk-control strategies.

Comprehensive evaluations of diurnal NO2 measurements during DISCOVER-AQ 2011: effects of resolution-dependent representation of NO x emissions.

Nitrogen oxides (NO x =NO+NO2) play a crucial role in the formation of ozone and secondary inorganic and organic aerosols, thus affecting human health, global radiation budget, and climate. The diurnal and spatial variations in NO2 are functions of emissions, advection, deposition, vertical mixing, and chemistry. Their observations, therefore, provide useful constraints in our understanding of these factors. We employ a Regional chEmical and trAnsport model (REAM) to analyze the observed temporal (diurnal cycles) and spatial distributions of NO2 concentrations and tropospheric vertical column densities (TVCDs) using aircraft in situ measurements and surface EPA Air Quality System (AQS) observations as well as the measurements of TVCDs by satellite instruments (OMI: the Ozone Monitoring Instrument; GOME-2A: Global Ozone Monitoring Experiment - 2A), ground-based Pandora, and the Airborne Compact Atmospheric Mapper (ACAM) instrument in July 2011 during the DISCOVER-AQ campaign over the Baltimore-Washington region. The model simulations at 36 and 4 km resolutions are in reasonably good agreement with the regional mean temporospatial NO2 observations in the daytime. However, we find significant overestimations (underestimations) of model-simulated NO2 (O3) surface concentrations during night-time, which can be mitigated by enhancing nocturnal vertical mixing in the model. Another discrepancy is that Pandora-measured NO2 TVCDs show much less variation in the late afternoon than simulated in the model. The higher-resolution 4 km simulations tend to show larger biases compared to the observations due largely to the larger spatial variations in NO x emissions in the model when the model spatial resolution is increased from 36 to 4 km. OMI, GOME-2A, and the high-resolution aircraft ACAM observations show a more dispersed distribution of NO2 vertical column densities (VCDs) and lower VCDs in urban regions than corresponding 36 and 4 km model simulations, likely reflecting the spatial distribution bias of NO x emissions in the National Emissions Inventory (NEI) 2011.

Inactivation times from 290 to 315 nm UVB in sunlight for SARS coronaviruses CoV and CoV-2 using OMI satellite data for the sunlit Earth.

UVB in sunlight, 290-315 nm, can inactivate SARS CoV and SARS CoV-2 viruses on surfaces and in the air. Laboratory exposure to ultraviolet irradiance in the UVC range inactivates many viruses and bacteria in times less than 30 min. Estimated UVB inactivation doses from sunlight in J/m2 are obtained from UVC measurements and radiative transfer calculations, weighted by a virus inactivation action spectrum, using OMI satellite atmospheric data for ozone, clouds, and aerosols. For SARS CoV, using an assumed UVC dose near the mid-range of measured values, D 90 = 40 J/m2, 90% inactivation times T 90 are estimated for exposure to midday 10:00-14:00 direct plus diffuse sunlight and for nearby locations in the shade (diffuse UVB only). For the assumed D 90 = 40 J/m2 model applicable to SARS CoV viruses, calculated estimates show that near noon 11:00-13:00 clear-sky direct sunlight gives values of T 90 < 90 min for mid-latitude sites between March and September and less than 60 min for many equatorial sites for 12 months of the year. Recent direct measurements of UVB sunlight inactivation of the SARS CoV-2 virus that causes COVID-19 show shorter T 90 inactivation times less than 10 min depending on latitude, season, and hour. The equivalent UVC 254 nm D 90 dose for SARS CoV-2 is estimated as 3.2 ± 0.7 J/m2 for viruses on a steel mesh surface and 6.5 ± 1.4 J/m2 for viruses in a growth medium. For SARS CoV-2 clear-sky T 90 on a surface ranges from 4 min in the equatorial zone to less than 30 min in a geographic area forming a near circle with solar zenith angle < 60O centered on the subsolar point for local solar times from 09:00 to 15:00 h.

Assessment of NO2 observations during DISCOVER-AQ and KORUS-AQ field campaigns.

NASA's Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ, conducted in 2011-2014) campaign in the United States and the joint NASA and National Institute of Environmental Research (NIER) Korea-United States Air Quality Study (KORUS-AQ, conducted in 2016) in South Korea were two field study programs that provided comprehensive, integrated datasets of airborne and surface observations of atmospheric constituents, including nitrogen dioxide (NO2), with the goal of improving the interpretation of spaceborne remote sensing data. Various types of NO2 measurements were made, including in situ concentrations and column amounts of NO2 using ground- and aircraft-based instruments, while NO2 column amounts were being derived from the Ozone Monitoring Instrument (OMI) on the Aura satellite. This study takes advantage of these unique datasets by first evaluating in situ data taken from two different instruments on the same aircraft platform, comparing coincidently sampled profile-integrated columns from aircraft spirals with remotely sensed column observations from ground-based Pandora spectrometers, intercomparing column observations from the ground (Pandora), aircraft (in situ vertical spirals), and space (OMI), and evaluating NO2 simulations from coarse Global Modeling Initiative (GMI) and high-resolution regional models. We then use these data to interpret observed discrepancies due to differences in sampling and deficiencies in the data reduction process. Finally, we assess satellite retrieval sensitivity to observed and modeled a priori NO2 profiles. Contemporaneous measurements from two aircraft instruments that likely sample similar air masses generally agree very well but are also found to differ in integrated columns by up to 31.9 %. These show even larger differences with Pandora, reaching up to 53.9 %, potentially due to a combination of strong gradients in NO2 fields that could be missed by aircraft spirals and errors in the Pandora retrievals. OMI NO2 values are about a factor of 2 lower in these highly polluted environments due in part to inaccurate retrieval assumptions (e.g., a priori profiles) but mostly to OMI's large footprint (> 312 km2).

Regional characteristics of NO2 column densities from Pandora observations during the MAPS-Seoul campaign.

Vertical column density (VCD) of nitrogen dioxide (NO2) was measured using Pandora spectrometers at six sites on the Korean Peninsula during the Megacity Air Pollution Studies-Seoul (MAPS-Seoul) campaign from May to June 2015. To estimate the tropospheric NO2 VCD, the stratospheric NO2 VCD from the Ozone Monitoring Instrument (OMI) was subtracted from the total NO2 VCD from Pandora. European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis wind data was used to analyze variations in tropospheric NO2 VCD caused by wind patterns at each site. The Yonsei/SEO site was found to have the largest tropospheric NO2 VCD (1.49 DU on average) from a statistical analysis of hourly tropospheric NO2 VCD measurements. At rural sites, remarkably low NO2 VCDs were observed. However, a wind field analysis showed that trans-boundary transport and emissions from domestic sources lead to an increase in tropospheric NO2 VCD at NIER/BYI and KMA/AMY, respectively. At urban sites, high NO2 VCD values were observed under conditions of low wind speed, which were influenced by local urban emissions. Tropospheric NO2 VCD at HUFS/Yongin increases under conditions of significant transport from urban area of Seoul according to a correlation analysis that considers the transport time lag. Significant diurnal variations were found at urban sites during the MAPS-Seoul campaign, but not at rural sites, indicating that it is associated with diurnal patterns of NO2 emissions from dense traffic.

Comparison of Near-surface NO2 Pollution with Pandora Total Column NO2 during the Korea-United States Ocean Color (KORUS OC) Campaign.

Near-surface air quality (AQ) observations over coastal waters are scarce, a situation that limits our capacity to monitor pollution events at land-water interfaces. Satellite measurements of total column (TC) nitrogen dioxide (NO2) observations are a useful proxy for combustion sources but the once daily snapshots available from most sensors are insufficient for tracking the diurnal evolution and transport of pollution. Ground-based remote sensors like the Pandora Spectrometer Instrument (PSI) that have been developed to verify space-based total column NO2 and other trace gases are being tested for routine use as certified AQ monitors. The KORUS-OC (Korea-United States Ocean Color) cruise aboard the R/V Onnuri in May-June 2016 represented an opportunity to study AQ near the South Korean coast, a region affected by both local/regional and long-distance pollution sources. Using PSI data in direct-sun mode and in situ sensors for shipboard ozone, CO and NO2, we explore, for the first time, relationships between TC NO2 and surface AQ in this coastal region. Three case studies illustrate the value of the PSI as well as complexities in the surface-column NO2 relationship caused by varying meteorological conditions. Case Study 1 (25-26 May 2016) exhibited a high correlation of surface NO2 to TC NO2 measured by both PSI and Aura's Ozone Monitoring Instrument (OMI) but two other cases displayed poor relationships between in situ and TC NO2 due to decoupling of pollution layers from the surface. With suitable interpretation the PSI TC NO2 measurement demonstrates good potential for working with upcoming geostationary satellites to advance diurnal tracking of pollution.

Earth Observations from DSCOVR/EPIC Instrument.

The NOAA Deep Space Climate Observatory (DSCOVR) spacecraft was launched on February 11, 2015, and in June 2015 achieved its orbit at the first Lagrange point or L1, 1.5 million km from Earth towards the Sun. There are two NASA Earth observing instruments onboard: the Earth Polychromatic Imaging Camera (EPIC) and the National Institute of Standards and Technology Advanced Radiometer (NISTAR). The purpose of this paper is to describe various capabilities of the DSCOVR/EPIC instrument. EPIC views the entire sunlit Earth from sunrise to sunset at the backscattering direction (scattering angles between 168.5° and 175.5°) with 10 narrowband filters: 317, 325, 340, 388, 443, 552, 680, 688, 764 and 779 nm. We discuss a number of pre-processingsteps necessary for EPIC calibration including the geolocation algorithm and the radiometric calibration for each wavelength channel in terms of EPIC counts/second for conversion to reflectance units. The principal EPIC products are total ozone O3amount, scene reflectivity, erythemal irradiance, UV aerosol properties, sulfur dioxide SO2 for volcanic eruptions, surface spectral reflectance, vegetation properties, and cloud products including cloud height. Finally, we describe the observation of horizontally oriented ice crystals in clouds and the unexpected use of the O2 B-band absorption for vegetation properties.

Method-specific and unexplained reactivity in automated solid-phase testing and their association with specific antibodies.

CONCLUSIONS: The inherent tradeoff between sensitivity and specificity in the detection of unexplained antibodies has been the objective of many studies, editorials, and journal articles. Many publications note that no method is capable of detecting all clinically significant antibodies while avoiding all clinically insignificant antibodies. This study describes the frequency of nonspecific reactivity and unexplained reactivity in solid-phase testing, along with the subsequent development of specific antibodies (Abs). In this study, nonspecific reactivity (NS) is defined as method-specific panreactivity detected by solid-phase testing only, with no reactivity in other methods. Unexplained reactivity (UR) is defined as reactivity present and detectable in all test methods after all clinically significant antibodies were ruled out following a standard antibody identification algorithm using selected cell panels. This retrospective study evaluated antibody detection tests of patients at a single center for 2 years using two automated solid-phase instruments that used the same three-cell antibody detection test. Antibody identification was performed with solid-phase panels supplemented with a polyethylene glycol tube method as needed. Of the 1934 (5%) samples with a positive antibody detection test, 29 had unavailable work-up data, leaving 1905 (98.5%) samples eligible for inclusion in the study. The data revealed the following: Ab only 999 (52.4%); UR only 429 (22.5%); Ab and UR 227 (11.9%); NS only 206 (10.8%); Ab and NS 24 (1.3%); UR and NS 14 (0.7%); and Ab, UR, and NS 6 (0.3%). Patients with a positive follow-up antibody detection test had UR and NS replaced with a specific Ab in 23 of 656 UR (3%) and 8 of 230 NS (3%) cases, respectively. Additionally, six patients with UR developed a specific Ab along with persistent UR, and no patients with persistent NS developed a specific Ab. The study concluded that both UR and NS can be encountered in solid-phase testing, and both UR and NS can persist in follow-up testing. Specific Ab was observed to replace UR in a few patients.

Intraoperative Diagnosis and Management of Acute Hypotensive Blood Transfusion Reaction (AHTR): A Report of Two Cases.

BACKGROUND Acute hypotensive transfusion reaction (AHTR) is characterized by the abrupt onset of hypotension immediately after the start of transfusion and usually resolves when transfusion ceases. Recent studies have shown an association with pre-operative treatment with an angiotensin-converting enzyme (ACE) inhibitor. This report presents two cases of AHTR in non-related patients and describes the diagnosis and management. CASE REPORT A 68-year-old woman underwent lumbar fusion surgery due to spinal stenosis and an 86-year-old man underwent a pancreaticoduodenectomy (Whipple's procedure). Both patients had been treated pre-operatively with ACE inhibitors for hypertension. During surgery, both patients experienced acute profound intraoperative hypotension immediately after transfusion of packed red blood cells (RBCs). The blood transfusion was stopped immediately, and hemodynamic support was given with epinephrine, ephedrine, and phenylephrine. A diagnosis of acute hemolytic transfusion reaction was excluded by the direct antiglobulin test, serum hemolysis testing, exclusion of blood group mismatching, and a post-transfusion antibody screen. Other causes of hypotension were excluded. The two patients were confirmed t have had an AHTR, based on the current Centers for Disease Control and Prevention (CDC) criteria. In both cases, discontinuation of surgery was not possible, and surgery continued with intermittent hemodynamic support provided with catecholamines and vasopressin. CONCLUSIONS AHTR is a diagnosis of exclusion, based on laboratory and clinical findings. Antibody-mediated acute hemolytic transfusion reaction and any other causes of hypotension should be excluded as rapidly as possible. Patients who are at high risk of intraoperative bleeding might benefit from cessation of ACE inhibitors pre-operatively.

Bacterial contamination of platelets for transfusion: strategies for prevention.

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are rare but may be clinically devastating, while platelet storage conditions can support bacterial growth. Donor selection, blood diversion, and hemovigilance are effective but have limitations. Biofilm-producing species can adhere to biological and non-biological surfaces and evade detection. Primary bacterial culture testing of apheresis platelets is in routine use in the US. Pathogen reduction/inactivation technologies compatible with platelets use ultraviolet light-based mechanisms to target nucleic acids of contaminating bacteria and other pathogens. These methods have demonstrated safety and efficacy and represent a proactive approach for inactivating contaminants before transfusion to prevent transfusion-transmitted infections. One system, which combines ultraviolet A and amotosalen for broad-spectrum pathogen inactivation, is approved in both the US and Europe. Current US Food and Drug Administration recommendations advocate enhanced bacterial testing or pathogen reduction/inactivation strategies (or both) to further improve platelet safety. Risks of bacterial contamination of platelets and transfusion-transmitted infections have been significantly mitigated, but not eliminated, by improvements in prevention and detection strategies. Regulatory-approved technologies for pathogen reduction/inactivation have further enhanced the safety of platelet transfusions. Ongoing development of these technologies holds great promise.

Economic Implications of Pathogen Reduced and Bacterially Tested Platelet Components: A US Hospital Budget Impact Model.

BACKGROUND: US FDA draft guidance includes pathogen reduction (PR) or secondary rapid bacterial testing (RT) in its recommendations for mitigating risk of platelet component (PC) bacterial contamination. An interactive budget impact model was created for hospitals to use when considering these technologies. METHODS: A Microsoft Excel model was built and populated with base-case costs and probabilities identified through literature search and a survey of US hospital transfusion service directors. Annual costs of PC acquisition, testing, wastage, dispensing/transfusion, sepsis, shelf life, and reimbursement for a mid-sized hospital that purchases all of its PCs were compared for four scenarios: 100% conventional PCs (C-PC), 100% RT-PC, 100% PR-PC, and 50% RT-PC/50% PR-PC. RESULTS: Annual total costs were US$3.64, US$3.67, and US$3.96 million when all platelets were C-PC, RT-PC, or PR-PC, respectively, or US$3.81 million in the 50% RT-PC/50% PR-PC scenario. The annual net cost of PR-PC, obtained by subtracting annual reimbursements from annual total costs, is 6.18% above that of RT-PC. Maximum usable shelf lives for C-PC, RT-PC, and PR-PC are 3.0, 5.0, and 3.6 days, respectively; hospitals obtain PR-PC components earliest at 1.37 days. CONCLUSION: The model predicts minimal cost increase for PR-PC versus RT-PC, including cost offsets such as elimination of bacterial detection and irradiation, and reimbursement. Additional safety provided by PR, including risk mitigation of transfusion-transmission of a broad spectrum of viruses, parasites, and emerging pathogens, may justify this increase. Effective PC shelf life may increase with RT, but platelets can be available sooner with PR due to elimination of bacterial detection, depending on blood center logistics.

Use of a model for A1c formation to estimate average glucose operative between short-interval measurements of %A1c.

BACKGROUND: Estimated average glucose (AG) is generally reported along with hemoglobin A1c measurements according to a standard calculation. Given a normal red blood cell lifetime of 120 days, serial A1c measurements at intervals <120 days are not completely independent. For short interval measurements, a change in AG (ΔAG) necessarily underestimates the change in average glucose operative during the interval (ΔG). We use a model for kinetics of HbA1c to evaluate the theoretical relationship between ΔAG and ΔG for HbA1c measurements made at intervals between 0 and 120 days. METHODS: From any given starting point for A1c, step changes in G were simulated using model calculations to determine the extent to which A1c could change as a function of the interval of exposure. Values for ΔAG were compared to the operative ΔG as a function of the interval between A1c measurements. RESULTS: Results of model simulations are a single graph for relationship of ΔAG to ΔG as a function of the interval between A1c measurements. ΔAG for (15, 30, 45, 60, 76, and 90) day intervals underestimated operative ΔG by (73, 51, 34, 21, 11, and 5)%, respectively. CONCLUSIONS: Model calculations predict the relationship between changes in estimated average glucose to changes in operative glucose for serial A1c measurements made at intervals <120 days. Given that serial measurements of A1c made at short intervals are not uncommon in practice, physicians may find this information to be useful.

The first evaluation of formaldehyde column observations by improved Pandora spectrometers during the KORUS-AQ field study.

The Korea-United States Air Quality Study (KORUS-AQ) conducted during May-June 2016 offered the first opportunity to evaluate direct-sun observations of formaldehyde (HCHO) total column densities with improved Pandora spectrometer instruments. The measurements highlighted in this work were conducted both in the Seoul megacity area at the Olympic Park site (37.5232° N, 27.1260° E; 26 ma.s.l.) and at a nearby rural site downwind of the city at the Mount Taehwa research forest site (37.3123° N, 127.3106° E; 160ma.s.l.). Evaluation of these measurements was made possible by concurrent ground-based in situ observations of HCHO at both sites as well as overflight by the NASA DC-8 research aircraft. The flights provided in situ measurements of HCHO to characterize its vertical distribution in the lower troposphere (0-5km). Diurnal variation in HCHO total column densities followed the same pattern at both sites, with the minimum daily values typically observed between 6:00 and 7:00 local time, gradually increasing to a maximum between 13:00 and 17:00 before decreasing into the evening. Pandora vertical column densities were compared with those derived from the DC-8 HCHO in situ measured profiles augmented with in situ surface concentrations below the lowest altitude of the DC-8 in proximity to the ground sites. A comparison between 49 column densities measured by Pandora vs. aircraft-integrated in situ data showed that Pandora values were larger by 16% with a constant offset of 0.22DU (Dobson units; R 2 = 0.68). Pandora HCHO columns were also compared with columns calculated from the surface in situ measurements over Olympic Park by assuming a well-mixed lower atmosphere up to a ceilometer-measured mixed-layer height (MLH) and various assumptions about the small residual HCHO amounts in the free troposphere up to the tropopause. The best comparison (slope = 1.03±0.03; intercept = 0.29±0.02DU; and R 2 = 0.78±0.02) was achieved assuming equal mixing within ceilometer-measured MLH combined with an exponential profile shape. These results suggest that diurnal changes in HCHO surface concentrations can be reasonably estimated from the Pandora total column and information on the mixed-layer height. More work is needed to understand the bias in the intercept and the slope relative to columns derived from the in situ aircraft and surface measurements.

Validation of a New Method to Automatically Select Cases With Intraoperative Red Blood Cell Transfusion for Audit.

BACKGROUND: Hospitals review allogeneic red blood cell (RBC) transfusions for appropriateness. Audit criteria have been published that apply to 5 common procedures. We expanded on this work to study the management decision of selecting which cases involving transfusion of at least 1 RBC unit to audit (review) among all surgical procedures, including those previously studied. METHODS: This retrospective, observational study included 400,000 cases among 1891 different procedures over an 11-year period. There were 12,616 cases with RBC transfusion. We studied the proportions of cases that would be audited based on criteria of nadir hemoglobin (Hb) greater than the hospital's selected transfusion threshold, or absent Hb or missing estimated blood loss (EBL) among procedures with median EBL <500 mL. This threshold EBL was selected because it is approximately the volume removed during the donation of a single unit of whole blood at a blood bank. Missing EBL is important to the audit decision for cases in which the procedures' median EBL is <500 mL because, without an indication of the extent of bleeding, there are insufficient data to assume that there was sufficient blood loss to justify the transfusion. RESULTS: Most cases (>50%) that would be audited and most cases (>50%) with transfusion were among procedures with median EBL <500 mL (P < .0001). Among cases with transfusion and nadir Hb >9 g/dL, the procedure's median EBL was <500 mL for 3.0 times more cases than for procedures having a median EBL ≥500 mL. A greater percentage of cases would be recommended for audit based on missing values for Hb and/or EBL than based on exceeding the Hb threshold among cases of procedures with median EBL ≥500 mL (P < .0001). There were 3.7 times as many cases with transfusion that had missing values for Hb and/or EBL than had a nadir Hb >9 g/dL and median EBL for the procedure ≥500 mL. CONCLUSIONS: An automated process to select cases for audit of intraoperative transfusion of RBC needs to consider the median EBL of the procedure, whether the nadir Hb is below the hospital's Hb transfusion threshold for surgical cases, and the absence of either a Hb or entry of the EBL for the case. This conclusion applies to all surgical cases and procedures.

Carcinogenicity assessment of baricitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats.

Baricitinib is a potent and selective Janus kinase (JAK)1 and JAK2 inhibitor, and is approved for the treatment of moderately to severely active RA in adults in Europe, Japan, and other countries. This study evaluated the carcinogenic potential of baricitinib in Tg. rasH2 mice and Sprague-Dawley (Crl:CD) rats. Baricitinib was administered daily by oral gavage to Crl:CD rats for up to 94 weeks (dose levels of 0, 1, 3, or 8 mg/kg for males and 0, 3, 8, or 25 mg/kg for females) and to Tg. rasH2 mice for 26 weeks (dose levels of 0, 15, 40, or 300 mg/kg for males and 0, 10, 30, or 150 mg/kg for females). Baricitinib was well tolerated with no incidence of compound-related neoplasms at any dose levels in rats and mice. In mice, non-neoplastic events observed were bone marrow hypocellularity and increased adipocytes. In rats, baricitinib administration was associated with a dose-dependent increase in survival, with a decreased incidence of neoplasm (hematopoietic and mammary), potentially secondary to drug-related decreased weight gain. The incidence of proliferative changes such as neoplastic and hyperplastic lesions in the mammary glands of females and in the livers of males and females also decreased. In conclusion, baricitinib is not considered to be carcinogenic.

Average glucose from hemoglobin A1c for altered red blood cell lifetimes: Predictions based on a model for hemoglobin A1c formation.

BACKGROUND: A model for hemoglobin A1c (HbA1c) formation was used to predict the relationship between average glucose (AG) and %HbA1c under conditions of altered red blood cell lifetime (RCL). METHODS: Using a kinetic mass balance model for formation of HbA1c in red blood cells as a function of age (time in circulation), whole blood %HbA1c vs. glucose was calculated based on the nonlinear distribution of red blood cells as a function of age across RCL. RESULTS: Model calculations provided a close fit to the standard relationship of estimated average glucose to %HbA1c for normal RCL (r>0.999). Results for altered RCL were calculated assuming simple time-scale compression or expansion of the distribution of red blood cells as a function of RCL. For a given %HbA1c, the operative average glucose needed to have achieved a given %HbA1c was predicted to be altered by RCL according to average glucose×RCL=constant. CONCLUSIONS: Model calculations estimate the extent to which standard reporting of AG vs. HbA1c underestimates or overestimates AG under conditions of altered RCL. Conditions of altered RCL may often be operative in patients with certain hemoglobin variants.

Does therapeutic plasma exchange have a role in the treatment of prosthetic hip-associated cobalt toxicity? A case report and literature review.

BACKGROUND: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described. Given that cobalt is predominantly albumin bound, it should theoretically be removed by TPE. Here we report a case of PHACT and our experience using TPE to lower plasma cobalt levels. CASE REPORT: A 61-year-old woman developed deafness, blindness, ambulatory dysfunction, and endocrinopathies after MoM implant. Cobalt levels on admission were greater than 1500 µg/L. In an attempt to rapidly lower cobalt levels before MoM explant, hemodialysis and TPE were performed. Hemodialysis removed negligible amounts of cobalt. One session of TPE temporarily removed approximately two-thirds of measurable cobalt, but levels rebounded to pre-TPE values after 8 hours. It was only after MoM removal that cobalt levels plateaued below 300 µg/L and clinical symptoms improved. DISCUSSION: TPE removed cobalt from a PHACT patient, but a durable decrease in cobalt was only achieved after MoM explant. These findings are comparable to reports where chelation was employed in PHACT patients before MoM explant. The observed rebound phenomenon is likely from rapid equilibration between the immense extravascular tissue source (the MoM) and the intravascular compartment. CONCLUSION: TPE may serve as adjunctive therapy for PHACT patients whose cobalt levels remain high after explant, especially in patients with renal failure, in whom chelation is contraindicated.