Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

Regional impact assessment of air quality improvement: The air quality lifecourse assessment tool (AQ-LAT) for the West Midlands combined authority (WMCA) area.

Poor air quality is the largest environmental health risk in England. In the West Midlands, UK, ∼2.9 million people are affected by air pollution with an average loss in life expectancy of up to 6 months. The 2021 Environment Act established a legal framework for local authorities in England to develop regional air quality plans, generating a policy need for predictive environmental impact assessment tools. In this context, we developed a novel Air Quality Lifecourse Assessment Tool (AQ-LAT) to estimate electoral ward-level impacts of PM2.5 and NO2 exposure on outcomes of interest to local authorities, namely morbidity (asthma, coronary heart disease (CHD), stroke, lung cancer), mortality, and associated healthcare costs. We apply the Tool to assess the health economic burden of air pollutant exposure and estimate benefits that would be generated by meeting WHO 2021 Global Air Quality Guidelines (AQGs) (annual average concentrations) for NO2 (10 µg/m3) and PM2.5 (5 µg/m3) in the West Midlands Combined Authority Area. All West Midlands residents live in areas which exceed WHO AQGs, with 2070 deaths, 2070 asthma diagnoses, 770 CHD diagnoses, 170 lung cancers and 650 strokes attributable to air pollution exposure annually. Reducing PM2.5 and NO2 concentrations to WHO AQGs would save 10,700 lives reducing regional mortality by 1.8%, gaining 92,000 quality-adjusted life years (QALYs), and preventing 20,500 asthma, 7400 CHD, 1400 lung cancer, and 5700 stroke diagnoses, with economic benefits of £3.2 billion over 20 years. Significantly, we estimate 30% of QALY gains relate to reduced disease burden. The AQ-LAT has major potential to be replicated across local authorities in England and applied to inform regional investment decisions.

Assessment of CD8+ T-cell mediated immunity in an influenza A(H3N2) human challenge model in Belgium: a single centre, randomised, double-blind phase 2 study.

BACKGROUND: Protection afforded by inactivated influenza vaccines can theoretically be improved by inducing T-cell responses to conserved internal influenza A antigens. We assessed whether, in an influenza controlled human infection challenge, susceptible individuals receiving a vaccine boosting T-cell responses would exhibit lower viral load and decreased symptoms compared with placebo recipients. METHODS: In this single centre, randomised, double-blind phase 2 study, healthy adult (aged 18-55 years) volunteers with microneutralisation titres of less than 20 to the influenza A(H3N2) challenge strain were enrolled at an SGS quarantine facility in Antwerp, Belgium. Participants were randomly assigned double-blind using a permuted-block list with a 3:2 allocation ratio to receive 0·5 mL intramuscular injections of modified vaccinia Ankara (MVA) expressing H3N2 nucleoprotein (NP) and matrix protein 1 (M1) at 1·5 × 108 plaque forming units (4·3 × 108 50% tissue culture infectious dose [TCID50]; MVA-NP+M1 group) or saline placebo (placebo group). At least 6 weeks later, participants were challenged intranasally with 0·5 mL of a 1 × 106 TCID50/mL dose of influenza A/Belgium/4217/2015 (H3N2). Nasal swabs were collected twice daily from day 2 until day 11 for viral PCR, and symptoms of influenza were recorded from day 2 until day 11. The primary outcome was to determine the efficacy of MVA-NP+M1 vaccine to reduce the degree of nasopharyngeal viral shedding as measured by the cumulative viral area under the curve using a log-transformed quantitative PCR. This study is registered with ClinicalTrials.gov, NCT03883113. FINDINGS: Between May 2 and Oct 24, 2019, 145 volunteers were enrolled and randomly assigned to the MVA-NP+M1 group (n=87) or the placebo group (n=58). Of these, 118 volunteers entered the challenge period (71 in the MVA-NP+M1 group and 47 in the placebo group) and 117 participants completed the study (71 in the MVA-NP+M1 group and 46 in the placebo group). 78 (54%) of the 145 volunteers were female and 67 (46%) were male. The primary outcome, overall viral load as determined by quantitative PCR, did not show a statistically significant difference between the MVA-NP+M1 (mean 649·7 [95% CI 552·7-746·7) and placebo groups (mean 726·1 [604·0-848·2]; p=0·17). All reported treatment emergent adverse events (TEAEs; 11 in the vaccination phase and 51 in the challenge phase) were grade 1 and 2, except for two grade 3 TEAEs in the placebo group in the challenge phase. A grade 4 second trimester fetal death, considered possibly related to the MVA-NP+M1 vaccination, and an acute psychosis reported in a placebo participant during the challenge phase were reported. INTERPRETATION: The use of an MVA vaccine to expand CD4+ or CD8+ T cells to conserved influenza A antigens in peripheral blood did not affect nasopharyngeal viral load in an influenza H3N2 challenge model in seronegative, healthy adults. FUNDING: Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; and Barinthus Biotherapeutics.

Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

OBJECTIVE: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. DESIGN: Multicenter, retrospective, case-control study from 2017 to 2021. SETTING: Private referral center and veterinary teaching hospital. ANIMALS: One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI] = 0.90 [0.84-0.95], P < 0.0001) and PHS10 (AUC [95% CI] = 0.89 [0.81-0.97], P < 0.0001). PHS8 ≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10 ≥ 3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC] = 0.74 [95% CI: 0.66-0.80], n = 135). CONCLUSIONS: Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

The economic burden of burned patients for hospitalization in Canada.

BACKGROUND: Burn injuries pose a significant burden on both patients and healthcare systems. Yet, costs arising from the consumption of resources by these patients are rarely examined in Canada. OBJECTIVE: The objective of this study was to assess real-world costs resulting from the initial hospitalization of patients admitted to a major burn unit in Quebec, Canada. METHODS: A cost study based on a retrospective cohort was undertaken using in-hospital economic data matched to hospital chart data. Our cohort included all burn-injured patients admitted between April 1, 2017, and March 31, 2021, to the hospital's major burn unit during their initial hospitalization. Descriptive statistics were tabulated for sociodemographic and economic data. Costing data were analyzed unstratified and stratified according to burn severity (i.e., ≥ 20% of total body surface area [TBSA] vs. < 20%). Costs were presented in CAD 2021. RESULTS: Our cohort included 362 patients, including 65 (18%) with TBSA ≥ 20%. The average initial hospitalization cost was $32,360 ($22,783 for < 20% TBSA and $76,121 for ≥ 20% TBSA). CONCLUSION: Findings reveal that the total cost of the initial hospitalization, from a public hospital perspective, was $11,714,348. Our study underlines the substantial burden associated with burns and highlights the need for long-term cost evaluations.

Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis.

BACKGROUND: Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic disparities are evident within ALD; however, the precise nature of these disparities is poorly defined. METHODS: We conducted a search of the PubMed/MEDLINE and EMBASE databases to identify studies published from inception through September 2023 that reported ALD incidence, prevalence, and mortality within the United States, stratified by race and ethnicity. We calculated pooled prevalence and incidence by race and ethnicity, including risk ratios and ORs for ALD pooled prevalence and alcohol-associated hepatitis/alcohol-associated cirrhosis pooled proportions, and OR for ALD mortality using the DerSimonian and Laird method for random-effect models. RESULTS: We identified 25 relevant studies (16 for quantitative meta-analysis), comprising 76,867,544 patients. ALD prevalence was highest in Hispanic (4.5%), followed by White (3.1%) and Black (1.4%) individuals. Pooled risk ratios of ALD prevalence were 1.64 (95% CI: 1.12-2.39) for Hispanic and 0.59 (95% CI: 0.35-0.87) for Black compared to White individuals. Mortality among those with ALD did not significantly differ between White and Hispanic (OR: 1.54, 95% CI: 0.9-2.5; I2=0%), Black (OR: 1.2, 95% CI: 0.8-1.6; I2=0%), or Native American (OR: 2.41, 95% CI: 0.9-2.9) individuals, while there was a significant difference between White and Asian (OR: 0.1; 95% CI: 0.03-0.5) individuals. Most data were cross-sectional and assessed to be of poor or fair quality. CONCLUSIONS: Differences were observed in ALD epidemiology, including higher prevalence among Hispanic and lower prevalence among Black individuals, although there were smaller differences in ALD mortality. Differences in ALD prevalence and prognosis remain poorly defined based on existing data, highlighting a need for higher-quality epidemiological studies in this area.

Rural-urban disparities in the diagnosis and treatment of hypertension and diabetes among aging Indians.

INTRODUCTION: Hypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural-urban disparities in the diagnosis and treatment of these conditions among aging Indians. METHODS: Participants (n = 6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self-report and clinical/biochemical assessments, we subdivided participants with diabetes and hypertension into undiagnosed and untreated groups. Logistic regression and Fairlie decomposition analysis were the statistical methods utilized. RESULTS: There was a significant rural-urban disparity in undiagnosed hypertension (25.14%), untreated hypertension (11.75%), undiagnosed diabetes (16.94%), and untreated diabetes (11.62%). Further, sociodemographic and lifestyle factors, such as age and tobacco use were the common contributors to the disparities in both undiagnosed hypertension and undiagnosed diabetes, whereas education and body mass index (BMI) were significant contributors to the disparity in untreated hypertension. DISCUSSION: Rural Indians face significant healthcare disadvantages as compared to their urban counterparts, which prompts the urgent need for strategies for equitable healthcare.

Interrater reliability of photographic assessment of thyroid eye disease using the VISA classification.

PURPOSE: To determine the interrater reliability (IRR) of thyroid eye disease (TED) photographic assessment using the VISA classification. To assess whether a VISA grading atlas improves ophthalmology trainees' performance in photographic assessment of TED. METHODS: A prospective, partially randomized, international study conducted from September 2021 to May 2022. Online study invitation was emailed to a volunteer sample group of 68 ophthalmology college accredited consultants and trainees, and 6 were excluded from the study. Participants were asked to score 10 patient photographs of TED using only the inflammation and motility restriction components of the VISA classification. IRR was compared between groups of practitioners by their level of experience. A clinical activity grading atlas was randomized to 50% of the ophthalmology trainees. RESULTS: Overall rater ICC was 0.96 for inflammation and 0.99 for motility restriction. No statistically significant difference in IRR between rater groups was identified. Trainees with a grading atlas had the highest IRR for inflammation (ICC = 0.95). Each subcomponent of the inflammation and motility restriction components of VISA classification had an ICC considered good to excellent. The mean overall rater score was 4.6/9 for inflammation and 3.5/12 for motility restriction. For motility restriction there was a reduced mean score variance among all raters when scoring photographs with more severe motility restriction. CONCLUSION: IRR using the inflammation and motility restriction components of the VISA classification was excellent. A VISA grading atlas improved trainee performance in grading inflammation.

Access to athletic trainers and sex as modifiers of time to reach clinical milestones after sport-related concussion in collegiate athletes.

OBJECTIVE: Investigate whether an athlete's biological sex and exposure to a dedicated athletic trainer (AT) were related to clinical milestones after a sports-related concussion (SRC). DESIGN: Retrospective chart review. METHODS: Medical charts of collegiate athletes (n = 196 [70.9% female]) diagnosed with SRC were reviewed to extract: biological sex, dedicated AT exposure for their sport (yes/no), and time (days) to reaching clinical milestones (diagnosis, symptom resolution, unrestricted return to sport [RTS]). Mann-Whitney U tests were used to determine whether time to clinical milestones differed by sex, AT exposure, or their interaction. Proportions of same-day diagnoses and times to diagnosis, symptom resolution, and unrestricted RTS were evaluated with chi-squared and spearman's rank correlations, respectively. RESULTS: There were no significant differences in times to reaching any clinical milestone by sex, AT exposure, or their interaction (ps > 0.05). Forty-three percent of participants were diagnosed on the day of their SRC. This did not differ by sex or AT exposure (ps > 0.29). Longer times to SRC diagnosis were associated with more days to symptom resolution (ρ = 0.236, p = 0.001) and unrestricted RTS (ρ = 0.223, p < 0.001). CONCLUSIONS: Athlete sex and AT exposure were not associated with times to reach any clinical milestone; however, delayed diagnosis was associated with longer times to reach clinical recovery.

Psychosocial Risk Exposure Limits Routine Pediatric Oral Health Care.

Introduction: This study aimed to identify social, psychological, and contextual factors that influenced attendance at routine oral health visits in a cohort of 189 preschool children who were followed over a 2-year period. Methods: Generalized estimating equation was used to examine the association between clinic attendance and the predictors. ORs and 95% CIs were reported in the multiple logistic regression models. The study was conducted in Rochester, New York, between February 2016 and February 2021. Results: Prior to the COVID-19 pandemic declaration, the rate of canceled and no-show appointments was greater for routine clinic visits (20% and 24%, respectively) than for research visits (14% and 9%, respectively) for the same participants; these rates increased during the pandemic. After adjusting for sociodemographic factors, the likelihood of a canceled or no-show appointment was associated with parental depression (OR=1.06, CI=1.03, 1.09), regardless of the type or occurrence of the visit. Conclusions: Findings from this study demonstrate that attendance to oral health care in young children is reliably reduced with parental depression and that this may provide one mechanism for early emerging health inequalities of oral health.

Scope and Incentives for Risk Selection in Health Insurance Markets With Regulated Competition: A Conceptual Framework and International Comparison.

In health insurance markets with regulated competition, regulators face the challenge of preventing risk selection. This paper provides a framework for analyzing the scope (i.e., potential actions by insurers and consumers) and incentives for risk selection in such markets. Our approach consists of three steps. First, we describe four types of risk selection: (a) selection by consumers in and out of the market, (b) selection by consumers between high- and low-value plans, (c) selection by insurers via plan design, and (d) selection by insurers via other channels such as marketing, customer service, and supplementary insurance. In a second step, we develop a conceptual framework of how regulation and features of health insurance markets affect the scope and incentives for risk selection along these four dimensions. In a third step, we use this framework to compare nine health insurance markets with regulated competition in Australia, Europe, Israel, and the United States.

The Agreement Between Diagnoses as Stated by Patients and Those Contained in Routine Health Insurance Data.

BACKGROUND: The frequency of medical diagnoses is a figure of central importance in epidemiology and health services research. Prevalence estimates vary depending on the underlying data. For a better understanding of such discrepancies, we compared patients' diagnoses as reported by themselves in response to our questioning with their diagnoses as stated in the routine data of their health insurance carrier. METHODS: For 6558 adults insured by BARMER, one of the statutory health insurance carriers in Germany, we compared the diagnoses of various illnesses over a twelve-month period, as reported by the patients themselves in response to our questioning (October to December 2021), with their ICD-10-based diagnosis codes (Q4/2020-Q3/2021). The degree of agreement was assessed with two kappa values, sensitivity, and specificity. RESULTS: The patients' stated diagnoses of diabetes and hypertension agreed well or very well with their diagnosis codes, with kappa and PABAK values near 0.8, as well as very high sensitivity and specificity. Moderately good agreement with respect to kappa was seen for the diagnoses of heart failure (0.4), obesity, anxiety disorder, depression, and coronary heart disease (0.5 each). The poorest agreement (kappa ≤ 0.3) was seen for posttraumatic stress disorder, alcohol-related disorder, and mental and somatoform disorder. Agreement was worse with increasing age. CONCLUSION: Diagnoses as stated by patients often differ from those found in routine health insurance data. Discrepancies that can be considered negligible were found for only two of the 11 diseases that we studied. Our investigation confirms that these two sources of data yield different estimates of prevalence. Age is a key factor; further reasons for the discrepancies should be investigated, and avoidable causes should be addressed.

Demographics and Early Outcomes of Commercial Antibiotic Cement Usage for Infection Prophylaxis During Primary Total Knee Arthroplasty in Patients Older Than 65 Years: An American Joint Replacement Registry Study.

INTRODUCTION: The use of antibiotic-laden bone cement (ALBC) for infection prophylaxis in the setting of primary total knee arthroplasty (TKA) remains controversial. Using data from the American Joint Replacement Registry (AJRR), (1) we examined the demographics of ALBC usage in the United States and (2) identified the effect of prophylactic commercially available ALBC on early revision and readmission for prosthetic joint infection (PJI) after primary TKA. METHODS: This is a retrospective cohort study of the AJRR from 2017 to 2020. Patients older than 65 years undergoing primary cemented TKA with or without the use of commercially available antibiotic cement were eligible for inclusion (N = 251,506 patients). Data were linked to available Medicare claims to maximize revision outcomes. Demographics including age, sex, race/ethnicity, Charlson Comorbidity Index (CCI), preoperative inflammatory arthritis, region, and body mass index (BMI) class were recorded. Cox proportional hazards regression analysis was used to evaluate the association between the two outcome measures and ALBC usage. RESULTS: Patients undergoing cemented TKA with ALBC were more likely to be Non-Hispanic Black ( P < 0.001), have a CCI of 2 or 3 ( P < 0.001), reside in the South ( P < 0.001), and had a higher mean BMI ( P < 0.001). In the regression models, ALBC usage was associated with increased risk of 90-day revision for PJI (hazards ratio 2.175 [95% confidence interval] 1.698 to 2.787) ( P < 0.001) and was not associated with 90-day all-cause readmissions. Male sex, higher CCI, and BMI >35 were all independently associated with 90-day revision for PJI. DISCUSSION: The use of commercial ALBC in patients older than 65 years for primary TKA in the AJRR was not closely associated with underlying comorbidities suggesting that hospital-level and surgeon-level factors influence its use. In addition, ALBC use did not decrease the risk of 90-day revision for PJI and was not associated with 90-day readmission rates.

Impact of Medicaid Expansion and Firearm Legislation on Cost of Firearm Injuries.

INTRODUCTION: Firearm injury-related hospitalizations in the U.S. cost $900 million annually. Before the Affordable Care Act, government insurance programs covered 41% of the costs. This study describes the impact of Affordable Care Act Medicaid expansion and state-level firearm legislation on coverage and costs for firearm injuries. METHODS: This cross-sectional study included 35,854,586 hospitalizations from 27 states in 2013 and 2016. Data analyses were performed in 2022. Firearm injuries were classified by mechanism: assault, unintentional, self-harm, or undetermined. The impact of the Affordable Care Act expansion was determined using difference-in-differences analysis. Differences in per capita costs between states with stronger and weak firearm legislation were compared using univariable and multivariable analyses. RESULTS: The authors identified 31,451 initial firearm injury-related hospitalizations. In states with weak firearm legislation, hospitalization costs per 100,000 residents were higher from unintentional ($25,834; p=0.04) and self-inflicted ($11,550; p=0.02) injuries; there were no state-level differences in assault or total per capita firearm-related hospitalization costs. Affordable Care Act expansion increased government coverage of costs by 15 percentage points (95% CI=3, 29) and decreased costs to uninsured/self-pay by 14 percentage points (95% CI=6, 21). In 2016, states with weak firearm legislation and no Affordable Care Act expansion had the highest proportion of hospitalization costs attributed to uninsured/self-pay patients (24%, 95% CI=15, 34). CONCLUSIONS: Affordable Care Act expansion increased government coverage of hospitalizations for firearm injuries. Unintentional and self-harm costs were significantly higher for states with weak firearm legislation. States with weak firearm legislation that did not expand Medicaid had the highest proportion of uninsured/self-pay patients.

Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study.

BACKGROUND: Patients with relapsed/refractory multiple myeloma are at increased risk of infection. Infections during treatment with teclistamab, the first B-cell maturation antigen-directed bispecific antibody approved for triple-class-exposed relapsed/refractory multiple myeloma, was examined in the phase 1/2 MajesTEC-1 study. METHODS: Patients (N = 165) received subcutaneous teclistamab 1.5 mg/kg weekly after a step-up dosing schedule (0.06 mg/kg and 0.3 mg/kg, each separated by 2-4 days). Patients were monitored frequently for infections; prophylaxis and management were per institutional guidelines. RESULTS: At a median follow-up of 22.8 months (range, 0.3-33.6), infections were reported in 132 patients (80.0%). Grade 3/4 infections occurred in 91 patients (55.2%), including COVID-19 (21.2%), respiratory infections (19.4%), Pneumocystis jirovecii pneumonia (4.2%), viral infections (4.2%), and gastrointestinal infections (1.2%). Twenty-one patients died from infections (18 from COVID-19). Median time to first onset of any-grade and grade 3 to 5 infections was 1.7 and 4.2 months, respectively. Overall, 70.9% of patients had ≥1 postbaseline immunoglobulin G (IgG) level <400 mg/dL; median time to IgG <400 mg/dL was 1.2 months (range, 0.2-19.8) and 46.1% received ≥1 dose of IgG replacement. Grade 3/4 neutropenia occurred in 65.5% of patients (median time to grade ≥3 neutropenia/febrile neutropenia was 2.3 months [range, 0-18.1]). CONCLUSION: Based on the infection profile of B-cell maturation antigen-targeted bispecific antibodies such as teclistamab, it is recommended that clinicians and patients remain vigilant for a range of infection types throughout treatment to facilitate prompt intervention. Appropriate screening, prophylaxis, and management of infections, hypogammaglobulinemia, and neutropenia are important. CLINICAL TRIAL REGISTRATION: NCT03145181/NCT04557098 (ClinicalTrials.gov) PLAIN LANGUAGE SUMMARY: Before starting teclistamab, patients should be up to date with vaccinations (including COVID-19) and screened for hepatitis B and C and HIV. Teclistamab should not be given to patients with any active infections. Prophylactic antimicrobials should be administered per institutional guidelines. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes simplex/varicella zoster virus is recommended during teclistamab treatment. Close monitoring of infections and immunoglobulin G (IgG) levels should continue throughout teclistamab treatment. IgG replacement (administered every 3-6 weeks) should be used to maintain IgG ≥400 mg/dL. Growth factors should be considered for grade ≥3 neutropenia with infection/fever and grade 4 neutropenia.

Associations Between Lean IT Management and Financial Performance in US Hospitals.

BACKGROUND AND OBJECTIVES: To understand the relationship between Lean implementation in information technology (IT) departments and hospital performance, particularly with respect to operational and financial outcomes. METHODS: Primary data were sourced from 1222 hospitals that responded to the National Survey of Lean (NSL)/Transformational Performance Improvement, which was fielded to 4500 general medical-surgical hospitals across the United States. Secondary sources included hospital performance data from the Agency for Healthcare Research and Quality (AHRQ) and the Centers for Medicare & Medicaid Services (CMS). We performed 2 sets of multivariable regressions using data gathered from US hospitals, linked to AHRQ and CMS performance outcomes. We examined 10 different outcomes measuring financial performance, quality of care, and patient experience, and their associations with Lean adoption within hospital IT departments. We then focused only on those hospitals that adopted Lean in IT to identify specific practices associated with performance. RESULTS: Controlling for other factors, adoption of Lean IT management was associated with lower length of stay ( b = -0.098, P = .018) and inpatient expense per discharge ( b = -0.112, P = .090). Specifically, use of visual management tools (eg, A3 storyboards, status sheets) was associated with lower adjusted inpatient expense per discharge ( b = -0.176, P = .034) and higher earnings before interest, taxes, depreciation, and amortization margin ( b = 0.124, P = .042). Such tools were also associated with hospital participation in bundled payment programs (odds ratio = 2.326; P = .046; 95% confidence interval, 0.979-5.527) and percentage of net revenue paid on a shared risk basis ( b = 0.188, P = .031). CONCLUSIONS: Lean IT management was associated with positive financial performance, particularly with hospital participation in value-based payment. More detailed study is needed to understand other influential factors and types of work processes, activities, or mechanisms by which high-functioning IT can contribute to financial outcomes.

Savings in CT Net Scan Energy Consumption: Assessment Using Dose Report Metrics and Comparison With Savings in Idle State Energy Consumption.

BACKGROUND. CT scanners' net scan state (i.e., image acquisition period) represents a potential target for energy savings through protocol adjustments. However, gauging CT energy savings is difficult without installing costly energy monitors. OBJECTIVE. The purpose of this article was to assess correlations between CT dose report metrics and energy consumption during the system net scan state and to compare theoretic energy savings from matching percentage reductions in energy consumption during net scan and idle system states. METHODS. Current sensors were installed on a single CT scanner. A phantom was scanned at varying kilovoltage settings and effective tube current-rotation time settings. A retrospective assessment was performed in 32 patients (mean age, 61.2 ± 17.9 [SD] years; 17 men, 15 women) who underwent 32 single-energy noncontrast abdominopelvic CT examinations from September 22, 2021, to September 27, 2021, on the same scanner. Correlations between dose report metrics and net scan energy consumption were assessed in the phantom and clinical scans, and equations were generated to derive net scan energy consumption from DLP. An additional retrospective assessment was performed in 1355 patients (mean age, 59.3 ± 16.9 years; 663 men, 692 women) who underwent 1728 single-energy noncontrast abdominopelvic CT examinations from January 1, 2021, through December 31, 2021, on the same scanner to estimate net scan energy consumption per examination. This information was integrated with literature-derived values to compare estimated annual national energy savings resulting from 20% reductions in net scan and idle state energy consumption. RESULTS. Net scan energy consumption in the phantom scans showed high linear correlation with DLP (R2 = 0.87), and, in the clinical scans, high linear correlation with CTDIvol (R2 = 0.89) and very high linear correlation with DLP (R2 = 0.92). When combining mean DLP in examinations performed in the 1-year interval, an equation relating DLP and net scan energy consumption and literature values estimated that annual national energy savings was 14.9 times greater (40,437,870 kWh/2,704,000 kWh) by targeting the idle state rather than net scan state. CONCLUSION. CT net scan energy savings can be inferred from reductions in dose report metrics. However, targeting net scan energy consumption has modest impact relative to targeting idle state energy consumption. CLINICAL IMPACT. Environmental sustainability efforts should target the idle state energy consumption of CT.

Wildlife ecological risk assessment in the 21st century: Promising technologies to assess toxicological effects.

Despite advances in toxicity testing and the development of new approach methodologies (NAMs) for hazard assessment, the ecological risk assessment (ERA) framework for terrestrial wildlife (i.e., air-breathing amphibians, reptiles, birds, and mammals) has remained unchanged for decades. While survival, growth, and reproductive endpoints derived from whole-animal toxicity tests are central to hazard assessment, nonstandard measures of biological effects at multiple levels of biological organization (e.g., molecular, cellular, tissue, organ, organism, population, community, ecosystem) have the potential to enhance the relevance of prospective and retrospective wildlife ERAs. Other factors (e.g., indirect effects of contaminants on food supplies and infectious disease processes) are influenced by toxicants at individual, population, and community levels, and need to be factored into chemically based risk assessments to enhance the "eco" component of ERAs. Regulatory and logistical challenges often relegate such nonstandard endpoints and indirect effects to postregistration evaluations of pesticides and industrial chemicals and contaminated site evaluations. While NAMs are being developed, to date, their applications in ERAs focused on wildlife have been limited. No single magic tool or model will address all uncertainties in hazard assessment. Modernizing wildlife ERAs will likely entail combinations of laboratory- and field-derived data at multiple levels of biological organization, knowledge collection solutions (e.g., systematic review, adverse outcome pathway frameworks), and inferential methods that facilitate integrations and risk estimations focused on species, populations, interspecific extrapolations, and ecosystem services modeling, with less dependence on whole-animal data and simple hazard ratios. Integr Environ Assess Manag 2024;20:725-748. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

A spatiotemporally explicit modeling approach for more realistic exposure and risk assessment of off-field soil organisms.

Natural and seminatural habitats of soil living organisms in cultivated landscapes can be subject to unintended exposure by active substances of plant protection products (PPPs) used in adjacent fields. Spray-drift deposition and runoff are considered major exposure routes into such off-field areas. In this work, we develop a model (xOffFieldSoil) and associated scenarios to estimate exposure of off-field soil habitats. The modular model approach consists of components, each addressing a specific aspect of exposure processes, for example, PPP use, drift deposition, runoff generation and filtering, estimation of soil concentrations. The approach is spatiotemporally explicit and operates at scales ranging from local edge-of-field to large landscapes. The outcome can be aggregated and presented to the risk assessor in a way that addresses the dimensions and scales defined in specific protection goals (SPGs). The approach can be used to assess the effect of mitigation options, for example, field margins, in-field buffers, or drift-reducing technology. The presented provisional scenarios start with a schematic edge-of-field situation and extend to real-world landscapes of up to 5 km × 5 km. A case study was conducted for two active substances of different environmental fate characteristics. Results are presented as a collection of percentiles over time and space, as contour plots, and as maps. The results show that exposure patterns of off-field soil organisms are of a complex nature due to spatial and temporal variabilities combined with landscape structure and event-based processes. Our concepts and analysis demonstrate that more realistic exposure data can be meaningfully consolidated to serve in standard-tier risk assessments. The real-world landscape-scale scenarios indicate risk hot-spots that support the identification of efficient risk mitigation. As a next step, the spatiotemporally explicit exposure data can be directly coupled to ecological effect models (e.g., for earthworms or collembola) to conduct risk assessments at biological entity levels as required by SPGs. Integr Environ Assess Manag 2024;20:263-278. © 2023 Applied Analysis Solutions LLC and WSC Scientific GmbH and Bayer AG and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma.

OBJECTIVES: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin's lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting. METHODS: We used a decision-analytic semi-Markov model with four health states and 1-month cycles. Resource use was prospectively collected in the Inter-B-NHL ritux 2010 trial (NCT01516580). Transition probabilities were assessed from patient-level data from the trial (n = 328). In the base case analysis, direct medical costs from the French National Insurance Scheme and life-years (LYs) were computed in both arms over a 3-year time horizon. Incremental net monetary benefit and cost-effectiveness acceptability curve were computed through a probabilistic sensitivity analysis. Deterministic sensitivity analysis and several sensitivity analyses on key assumptions were also conducted, including one exploratory analysis with quality-adjusted life years as the health outcome. RESULTS: OS and EFS benefits shown in the Inter-B-NHL ritux 2010 trial translated into the model by rituximab-chemotherapy being the most effective and also the least expensive strategy over the chemotherapy strategy. The mean difference in LYs between arms was 0.13 [95% CI 0.02; 0.25], and the mean cost difference € - 3 710 [95% CI € - 17,877; € 10,525] in favor of rituximab-chemotherapy group. For a € 50,000 per LY willingness-to-pay threshold, the probability of the rituximab-chemotherapy strategy being cost-effective was 91.1%. All sensitivity analyses confirmed these findings. CONCLUSION: Adding rituximab to LMB chemotherapy in children and adolescents with high-risk mature B-cell non-Hodgkin's lymphoma is highly cost-effective in France. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01516580.