Cost-Effectiveness of Plasma Microbial Cell-Free DNA Sequencing When Added to Usual Care Diagnostic Testing for Immunocompromised Host Pneumonia.

INTRODUCTION: Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value. AIM: The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients. METHODS: A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0. CONCLUSIONS: Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes.

Quantifying cost of disease in livestock: a new metric for the Global Burden of Animal Diseases.

BACKGROUND: Increasing awareness of the environmental and public health impacts of expanding and intensifying animal-based food and farming systems creates discord, with the reliance of much of the world's population on animals for livelihoods and essential nutrition. Increasing the efficiency of food production through improved animal health has been identified as a step towards minimising these negative effects without compromising global food security. The Global Burden of Animal Diseases (GBADs) programme aims to provide data and analytical methods to support positive change in animal health across all livestock and aquaculture animal populations. METHODS: In this study, we present a metric that begins the process of disease burden estimation by converting the physical consequences of disease on animal performance to farm-level costs of disease, and calculates a metric termed the Animal Health Loss Envelope (AHLE) via comparison between the status quo and a disease-free ideal. An example calculation of the AHLE metric for meat production from broiler chickens is provided. FINDINGS: The AHLE presents the direct financial costs of disease at farm-level for all causes by estimating losses and expenditure in a given farming system. The general specification of the model measures productivity change at farm-level and provides an upper bound on productivity change in the absence of disease. On its own, it gives an indication of the scale of total disease cost at farm-level. INTERPRETATION: The AHLE is an essential stepping stone within the GBADs programme because it connects the physical performance of animals in farming systems under different environmental and management conditions and different health states to farm economics. Moving forward, AHLE results will be an important step in calculating the wider monetary consequences of changes in animal health as part of the GBADs programme. FUNDING: Bill & Melinda Gates Foundation, the UK Foreign, Commonwealth and Development Office, EU Horizon 2020 Research and Innovation Programme.

Assessment of cerebral drug occupancy in humans using a single PET-scan: A [11C]UCB-J PET study.

PURPOSE: Here, we evaluate a PET displacement model with a Single-step and Numerical solution in healthy individuals using the synaptic vesicle glycoprotein (SV2A) PET-tracer [11C]UCB-J and the anti-seizure medication levetiracetam (LEV). We aimed to (1) validate the displacement model by comparing the brain LEV-SV2A occupancy from a single PET scan with the occupancy derived from two PET scans and the Lassen plot and (2) determine the plasma LEV concentration-SV2A occupancy curve in healthy individuals. METHODS: Eleven healthy individuals (five females, mean age 35.5 [range: 25-47] years) underwent two 120-min [11C]UCB-J PET scans where an LEV dose (5-30 mg/kg) was administered intravenously halfway through the first PET scan to partially displace radioligand binding to SV2A. Five individuals were scanned twice on the same day; the remaining six were scanned once on two separate days, receiving two identical LEV doses. Arterial blood samples were acquired to determine the arterial input function and plasma LEV concentrations. Using the displacement model, the SV2A-LEV target engagement was calculated and compared with the Lassen plot method. The resulting data were fitted with a single-site binding model. RESULTS: SV2A occupancies and VND estimates derived from the displacement model were not significantly different from the Lassen plot (p = 0.55 and 0.13, respectively). The coefficient of variation was 14.6% vs. 17.3% for the Numerical and the Single-step solution in Bland-Altman comparisons with the Lassen plot. The average half maximal inhibitory concentration (IC50), as estimated from the area under the curve of the plasma LEV concentration, was 12.5 µg/mL (95% CI: 5-25) for the Single-Step solution, 11.8 µg/mL (95% CI: 4-25) for the Numerical solution, and 6.3 µg/mL (95% CI: 0.08-21) for the Lassen plot. Constraining Emax to 100% did not significantly improve model fits. CONCLUSION: Plasma LEV concentration vs. SV2A occupancy can be determined in humans using a single PET scan displacement model. The average concentration of the three computed IC50 values ranges between 6.3 and 12.5 µg/mL. The next step is to use the displacement model to evaluate LEV occupancy and corresponding plasma concentrations in relation to treatment efficacy. CLINICAL TRIAL REGISTRATION: NCT05450822. Retrospectively registered 5 July 2022 https://clinicaltrials.gov/ct2/results? term=NCT05450822&Search=Search.

New evidence on the impacts of cross-market hospital mergers on commercial prices and measures of quality.

OBJECTIVE: To examine the impact of "cross-market" hospital mergers on prices and quality and the extent to which serial acquisitions contribute to any measured effects. DATA SOURCES: 2009-2017 commercial claims from the Health Care Cost Institute (HCCI) and quality measures from Hospital Compare. STUDY DESIGN: Event study models in which the treated group consisted of hospitals that acquired hospitals further than 50 miles, and the control group was hospitals that were not part of any merger activity (as a target or acquirer) during the study period. DATA EXTRACTION METHODS: We extracted data for 214 treated hospitals and 955 control hospitals. PRINCIPAL FINDINGS: Six years after acquisition, cross-market hospital mergers had increased acquirer prices by 12.9% (CI: 0.6%-26.6%) relative to control hospitals, but had no discernible impact on mortality and readmission rates for heart failure, heart attacks and pneumonia. For serial acquirers, the price effect increased to 16.3% (CI: 4.8%-29.1%). For all acquisitions, the price effect was 21.8% (CI: 4.6%-41.7%) when the target's market share was greater than the acquirer's market share versus 9.7% (CI: -0.5% to 20.9%) when the opposite was true. The magnitude of the price effect was similar for out-of-state and in-state cross-market mergers. CONCLUSIONS: Additional evidence on the price and quality effects of cross-market mergers is needed at a time when over half of recent hospital mergers have been cross-market. To date, no hospital mergers have been challenged by the Federal Trade Commission on cross-market grounds. Our study is the third to find a positive price effect associated with cross-market mergers and the first to show no quality effect and how serial acquisitions contribute to the price effect. More research is needed to identify the mechanism behind the price effects we observe and analyze price effect heterogeneity.

Estimates of the Lifetime Productivity Costs of Chlamydia, Gonorrhea, and Syphilis in the United States.

BACKGROUND: Productivity costs of STIs reflect the value of lost time due to STI morbidity and mortality, including time spent travelling to, waiting for, and receiving STI treatment. The purpose of this study was to provide updated estimates of the average lifetime productivity cost for chlamydia, gonorrhea, and syphilis, per incident infection. METHODS: We adapted published decision tree models from recent studies of the lifetime medical costs of chlamydia, gonorrhea, and syphilis in the United States. For each possible outcome of infection, we applied productivity costs that we obtained based on published health economic studies. Productivity costs included the value of patient time spent to receive treatment for STIs and for related sequelae such as pelvic inflammatory disease in women. We used a human capital approach and included losses in market (paid) and non-market (unpaid) productivity. We conducted one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: The average lifetime productivity cost per infection was $28 for chlamydia in men, $205 for chlamydia in women, $37 for gonorrhea in men, $212 for gonorrhea in women, and $411 for syphilis regardless of sex, in 2023 US dollars. The estimated lifetime productivity costs of these STIs acquired in the United States in 2018 was $795 million. CONCLUSIONS: These estimates of the lifetime productivity costs can help in quantifying the overall economic burden of STIs in the United States beyond just the medical cost burden and can inform cost-effectiveness analyses of STI prevention activities.

AOA Critical Issues Symposium: The Dynamic Environment of Health Care.

ABSTRACT: The dynamic health-care environment continues to undergo disruptive change. As the health-care system emerges from the pandemic, underlying issues have progressively become critical. Private equity acquisition is dramatically increasing, and consolidation in the entire health-care system limits choice and access. Challenges in the workforce and supply chain persist, adding pressure on already strained health-care organizations. Innovative solutions are required to provide equitable value-based access to orthopaedic care.

Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults.

BACKGROUNDSanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODSThis randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV-) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/µL). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later.RESULTSThere were no solicited adverse events in the 9 HIV- and 12 HIV+ participants. After CHMI, 6 of 6 NS controls, 1 of 5 HIV- vaccinees, and 4 of 4 HIV+ vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ CD4+ T cell responses, and Vδ2+ γδ CD3+ T cells were nonsignificantly higher in HIV- than in HIV+ vaccinees. Sera from HIV- vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fcγ3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies.CONCLUSIONSPfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa.TRIAL REGISTRATIONClinicalTrials.gov NCT03420053.FUNDINGEquatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354-01.

An Interactive Modeling Tool for Projecting the Health and Direct Medical Cost Impact of Changes in the Sexually Transmitted Diseases Prevention Program Budgets.

CONTEXT: Estimating the return on investment for public health services, tailored to the state level, is critical for demonstrating their value and making resource allocation decisions. However, many health departments have limited staff capacity and expertise to conduct economic analyses in-house. PROGRAM: We developed a user-friendly, interactive Excel-based spreadsheet model that health departments can use to estimate the impact of increases or decreases in sexually transmitted infection (STI) prevention funding on the incidence and direct medical costs of chlamydia, gonorrhea, syphilis, and STI-attributable HIV infections. Users tailor results to their jurisdictions by entering the size of their population served; the number of annual STI diagnoses; their prior annual funding amount; and their anticipated new funding amount. The interface was developed using human-centered design principles, including focus groups with 15 model users to collect feedback on an earlier model version and a usability study on the prototype with 6 model users to finalize the interface. IMPLEMENTATION: The STI Prevention Allocation Consequences Estimator ("SPACE Monkey 2.0") model will be publicly available as a free downloadable tool. EVALUATION: In the usability testing of the prototype, participants provided overall positive feedback. They appreciated the clear interpretations, outcomes expressed as direct medical costs, functionalities to interact with the output and copy charts into external applications, visualization designs, and accessible information about the model's assumptions and limitations. Participants provided positive responses to a 10-item usability evaluation survey regarding their experiences with the prototype. DISCUSSION: Modeling tools that synthesize literature-based estimates and are developed with human-centered design principles have the potential to make evidence-based estimates of budget changes widely accessible to health departments.

Role of Lateral Extra-articular Tenodesis in Restraining Internal Tibial Rotation: In Vitro Biomechanical Assessment of Lateral Tissue Engagement.

BACKGROUND: The way in which force increases in the anterolateral tissues and the lateral extra-articular tenodesis (LET) tissue to resist internal rotation (IR) of the tibia after anterior cruciate ligament (ACL) reconstruction in isolation and after LET augmentation, respectively, is not well understood. PURPOSE: (1) To compare in a cadaveric model how force increases (ie, engages) in the anterolateral tissues with IR of the tibia after isolated ACL reconstruction and in the LET tissue after augmentation of the ACL reconstruction with LET and (2) to determine whether IR of the tibia is related to engagement of the LET tissue. STUDY DESIGN: Controlled laboratory study. METHODS: IR moments were applied to 9 human cadaveric knees at 0°, 30°, 60°, and 90° of flexion using a robotic manipulator. Each knee was tested in 2 states: (1) after isolated ACL reconstruction with intact anterolateral tissues and (2) after LET was performed using a modified Lemaire technique with the LET tissue fixed at 60° of flexion under 44 N of tension. Resultant forces carried by the anterolateral tissues and the LET tissue were determined via superposition. The way force increased in these tissues was characterized via parameters of tissue engagement, namely in situ slack, in situ stiffness, and tissue force at peak applied IR moment, and then compared (α < .05). IR was related to parameters of engagement of the LET tissue via simple linear regression (α < .05). RESULTS: The LET tissue exhibited less in situ slack than the anterolateral tissues at 30°, 60°, and 90° of flexion (P≤ .04) and greater in situ stiffness at 30° and 90° of flexion (P≤ .043). The LET tissue carried greater force at the peak applied IR moment at 0° and 30° of flexion (P≤ .01). IR was related to the in situ slack of the LET tissue (R2≥ 0.88; P≤ .0003). CONCLUSION: LET increased restraint to IR of the tibia compared with the anterolateral tissue, particularly at 30°, 60°, and 90° of flexion. IR of the tibia was positively associated with in situ slack of the LET tissue. CLINICAL RELEVANCE: Fixing the LET at 60° of flexion still provided IR restraint in the more functionally relevant flexion angle of 30°. Surgeons should pay close attention to the angle of internal and/or external tibial rotation when fixing the LET tissue intraoperatively because this surgical parameter is related to in situ slack of the LET tissue and, therefore, the amount of IR of the tibia.

Financial Vulnerability and Its Association with HIV Transmission Risk Behaviors Among People Who Inject Drugs in Kyrgyzstan.

The Family Resource Scale (FRS) is a three-factor financial vulnerability (FV) measure. FV may impact HIV transmission risks. Cross-sectional data from 279 people who inject drugs (PWID) in Kyrgyzstan surveyed April-October 2021 was used to validate the FRS and estimate associations between FV on past 6-month injection and sexual HIV risk outcomes. The three-factor FRS reflected housing, essential needs, and fiscal independence, and had good internal reliability and structural validity. Greater cumulative, housing, and essential needs FRS scores were associated with increased relative risk on public injection (adjusted risk ratio [aRR], 95% confidence interval [95% CI]: 1.03 [1.01, 1.04]; aRR [95% CI]: 1.06 [1.02, 1.09]; aRR [95% CI]: 1.06 [1.03, 1.08], respectively, all p < 0.001) and preparing injections with unsafe water sources (aRR [95% CI]: 1.04 [1.02, 1.07]; aRR [95% CI]: 1.09 [1.04, 1.15]; aRR [95% CI]: 1.08 [1.03, 1.14], respectively, all p < 0.001). Results suggest that PWID housing- and essential needs-related FV may exacerbate injection HIV transmission risks. Reducing PWIDs' FV may enhance the HIV response in Kyrgyzstan.

RESUMEN: La Escala de Recursos Familiares (FRS, por sus siglas en inglés) es una medida de vulnerabilidad financiera (FV, por sus siglas en inglés) de tres factores. La FV puede afectar los riesgos de transmisión del VIH. Se utilizaron datos transversales de 279 personas que se inyectan drogas (PWID, por sus siglas en inglés) en Kirguistán encuestadas de abril a octubre de 2021 para validar la FRS y estimar las asociaciones entre la FV en la inyección y los resultados de riesgo sexual del VIH en los últimos seis meses. La FRS de tres factores reflejaba la vivienda, las necesidades esenciales y la independencia fiscal, y presentaba una buena confiabilidad interna y validez estructural. Mayores puntajes acumulativos de la FRS en vivienda y necesidades esenciales se asociaron con un mayor riesgo relativo en la inyección pública (Riesgo relativo ajustada [aRR], Intervalo de Confianza del 95% [IC95%]: 1.03 [1.01, 1.04]; aRR [IC95%]: 1.06 [1.02, 1.09]; aRR [IC95%]: 1.06 [1.03, 1.08], respectivamente, todos p < 0.001) y la preparación de inyección con fuentes de agua no seguras (aRR [IC95%]: 1.04 [1.02, 1.07]; aRR [IC95%]: 1.09 [1.04, 1.15]; aRR [IC95%]: 1.08 [1.03, 1.14], respectivamente, todos p < 0.001). Los resultados sugieren que la FV relacionada con la vivienda y las necesidades esenciales de las PWID puede exacerbar los riesgos de transmisión del VIH por la inyección. Reducir la FV de las PWID puede mejorar la respuesta al VIH en Kirguistán.

Nutritional Assessment in Patients after Gastric Electrical Stimulation (GES).

BACKGROUND: Gastric electrical stimulation (GES) is used for patients with drug-refractory gastroparesis (Gp) symptoms. Approximately two-thirds of patients with Gp symptoms are either overweight or obese. We aimed to assess symptoms and nutritional status pre-GES and post-GES placement in a large sample of drug-refractory Gp patients. METHODS: We conducted a chart review of 282 patients with drug-refractory Gp who received temporary followed by permanent GES at an academic medical center. Gastrointestinal symptoms were collected by a traditional standardized PRO (0-4, 0 being asymptomatic and 4 being worst symptoms), baseline nutritional status by BMI plus subjective global assessment (SGA score A, B, C, for mild, moderate, and severe nutritional deficits), ability to tolerate diet, enteral tube access, and parenteral therapy were assessed at baseline and after permanent GES placement. RESULTS: Comparing baseline with permanent, GES was found to significantly improve upper GI symptoms in all quartiles. Of the 282 patients with baseline body mass index (BMI) information, 112 (40%) patients were severely malnourished at baseline, of which 36 (32%) patients' nutritional status improved after GES. Among all patients, 76 (68%) patients' nutritional status remained unchanged. Many patients with high BMI were malnourished by SGA. CONCLUSION: We conclude that symptomatic patients of different BMIs showed improvement in their GI symptoms irrespective of baseline nutritional status. Severely malnourished patients were found to have an improvement in their nutritional status after GES therapy. We conclude that BMI, even if high, is not by itself a contraindication for GES therapy for symptomatic patients.

Assessment of Obstructive Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease in Primary Care.

Study Objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments. Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at 2 primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of symptoms, treatment, or a referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment. Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a 1-year period. Positive associations with OSA assessment included body mass index ≥ 30 (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9). Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.

Patient Frailty is Correlated With Increased Adverse Events and Costs After Revision Knee Arthroplasty.

BACKGROUND: Frailty can predict adverse outcomes after various orthopaedic procedures, but is not well-studied in revision total knee arthroplasty (rTKA). We investigated the correlation between the Hospital Frailty Risk Score (HFRS) and post-rTKA outcomes. METHODS: Using the Nationwide Readmissions Database, we identified rTKA patients discharged from January 2017 to November 2019 for the most common diagnoses (mechanical loosening, infection, and instability). Using HFRS, we compared 30-day readmission rate, length of stay, and hospitalization cost between frail and nonfrail patients with multivariate and binomial regressions. The 30-day complication and reoperation rates were compared using univariate analyses. We identified 25,177 mechanical loosening patients, 12,712 infection patients, and 9,458 instability patients. RESULTS: Frail patients had higher rates of 30-day readmission (7.8 versus 3.7% for loosening, 13.5 versus 8.1% for infection, 8.7 versus 3.9% for instability; P < .01), longer length of stay (4.1 versus 2.4 days for loosening, 8.1 versus 4.4 days for infection, 4.9 versus 2.4 days for instability; P < .01), and greater cost ($32,082 versus $27,582 for loosening, $32,898 versus $28,115 for infection, $29,790 versus $24,164 for instability; P < .01). Frail loosening patients had higher 30-day complication (6.8 versus 2.9%, P < .01) and reoperation rates (1.8 versus 1.2%, P = .01). Frail infection patients had higher 30-day complication rates (14.0 versus 8.3%, P < .01). Frail instability patients had higher 30-day complication (8.0 versus 3.5%, P < .01) and reoperation rates (3.2 versus 1.6%, P < .01). CONCLUSIONS: The HFRS may identify patients at risk for adverse events and increased costs after rTKA. Further research is needed to determine causation and mitigate complications and costs.

Patient Frailty is Correlated With Increased Adverse Events and Costs After Revision Total Hip Arthroplasty.

BACKGROUND: Frailty has been associated with poor outcomes and higher costs after primary total hip arthroplasty. However, frailty has not been studied in relation to outcomes after revision total hip arthroplasty (rTHA). This study examined the relationship between the Hospital Frailty Risk Score (HFRS), postoperative outcomes, and cost profiles following rTHA. METHODS: In this retrospective cohort study, we identified patients who underwent rTHA from January 2017 to November 2019 in the Nationwide Readmission Database. The 3 most frequently reported diagnosis codes for rTHA were then selected: dislocation; mechanical loosening; and infection. We calculated the HFRS for each patient to determine frailty status. We compared 30-day readmission rate, length of stay, and hospitalization cost between frail and nonfrail patients, using multivariate logistic and negative binomial regressions to adjust for covariates. We identified 36,243 total patients who underwent rTHA. Overall, 15,448 patients had a revision for dislocation, 11,062 for mechanical loosening, and 9,733 for infection. RESULTS: Compared to nonfrail patients, frail patients had higher rates of 30-day readmission, longer length of stay, and higher hospitalization cost. Frail patients had significantly higher rates of 30-day complication and 30-day reoperation. CONCLUSIONS: Frailty, measured using HFRS, is associated with increased postoperative complications and costs after rTHA. The HFRS has the ability to efficiently identify frail patients at-risk for perioperative complications enabling care teams to better focus optimization interventions on this patient cohort.

Understanding and Promoting Preventive Health Service Use Among Black Men: Community-Driven and Informed Insights.

Black men experience high rates of adverse health that can be prevented or mitigated by the regular use of preventive health services. Efforts are urgently needed to promote this type of health service use among Black men. The U.S. Preventive Services Task Force and the Institute of Medicine indicate that such efforts must align with Black men's values, perspectives, and preferences. However, little guidance exists on how to align these efforts for Black men. The present qualitative study was developed to understand factors associated with preventive health service use among Black men and community-informed strategies to promote preventive health service use among these men. An approach rooted in community-based participatory research and ecological theory was used. A core leadership team consisting of five Black men from the area guided the project's development, implementation, and evaluation. The core leadership team conducted 22 interviews with Black men from their communities. Four themes emerged from these interviews: (1) holistic well-being challenges faced by Black men: interaction of mental, physical, and societal forces; (2) the interplay of financial, informational, and gendered barriers/facilitators to using preventative health services among Black men; (3) the importance of shared identity in peer health education about preventive health service use; and (4) the need for community-centered initiatives to improve preventive health service use among Black men that prioritize accessibility and information. Findings of the present study can be used to tailor preventive health service use efforts for Black men. Such efforts have the potential to promote health and mitigate health disparities.

Livestock health and disease economics: a scoping review of selected literature.

Animal diseases in production and subsistence environments have the potential to negatively affect consumers, producers, and economies as a whole. A growing global demand for animal sourced food requires safe and efficient production systems. Understanding the burden of animal disease and the distribution of burden throughout a value chain informs policy that promotes safe consumption and efficient markets, as well as providing more effective pathways for investment. This paper surveys existing knowledge on the burden of animal disease across economic categories of production, prevention and treatment, animal welfare, and trade and regulation. Our scoping review covers 192 papers across peer-reviewed journals and reports published by organizations. We find there exists a gap in knowledge in evaluating what the global burdens of animal diseases are and how these burdens are distributed in value chains. We also point to a need for creating an analytical framework based on established methods that guides future evaluation of animal disease burden, which will provide improved access to information on animal health impacts.

Analysis of a beta-lactam allergy assessment protocol challenging diverse reported allergies managed by an antimicrobial stewardship program.

Objective: To assess the safety and efficacy of a novel beta-lactam allergy assessment algorithm managed by an antimicrobial stewardship program (ASP) team. Design: Retrospective analysis. Setting: One quaternary referral teaching hospital and one tertiary care teaching hospital in a large western Pennsylvania health network. Patients or participants: Patients who received a beta-lactam challenge dose under the beta-lactam allergy assessment algorithm. Interventions: A beta-lactam allergy assessment protocol was designed and implemented by an ASP team. The protocol risk stratified patients' reported allergies to identify patients appropriate for a challenge with a beta-lactam antibiotic. This retrospective analysis assessed the safety and efficacy of this protocol among patients receiving a challenge dose from November 2017 to July 2021. Results: Over a 45-month period, 119 total patients with either penicillin or cephalosporin allergies entered the protocol. Following a challenge dose, 106 (89.1%) patients were treated with a beta-lactam. Eleven patients had adverse reactions to a challenge dose, one of which required escalation of care to the intensive care unit. Of the patients with an unknown or low-risk reported allergy, 7/66 (10.6%) had an observed adverse reaction compared to 3/42 (7.1%) who had an observed reaction with a reported high-risk or anaphylactic allergy. Conclusions: Our implemented protocol was safe and effective, with over 90% of patients tolerating the challenge without incident and many going on to receive indicated beta-lactam therapy. This protocol may serve as a framework for other inpatient ASP teams to implement a low-barrier allergy assessment led by ASP teams.

Research Priorities for the Environmental Risk Assessment of Per- and Polyfluorinated Substances.

Per- and polyfluorinated substances (PFAS) are a group of thousands of ubiquitously applied persistent industrial chemicals. The field of PFAS environmental research is developing rapidly, but suffers from substantial biases toward specific compounds, environmental compartments, and organisms. The aim of our study was therefore to highlight current developments and to identify knowledge gaps and subsequent research needs that would contribute to a comprehensive environmental risk assessment for PFAS. To this end, we consulted the open literature and databases and found that knowledge of the environmental fate of PFAS is based on the analysis of <1% of the compounds categorized as PFAS. Moreover, soils and suspended particulate matter remain largely understudied. The bioavailability, bioaccumulation, and food web transfer studies of PFAS also focus on a very limited number of compounds and are biased toward aquatic biota, predominantly fish, and less frequently aquatic invertebrates and macrophytes. The available ecotoxicity data revealed that only a few PFAS have been well studied for their environmental hazards, and that PFAS ecotoxicity data are also strongly biased toward aquatic organisms. Ecotoxicity studies in the terrestrial environment are needed, as well as chronic, multigenerational, and community ecotoxicity research, in light of the persistency and bioaccumulation of PFAS. Finally, we identified an urgent need to unravel the relationships among sorption, bioaccumulation, and ecotoxicity on the one hand and molecular descriptors of PFAS chemical structures and physicochemical properties on the other, to allow predictions of exposure, bioaccumulation, and toxicity. Environ Toxicol Chem 2023;42:2302-2316. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Spectrometric Assessment of Generic and Brand Drug Quality for a Sentinel Screening Network.

The U.S. Food and Drug Administration (FDA) is a worldwide leader among analogous regulatory organizations in other countries. The FDA uses current good manufacturing practices to regulate the processes that produce drugs. Nevertheless, investigative journalists have pointed out problems in the drug supply, and pharmacies are not required to test the drugs they receive. The University of Kentucky Drug Quality Study does perform screening on the sterile injectable drugs that it receives and regularly reports new findings to FDA, practitioners, and the public. A Sentinel Screening Network of academic health systems could provide independent data on drug quality to FDA not available through manufacturers.

Pumping iron: A multi-omics analysis of two extremophilic algae reveals iron economy management.

Marine algae are responsible for half of the world's primary productivity, but this critical carbon sink is often constrained by insufficient iron. One species of marine algae, Dunaliella tertiolecta, is remarkable for its ability to maintain photosynthesis and thrive in low-iron environments. A related species, Dunaliella salina Bardawil, shares this attribute but is an extremophile found in hypersaline environments. To elucidate how algae manage their iron requirements, we produced high-quality genome assemblies and transcriptomes for both species to serve as a foundation for a comparative multiomics analysis. We identified a host of iron-uptake proteins in both species, including a massive expansion of transferrins and a unique family of siderophore-iron-uptake proteins. Complementing these multiple iron-uptake routes, ferredoxin functions as a large iron reservoir that can be released by induction of flavodoxin. Proteomic analysis revealed reduced investment in the photosynthetic apparatus coupled with remodeling of antenna proteins by dramatic iron-deficiency induction of TIDI1, which is closely related but identifiably distinct from the chlorophyll binding protein, LHCA3. These combinatorial iron scavenging and sparing strategies make Dunaliella unique among photosynthetic organisms.