Threshold Analysis Research Articles

Cost-effectiveness analysis of 20-valent pneumococcal conjugate vaccine for routine pediatric vaccination programs in Japan

ABSTRACT Background The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. Methods A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. Results PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). Conclusions As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.

The Cost-Effectiveness of Computer-Assisted Compared with Conventional Total Knee Arthroplasty: A Payer's Perspective.

Recent evidence showing that computer-assisted total knee arthroplasty (TKA) is associated with better outcomes compared with conventional TKA for patients with end-stage knee osteoarthritis has not been included in economic evaluations of computer-assisted TKA, which are needed to support coverage decisions. This study evaluated the cost-effectiveness of computer-assisted TKA from a payer's perspective, incorporating recent evidence. We compared computer-assisted TKA with conventional TKA with regard to costs (in 2022 U.S. dollars) and quality-adjusted life-years (QALYs) using Markov models for elderly patients (≥65 years of age) and patients who were not elderly (55 to 64 years of age). Costs and QALYs were estimated in the lifetime for elderly patients and in the short term for patients who were not elderly, under a bundled payment program and a Fee-for-Service program. Transition probabilities, costs, and QALYs were retrieved from the literature, a national knee arthroplasty registry, and the National Center for Health Statistics. Threshold and probabilistic sensitivity analyses were conducted to examine the robustness of key estimates used in the base-case analysis. Using projected estimates of TKA utilization, the total cost savings of performing computer-assisted TKA rather than conventional TKA were estimated. Compared with conventional TKA, computer-assisted TKA was associated with higher QALYs and lower costs for both elderly patients and patients who were not elderly, regardless of payment programs, making computer-assisted TKA a favorable treatment option. Widespread adoption of computer-assisted TKA in all U.S. patients would result in an estimated total cost saving of $1 billion for payers. Compared with conventional TKA, computer-assisted TKA reduces costs to payers while providing favorable outcomes. Payers may consider providing additional payment incentives to providers for performing computer-assisted TKA, to achieve outcome improvement and cost control by facilitating widespread adoption of computer-assisted TKA. Economic and Decision Analysis Level II. See Instructions for Authors for a complete description of levels of evidence.

How does governance quality affect the shadow economy-sustainable development nexus? New insights from a dynamic threshold analysis

Purpose The purpose of this study is to assess the impact of the shadow economy on three sustainable development indicators while considering the moderating effect of the governance quality, and to highlight the non-linearity of the considered relationship.Design/methodology/approach A sample of 82 countries covering the period from 1996 to 2017. The dynamic first-differenced generalized method of moments (FD-GMM) panel threshold model is implemented to control for non-linearity.Findings The shadow economy hinders sustainable development in countries with low-governance quality, while the opposite result holds in countries with high-governance quality. The critical thresholds triggering the switch from one regime to another vary across the sustainable development indicators. Boosting growth requires enhancing the legal system and the economic dimension of governance, while promoting environmental quality requires the implementation and enforcement of specific environment-friendly regulations.Originality/value The study addresses non-linearity and the moderating effect of governance quality. The use of six governance indicators allows to gauge the ability of each governance dimension to curb the negative effects of the shadow economy. Considering the three objectives of sustainable development allows to identify specific policy recommendations for each of them.

Cost-Effectiveness Analysis of the Clear Cell Likelihood Score Against Renal Mass Biopsy for Evaluating Small Renal Masses

ObjectiveTo examine the cost-effectiveness of the clear cell likelihood score compared to renal mass biopsy alone. MethodsThe clear cell likelihood score, a new grading system based on multiparametric magnetic resonance imaging, has been proposed as a possible alternative to percutaneous renal mass biopsy for identifying clear cell renal carcinoma in small renal masses and expediting treatment of high-risk patients. A decision analysis model was developed to compare a renal mass biopsy strategy where all patients undergo biopsy and a clear cell likelihood score strategy where only patients that received an indeterminant score of 3 undergo biopsy. Effectiveness was assigned 1 for correct diagnoses and 0 for incorrect or indeterminant diagnoses. Costs were obtained from institutional fees and Medicare reimbursement rates. Probabilities were derived from literature estimates from radiologists trained in the clear cell likelihood score. ResultsIn the base case model, the clear cell likelihood score was both more effective (0.77 vs. 0.70) and less expensive than renal mass biopsy ($1629 vs. $1966). Sensitivity analysis found that the nondiagnostic rate of renal mass biopsy and the sensitivity of the clear cell likelihood score had the greatest impact on the model. In threshold analyses, the clear cell likelihood score was the preferred strategy when its sensitivity was greater than 62.7% and when an MRI cost less than $5332. ConclusionsThe clear cell likelihood score is a more cost-effective option than renal mass biopsy alone for evaluating small renal masses for clear cell renal carcinoma.

Is there an optimal level of leverage? The case of banks and non-bank institutions in Europe

In this paper, we evaluate whether banks and non-banks size and systemic risk are affected by their level of leverage. We implement a threshold analysis to a sample of European traditional banks and non-banks (Finance services and Real Estate Finance Services) over 2006:1-2019:4. We find that Finance Services show positive co-movements between leverage and size, independently of the level of leverage, while for traditional banks the level of leverage matters. Both banks and non-banks show positive correlation between leverage and systemic risk. During periods of crisis, SRISK measure of systemic risk allows to identify an optimal level of leverage.

Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss

Obesity is a disease with a large socioeconomic burden. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic bariatric procedure with wide global adoption. More recently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (eg, semaglutide), have attracted increased attention due to their efficacy. However, their cost-effectiveness over an extended period compared with ESG is a critical gap that needs to be better explored for informed health care decision-making. To assess the cost-effectiveness of semaglutide compared with ESG over 5 years for individuals with class II obesity. This economic evaluation study, conducted from September 1, 2022, to May 31, 2023, used a Markov cohort model to compare ESG and semaglutide, with a no-treatment baseline strategy. The study comprised adult patients in the US health care system with class II obesity (body mass index [BMI] of 35-39.9). The base case was a 45-year-old patient with class II obesity (BMI of 37). Patients undergoing ESG were subjected to risks of perioperative mortality and adverse events with resultant costs and decrement in quality of life. Strategies included treatment with semaglutide and ESG. Costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100 000/QALY. A 5-year time horizon with a cycle length of 1 month with a 3% discount rate was used. Probabilities, costs, and quality-of-life estimates of the model were derived from published literature. One-way, 2-way, and probabilistic sensitivity analyses were also performed. The model found that ESG was more cost-effective than semaglutide over a 5-year time horizon, with an ICER of -$595 532/QALY. Endoscopic sleeve gastroplasty added 0.06 QALYs and reduced total cost by $33 583 relative to semaglutide. The results remained robust on 1-way and probabilistic sensitivity analyses. Endoscopic sleeve gastroplasty sustained greater weight loss over 5 years vs semaglutide (BMI of 31.7 vs 33.0). To achieve nondominance, the annual price of semaglutide, currently $13 618, would need to be $3591. This study suggests that ESG is cost saving compared with semaglutide in the treatment of class II obesity. On price threshold analyses, a 3-fold decrease in the price of semaglutide is needed to achieve nondominance.

Comparative Analysis of Pooling Methods for SARS-CoV-2 Real-time Polymerase Chain Reaction Testing

Abstract Background: Wide spread coronavirus 2019 (COVID-19) infections in 2020 and 2021 and fewer real-time polymerase chain reaction (PCR) laboratories placed extraordinary demand on molecular diagnostics. To accommodate demand for increased testing volumes, the Indian Council of Medical Research had initially allowed pooling of five samples. This study aimed to conduct a comparative analysis of three sample pooling methods for SARS-CoV-2 testing to assess their effectiveness, sensitivity, and specificity. Methods: In this cross-sectional study, samples intended for SARS-CoV-2 testing were initially tested individually and then combined in a 1:4 positive-to-negative ratio. A total of 90 pools, comprising 450 samples, were analyzed using three distinct pooling methods: swab pooling, viral transport medium (VTM) pooling, and RNA pooling, all targeting the detection of the RdRp gene. PCR testing was conducted for all 90 pools comprising 450 samples in a uniform manner. Results: Swab pooling and RNA pooling methods correctly identified RdRp gene in all samples. VTM pooling method failed to identify RdRp gene in 4 samples. Analysis of cycle threshold (CT) value showed, loss of mean CT value of 2.80 ± 0.86 in swab pooling method with Z score of 6.03, VTM pooling method showed loss of mean CT value of 1.96 ± 0.76 with Z score of 3.22 and RNA pooling method showed loss of mean CT value of 1.73 ± 0.58 with Z score of 4.29 in. P value was statistically significant (<0.001) in all three methods. Conclusion: This study concludes that the RNA pooling method is superior, with minimal sensitivity loss in CT values. Swab pooling is cost-effective for negative pools but impractical for positive ones, while the VTM pooling method offers greater cost-effectiveness compared to RNA pooling.

Foreign Direct Investment and Industry Value-Added in Egypt: Economic Complexity Threshold Analysis

Foreign Direct Investment and Industry Value-Added in Egypt: Economic Complexity Threshold Analysis

Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location

BackgroundPersistent pregnancies of unknown location (PUL) are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. ObjectiveThis study was designed to assess the cost-effectiveness between three primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical two-dose methotrexate, (3) uterine evacuation followed by methotrexate, if indicated. Study DesignWe conducted a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location (ACT or NOT) multicenter randomized trial conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, two-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon following randomization. Costs were expressed in 2018 U.S. dollars. Effectiveness was measured in quality-adjusted life-years (QALYs) and the rate of salpingectomy. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. ResultsMethotrexate had the lowest mean cost, $875, followed by expectant management $1085, and uterine evacuation $1902 (p=0.001). Expectant management had the highest mean QALY (0.1043) followed by methotrexate (0.1031) and uterine evacuation (0.0992) (p=0.0001). Salpingectomy rate was higher for expectant management compared to methotrexate (9.4% vs 1.2%; p=0.02) and expectant management compared to uterine evacuation (9.4% vs 8.1%; p=0.04). Uterine evacuation, with highest costs and lowest QALYs, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY given an ICER of $175,083/QALY gained (95% CI, -$1,666,825-2,676,375). Threshold analysis demonstrated methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Expectant management would also be favorable in lower risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability expectant management was cost-effective compared to methotrexate at a willingness-to-pay of $150,000/QALY gained was 50%. Results were dependent on the cost of surgical intervention, and the expected rate of methotrexate failure. ConclusionManagement of pregnancies of unknown location with a two-dose methotrexate protocol may be cost-effective compared to expectant management and uterine evacuation. While uterine evacuation was dominated, expectant management versus methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

Revisiting investment and its determinants through threshold analysis

AbstractSince the time of classical economists, investment decisions hold centre stage in economic theory. In this article, we integrate classical economists' perspectives on the determinants of investment with the Keynesian theory of effective demand. For this purpose, we employ variables to capture the effects of profitability, the state of demand, and the financial and risk conditions using time series data from 17 major OECD economies spanning the 1960–2017 period. Two are the salient features of our article: The first is the use as profitability variables, the marginal efficiency of capital or the incremental rate of return, and the second is the use of regime changes and respective threshold values for these two key variables. The econometric results show that the profitability variables are decisive in shaping investment decisions and designating phase changes.

Impact of marine industrial agglomeration on high-quality marine economic development: the mediating effect of knowledge spillover

Industrial agglomeration significantly influences economic development; however, its impact on high-quality economic growth within the marine industry remains understudied. We conducted a study using panel data from 11 coastal provinces in China (2008–2020) and used the entropy method to quantify high-quality marine economic development (HQMED). Our study meticulously examines the direct, mediating, and nonlinear effects of marine industrial agglomeration (MIA) on HQMED. The key findings include the following: (1) There is a steady HQMED growth and reduced interprovincial gaps. (2) MIA significantly enhances local HQMED and leads to positive spatial spillover to adjacent regions. (3) The analysis of the mediating effect highlights the pivotal role of knowledge spillover in MIA’s influence on HQMED. (4) Threshold analysis shows significant MIA effects on local and neighboring HQMED using knowledge spillover as a threshold variable. The study’s findings hold theoretical and practical significance and guide MIA’s role in fostering sustainable marine economic development in China.

The Ratio of Serum Urea Nitrogen to Albumin Is a Better Predictor of Overall Survival in Multiple Myeloma Patients than Urea Nitrogen Alone

Introduction: Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients’ prognoses remains unknown. Therefore, we analyzed MM patients’ clinical data to explore the role of sUN and sUN/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods: We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane’s T2 test, multivariate-adjusted Cox regression analysis, Kaplan-Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results: There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with β2-microglobulin (β2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with overall survival (OS), although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate-adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. β2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost β2-MG and LDH’s predictive value and sUAR had a higher predictive value. Conclusion: This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with β2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.

Is it beneficial to invest in flexible capacity for hybrid remanufacturing?

Firms that aim to close the loop via remanufacturing returned products face uncertainties on both the demand and supply side. Inspired by industrial circular business models, we study the capacity investment problem of a manufacturer. The manufacturer can invest in a flexible (shared) resource to share capacity across processes and/or less costly dedicated manufacturing and remanufacturing resources. We model the capacity investment problem as a two-stage stochastic programme and provide structural results. Our analysis shows how the optimal resource selection depends on margin (price) and cost differentials and highlights the focal role of capacity coefficients. We identify conditions under which an investment in flexibility is beneficial even if remanufacturing is a lower-margin process. Moreover, an investment in flexible capacity can be optimal if demand and returns are perfectly positively correlated, and thus, return risk is eliminated. Contrary to intuition, optimal profits may decrease in demand-return correlation if the optimal investment includes a flexible resource. The analysis of investment thresholds shows two benefits of resource flexibility: (a) mitigation of demand and return mismatches and (b) an ex-post revenue maximisation option to allocate capacity to the more profitable process.

Repackaging FDI for inclusive growth: Nullifying effects and policy-relevant thresholds of governance

This study examines whether foreign direct investment (FDI) to SSA contributes to inclusive growth in the region. The study further investigates whether SSA's institutional fabric moderates the effect of FDI on inclusive growth in SSA. To this end, we draw data on 42 SSA countries for the period 1996–2020 for the analysis. The empirical evidence, which is based on the GMM estimator, shows that: (1) FDI impedes inclusive growth in SSA, and (2) the region's weak institutional fabric amplifies the shared growth-deteriorating effect of FDI. Nonetheless, the optimism, which we provide by way of threshold analysis, shows that efforts aimed at improving regulatory efficiency enhance inclusive growth from the short-term through to the long-term. The study concludes that robust structures for regulatory efficiency and corruption control are critical for moderating FDI to promote inclusive growth in SSA. A few policy recommendations are discussed in the end.

What is a ‘good enough’ prison? An empirical analysis of key thresholds using prison moral quality data

What is a ‘good enough’ prison? An empirical analysis of key thresholds using prison moral quality data

Accelerometer-measured physical activity and sedentary behaviour are associated with C-reactive protein in US adults who get insufficient sleep: A threshold and isotemporal substitution effect analysis

ABSTRACT This study aimed to investigate the association between physical activity, sedentary behaviour and chronic inflammation in short sleep adults. The study included 2,113 NHANES participants with self-reported insufficient sleep. C-reactive protein (CRP) was used as the inflammatory biomarker. Physical activity and sedentary behaviour were objectively measured by accelerometers. Weighted regression model, two – piecewise linear regression model, and restricted cubic splines were applied to evaluate associations mentioned above. An isotemporal substitution model was used to assess the modelled effects of replacing sedentary time (ST) with moderate-to-vigorous levels of physical activity (MVPA) or light physical activity (LPA). After adjusting for potential confounding factors, higher levels of ST and lower levels of LPA or MVPA were associated with higher CRP levels. Isotemporal substitution analysis indicated that replacing 30 minutes of ST with 30 minutes of MVPA was associated with a significant decrease in CRP levels. Saturation analysis suggested that the association between MVPA and CRP may plateau at over 20 minutes of MVPA per day. Findings of this study provides insight into the potential benefits of replacing ST with MVPA. This study also suggests that increasing MVPA beyond a certain point may not provide additional anti-inflammatory benefits in a short sleep population.

Cost-effectiveness of one-year adjuvant trastuzumab therapy in treatment for early-stage breast cancer patients with HER2+ in Vietnam.

In Vietnam, trastuzumab is included in social health insurance's benefits package with a reimbursement rate of 60%, but policymakers have been concerned about its cost-effectiveness. The research aims to evaluate the cost-effectiveness of one-year adjuvant trastuzumab therapy for early-stage breast cancer patients with human epidermal growth receptor 2 (HER2+) from a societal perspective. A Markov model was developed and validated to estimate the lifetime cost and effectiveness (using life year and quality-adjusted life year) of one-year adjuvant trastuzumab therapy compared to chemotherapy (using paclitaxel) alone. Treatment efficacy and transition probabilities were estimated based on published trials (i.e., N9831, NSABP B-31, HERA, and BCIRG 006). Local cost and utility data were employed to capture the Vietnam context. One-way sensitivity analysis, probabilistic sensitivity analysis, threshold, and scenario analysis were also performed. One-year adjuvant trastuzumab therapy combined with chemotherapy compared to chemotherapy alone yielded an additional cost of 888,453,971VND (39,062 US$) with an additional 3.09 LYs and 1.61 QALYs, resulting in an ICER of 287,390,682 VND (12,635 US$) per LY gained, or 519,616,972 VND (22,845 US$) per QALY gained. The ICER exceeds the cost-effective threshold of 1- and 3-time GDP per capita by 6.3 and 2.1 times. The probabilistic sensitivity analysis shows similar results. According to one-way sensitivity analysis, ICERs were driven mainly by transition probabilities and trastuzumab price. One-year adjuvant trastuzumab therapy would be cost-effective at the 3-time GDP per capita threshold if the cost of Herceptin 150mg and 450mg vials were reduced by 56% and 54%, correspondingly. In Vietnam, one-year adjuvant trastuzumab therapy for early-stage breast cancer with HER2+ is not cost-effective. The research provided reliable and updated evidence to support policymakers in revising the health insurance benefit package. The policymakers should consider the options to reduce the cost of trastuzumab (e.g., regarding the use of trastuzumab biosimilars, price negotiation options, and options of optimizing the use of Herceptin vials among concurrent hospitalized breast cancer patients).

The relationship between duration of infertility and clinical outcomes of intrauterine insemination for younger women: a retrospective clinical study

BackgroundThe objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus.MethodsA retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation.ResultsWhen the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043).ConclusionsThe clinical pregnancy rate and live birth rate of IUI in young women (< 35 years old) who have been infertile for more than 5 years significantly decrease with the prolongation of infertility time. Therefore, for young women who have been infertile for more than 5 years, IUI may not be the best choice.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Highest 3-month international normalized ratio (INR): a predictor of bleeding following ultrasound-guided liver biopsy.

To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy. A total of 870 consecutive patients (age 53 ± 14years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability. Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding. The highest INR in 3months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification. Despite correction of coagulopathic indices, the highest international normalized ratio within the 3months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach. • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components.