Detecting Unique Analyte-Specific Radio Frequency Spectral Responses in Liquid Solutions-Implications for Non-Invasive Physiologic Monitoring.

With rising healthcare costs and the rapid increase in remote physiologic monitoring and care delivery, there is an increasing need for economical, accurate, and non-invasive continuous measures of blood analytes. Based on radio frequency identification (RFID), a novel electromagnetic technology (the Bio-RFID sensor) was developed to non-invasively penetrate inanimate surfaces, capture data from individual radio frequencies, and convert those data into physiologically meaningful information and insights. Here, we describe groundbreaking proof-of-principle studies using Bio-RFID to accurately measure various concentrations of analytes in deionized water. In particular, we tested the hypothesis that the Bio-RFID sensor is able to precisely and non-invasively measure and identify a variety of analytes in vitro. For this assessment, varying solutions of (1) water in isopropyl alcohol; (2) salt in water, and (3) commercial bleach in water were tested, using a randomized double-blind trial design, as proxies for biochemical solutions in general. The Bio-RFID technology was able to detect concentrations of 2000 parts per million (ppm), with evidence suggesting the ability to detect considerably smaller concentration differences.

Right ventricular functional recovery assessment with stress echocardiography and cardiopulmonary exercise testing after pulmonary embolism: a pilot prospective multicentre study.

BACKGROUND: Data on right ventricular (RV) exercise adaptation following acute intermediate and high-risk pulmonary embolism (PE) remain limited. This study aimed to evaluate the symptom burden, RV functional recovery during exercise and cardiopulmonary exercise parameters in survivors of intermediate and high-risk acute PE. METHODS: We prospectively recruited patients following acute intermediate and high-risk PE at four sites in Australia and UK. Study assessments included stress echocardiography, cardiopulmonary exercise testing (CPET) and ventilation-perfusion (VQ) scan at 3 months follow-up. RESULTS: Thirty patients were recruited and 24 (median age: 55 years, IQR: 22) completed follow-up. Reduced peak oxygen consumption (VO2) and workload was seen in 75.0% (n=18), with a persistent high symptom burden (mean PEmb-QoL Questionnaire 48.4±21.5 and emPHasis-10 score 22.4±8.8) reported at follow-up. All had improvement in RV-focused resting echocardiographic parameters. RV systolic dysfunction and RV to pulmonary artery (PA) uncoupling assessed by stress echocardiography was seen in 29.2% (n=7) patients and associated with increased ventilatory inefficiency (V̇E/V̇CO2 slope 47.6 vs 32.4, p=0.03), peak exercise oxygen desaturation (93.2% vs 98.4%, p=0.01) and reduced peak oxygen pulse (p=0.036) compared with controls. Five out of seven patients with RV-PA uncoupling demonstrated persistent bilateral perfusion defects on VQ scintigraphy consistent with chronic thromboembolic pulmonary vascular disease. CONCLUSION: In our cohort, impaired RV adaptation on exercise was seen in almost one-third of patients. Combined stress echocardiography and CPET may enable more accurate phenotyping of patients with persistent symptoms following acute PE to allow timely detection of long-term complications.

A geometric assessment method for estimating dimensional change of retrieved dual mobility liners for total hip arthroplasty.

Despite their emerging use, the current understanding of the in-vivo functional mechanisms of Dual Mobility (DM) Total Hip Replacements (THRs) is poor, and current characterisation methodologies are not suitable for the unique function and design of these types of devices. Therefore, the aim of this study was to develop a geometric characterisation methodology to estimate dimensional change across the articulating surfaces of retrieved DM polyethylene liners so that their invivo function may be better understood. The method involves the acquisition of three-dimensional coordinate data from the internal and external surfaces of DM liners. The data is processed using a bespoke MATLAB script which approximates the unworn reference geometry of each surface, calculates geometric variance at each point and produces surface deviation heatmaps so that areas of wear and/or deformation may be visualised across the implant. One as-manufactured and five retrieved DM liners were assessed, which demonstrated the efficacy, repeatability and sensitivity of the developed method. This study describes an automated and non-destructive approach for assessing retrieved DM liners of any size and from any manufacturer, which may be used in future research to improve our understanding of their in-vivo function and failure mechanisms.

Racism: Eroding the health of Black communities.

ABSTRACT: Even in the context of major advances in medicine, racial minorities continue to suffer worse medical outcomes. Although race is defined as a social, nonscientific construct, researchers have continued to use it as proxy to explain genetic and evolutionary differences among patients. Poorer health outcomes among Black Americans are known to be related to the psychosocial and physiological stress of racism. Black communities experience premature health deterioration because of the cumulative effects of social, economic, and political oppression and marginalization. Additionally, recent assertions that racism is best seen as a chronic disease has added value to understanding the effect of racism on the health of Black people. Using evidence-based information to assess the health of Black patients is a key step to assist clinicians in promptly addressing this chronic threat to the health of Black patients.

Rapid Genetic Testing in Pediatric and Neonatal Critical Care: A Scoping Review of Emerging Ethical Issues.

BACKGROUND: Rapid genome-wide sequencing (rGWS) is being increasingly used to aid in prognostication and decision-making for critically ill newborns and children. Although its feasibility in this fast-paced setting has been described, this new paradigm of inpatient genetic care raises new ethical challenges. OBJECTIVE: A scoping review was performed to (1) identify salient ethical issues in this area of practice; and (2) bring attention to gaps and ethical tensions that warrant more deliberate exploration. METHODS: Data sources, Ovid Medline and Cochrane Central Register of Controlled Trials, were searched up to November 2021. Articles included were those in English relating to rGWS deployed rapidly in a critical care setting. Publications were examined for ethical themes and were further characterized as including a superficial or in-depth discussion of that theme. New themes were inductively identified as they emerged. RESULTS: Ninety-nine studies, published in 2012 or thereafter, met inclusion criteria. Themes identified elaborated upon established ethical principles related to beneficence and nonmaleficence (ie, clinical utility, medical uncertainty, impact on family, and data security) autonomy (ie, informed consent), and justice (ie, resource allocation and disability rights). Many themes were only narrowly discussed. CONCLUSIONS: The application of rGWS in neonatal and pediatric acute care is inherently tied to ethically charged issues, some of which are reported here. Attention to the ethical costs and benefits of rGWS is not always discussed, with important gaps and unanswered questions that call for ongoing focus on these ethical considerations in this next application of acute care genomics.

Racial and ethnic disparities in outcomes through 1 year of life in infants born prematurely: a population based study in California.

OBJECTIVES: To investigate racial/ethnic differences in rehospitalization and mortality rates among premature infants over the first year of life. STUDY DESIGN: A retrospective cohort study of infants born in California from 2011 to 2017 (n = 3,448,707) abstracted from a California Office of Statewide Health Planning and Development database. Unadjusted Kaplan-Meier tables and logistic regression controlling for health and sociodemographic characteristics were used to predict outcomes by race/ethnicity. RESULTS: Compared to White infants, Hispanic and Black early preterm infants were more likely to be readmitted; Black late/moderate preterm (LMPT) infants were more likely to be readmitted and to die after discharge; Hispanic and Black early preterm infants with BPD were more likely to be readmitted; Black LMPT infants with RDS were more likely to be readmitted and die after discharge. CONCLUSIONS: Racial/ethnic disparities in readmission and mortality rates exist for premature infants across several co-morbidities. Future studies are needed to improve equitability of outcomes.

The economics of shrimp disease.

Shrimp is not only one of the world's most valuable aquaculture species, but also a species that encounter high economic losses due to diseases. Diseases are sufficiently important to influence global supply and prices for longer periods. Profitability is the driving force behind shrimp farming and high profits associated with the absence of disease largely determines where shrimp production does take place; i.e. prevalence of disease leads to geographic relocation. In this paper, a basic economic model for the impact of the disease on a shrimp farm is provided and a Monte Carlo simulation is provided to illustrate the impact of disease on economic risk. Improved technologies, knowledge, and governance are important elements utilized in the mitigation of diseases in various shrimp producing countries. Economic aspects such as profitability in the absence and presence of diseases and cost of treatment determines the global production of shrimp along with shaping technologies and production systems.

Patient safety and quality improvement: Ethical principles for a regulatory approach to bias in healthcare machine learning.

Accumulating evidence demonstrates the impact of bias that reflects social inequality on the performance of machine learning (ML) models in health care. Given their intended placement within healthcare decision making more broadly, ML tools require attention to adequately quantify the impact of bias and reduce its potential to exacerbate inequalities. We suggest that taking a patient safety and quality improvement approach to bias can support the quantification of bias-related effects on ML. Drawing from the ethical principles underpinning these approaches, we argue that patient safety and quality improvement lenses support the quantification of relevant performance metrics, in order to minimize harm while promoting accountability, justice, and transparency. We identify specific methods for operationalizing these principles with the goal of attending to bias to support better decision making in light of controllable and uncontrollable factors.

Assessment of Clinical Activity of PD-1 Checkpoint Inhibitor Combination Therapies Reported in Clinical Trials.

Importance: Because cancer drugs given in combination have the potential for increased tumor-cell killing, finding the best combination partners for programmed cell death 1 (PD-1) checkpoint inhibitors could improve clinical outcomes for patients with cancer. Objective: To identify optimal strategies for combining PD-1 immune checkpoint inhibitors with other cancer therapies. Design, Setting, and Participants: This cross-sectional study compiled 319 results from 98 clinical trials testing PD-1 pathway inhibitors alone or in combination with other agents among 24 915 patients with metastatic cancer. All clinical trials had a primary completion date before September 16, 2018. Data analysis was conducted from November 2018 to August 2019. Exposures: Patients with metastatic cancer were treated with PD-1 immune checkpoint inhibitors alone or with other cancer therapies. Main Outcomes and Measures: Clinical activity was measured as objective response rates (ORRs). Combination measures included fold change from monotherapy to combination ORR, comparison of observed combination ORRs with estimated combination ORRs based on independent additivity, and a computational model to assess clinical synergy. To assess whether the ORRs of various combinations may be greater than the independent contribution of each agent, a Bliss independent activity model was used to analyze observed combination ORRs, and a Z score, measuring the difference between observed and calculated ORRs, was generated. Results: In 319 results from 98 clinical trials among 24 915 patients, ORRs for monotherapy were compared with combination data by indication and line of therapy, demonstrating an increased ORR in 105 of 127 results (82.7%) where ORRs were available for both PD-1 pathway inhibitor monotherapy and combination therapy. A few combinations showed increases above the Bliss-estimated activity, possibly identifying limited clinical synergy. The mean (SD) Z score for all trials was 0.0430 (0.0243). The mean (SD) Z score was 0.0923 (0.0628) for platinum chemotherapy regimen combinations, 0.0547 (0.0821) for vascular endothelial growth factor or vascular endothelial growth factor receptor tyrosine kinase inhibitor combinations, 0.0893 (0.086) for indoleamine 2,3-dioxygenase inhibitor combinations, and 0.0558 (0.0849) for cytotoxic T-lymphocyte-associated protein 4 inhibitor combinations. Conclusions and Relevance: In this cross-sectional study, most combination trials showed the expected benefit of combining 2 active anticancer agents, but few combination trials showed clinical synergy according to the Bliss independent activity model.

The NIH Common Fund/Roadmap Epigenomics Program: Successes of a comprehensive consortium.

The NIH Roadmap Epigenomics Program was launched to deliver reference epigenomic data from human tissues and cells, develop tools and methods for analyzing the epigenome, discover novel epigenetic marks, develop methods to manipulate the epigenome, and determine epigenetic contributions to diverse human diseases. Here, we comment on the outcomes from this program: the scientific contributions made possible by a consortium approach and the challenges, benefits, and lessons learned from this group science effort.

The fishery performance indicators for global tuna fisheries.

We characterize the ecological, economic, and community performance of 21 major tuna fisheries, accounting for at least 77% of global tuna production, using the Fishery Performance Indicators. Our analysis reveals that the biggest variations in performance among tuna fisheries are driven by the final markets that they target: international sashimi market tuna fisheries considerably outperform a comparison set of 62 non-tuna fisheries in the Fishery Performance Indicator database, international canned tuna market fisheries perform similarly to the comparison set, and tuna fisheries supplying local markets in coastal states considerably underperform the comparison set. Differences among regional fishery management organizations primarily reflect regional species composition and market access, despite stark variation in governance, management, and other enabling conditions. With a legacy of open access, tuna's harvest sector performance is similar across all fisheries, reflecting only a normal return on the capital and skill invested: industrial vessels slightly outperform semi-industrial and artisanal vessels. Differences emerge in the post-harvest sector however, as value chains able to preserve quality and transport fish to high value markets outperform others.

Burden and emergency department management of acute cough in children.

AIM: In children presenting to an emergency department (ED) with an acute coughing illness, the aims of this study were to: (i) describe the frequency of doctor visits and medication use; and (ii) describe management and relate it to current evidence-based guidelines. METHODS: This was a cross-sectional study in ED of a major teaching hospital (Royal Children's Hospital, Brisbane, Australia). Participants included 537 children (<15 years) presenting with acute (<2 weeks) cough, with a median age of 2.2 years (interquartile range 1.0-4.0); 61.5% were boys. Hospitalised children and those with asthma, pneumonia or chronic illnesses were excluded. Main outcome measures were: (i) frequency of pre-ED doctor visits and medication use; and (ii) comparison of management to current evidence-based recommendations related to four discharge diagnoses: bronchiolitis, 'wheeze/reactive airway disease (RAD)', croup and 'non-specific acute respiratory illness'. RESULTS: A total of 300 children (55.9%) had seen a doctor prior to their ED presentation, and use of medications pre-ED was high (53.4%). While 93.4% of children with croup were treated in accordance with guidelines, concordance was lower for children with bronchiolitis or 'wheeze/RAD'. The majority of children with a discharge diagnosis of 'wheeze/RAD' (95.6%) received bronchodilators, and 72.7% also received oral corticosteroids but were not diagnosed with asthma. More than half (55.1%) of the children with non-specific acute respiratory illness received medication(s) either prior to or during their ED presentation. CONCLUSIONS: The burden of acute cough-related illnesses in children is high, and there is a need for improved uptake of evidence-based guidelines. In addition, the large number of children diagnosed with 'wheeze/RAD' suggests asthma is likely under-diagnosed in this setting.

Are fishery management upgrades worth the cost?

Many analyses of fishery recovery have demonstrated the potential biological and economic benefits of management reform, but few have compared these to the associated costs of management upgrades, which can be substantial. This study aims to determine if the projected economic benefits of management reform outweigh the increases in management costs required to achieve those benefits. To answer this question, we developed a database of country-level fisheries management costs and use those to estimate the country-level costs of management changes. We use this framework to compare estimates of future costs of management upgrades against their economic benefits in terms of profit. Results indicate that for most nations, including the top 25 fishing nations, management upgrades outweigh their associated costs. This result is robust to a number of alternative assumptions about costs. Results also suggest that stronger reforms such as rights-based management, although sometimes more expensive to implement, can lead to greater net economic benefits compared to alternatives.

Three pillars of sustainability in fisheries.

Sustainability of global fisheries is a growing concern. The United Nations has identified three pillars of sustainability: economic development, social development, and environmental protection. The fisheries literature suggests that there are two key trade-offs among these pillars of sustainability. First, poor ecological health of a fishery reduces economic profits for fishers, and second, economic profitability of individual fishers undermines the social objectives of fishing communities. Although recent research has shown that management can reconcile ecological and economic objectives, there are lingering concerns about achieving positive social outcomes. We examined trade-offs among the three pillars of sustainability by analyzing the Fishery Performance Indicators, a unique dataset that scores 121 distinct fishery systems worldwide on 68 metrics categorized by social, economic, or ecological outcomes. For each of the 121 fishery systems, we averaged the outcome measures to create overall scores for economic, ecological, and social performance. We analyzed the scores and found that they were positively associated in the full sample. We divided the data into subsamples that correspond to fisheries management systems with three categories of access-open access, access rights, and harvest rights-and performed a similar analysis. Our results show that economic, social, and ecological objectives are at worst independent and are mutually reinforcing in both types of managed fisheries. The implication is that rights-based management systems should not be rejected on the basis of potentially negative social outcomes; instead, social considerations should be addressed in the design of these systems.

Radiology Residency Match: The Cost of Being in the Dark.

RATIONALE AND OBJECTIVES: The Electronic Resident Application Service (ERAS) publishes monthly statistics before the match and the National Resident Matching Program publishes the match outcomes. We sought to determine whether early ERAS data influences applicant behavior and correlates with match outcomes. MATERIALS AND METHODS: We searched the 2007-2017 ERAS archives for the applicant pool size (PS), the average number of applications per program (AP), and the average number of applications per applicant (AA) in November, before radiology match, and the 2007-2017 National Resident Matching Program archives for the average number of ranked applicants needed to fill each position (ANRA) and the number of unfilled positions (UP) in radiology match. Correlation coefficients were calculated for each pair. RESULTS: PS correlated very strongly with AP (r = 0.80, p = 0.001708), UP (r = -0.92, p = 0.000063) and ANRA (r = -0.90, p = 0.000164). UP correlated strongly with ANRA (r = 0.76, p = 0.006349) and AP (r = -0.77, p = 0.005339). A trend to moderate correlation between AP and ANRA (r = 0.58, p = 0.062686) and AA (r = 0.53, p = 0.074395) did not reach statistical significance. There was no correlation between AA and PS in the same (r = -0.05, p = 0.878585) or the following year (r = 0.35, p = 0.297166), and AA and UP in the same (r = 0.13, p = 0.701983) or the following year (r = 0.32, p = 0.336136). CONCLUSION: The real-time data reported by ERAS in November, before match, is a predictor of radiology match outcomes and can be used by all participants to limit their application and recruitment costs. Medical students applying to radiology do not consider either the real-time or historic data when submitting ERAS applications.

Development of Glatopa® (Glatiramer Acetate): The First FDA-Approved Generic Disease-Modifying Therapy for Relapsing Forms of Multiple Sclerosis.

The multiple sclerosis (MS) treatment landscape in the United States has changed dramatically over the past decade. While many disease-modifying therapies (DMTs) have been approved by the US Food and Drug Administration (FDA) for the treatment of relapsing forms of MS, DMT costs continue to rise. The availability of generics and biosimilars in the MS-treatment landscape is unlikely to have a major impact on clinical benefit. However, their availability will provide alternative treatment options and potentially lower costs through competition, thus increasing the affordability of and access to these drugs. In April 2015, the first generic version of the complex drug glatiramer acetate (Glatopa® 20 mg/mL) injection was approved in the United States as a fully substitutable generic for all approved indications of the 20 mg/mL branded glatiramer acetate (Copaxone®) dosage form. Despite glatiramer acetate's complex nature-being a chemically synthesized (ie, nonbiologic) mixture of peptides-the approval occurred without conducting any clinical trials. Rather, extensive structural and functional characterization was performed to demonstrate therapeutic equivalence to the innovator drug. The approval of Glatopa signifies an important milestone in the US MS-treatment landscape, with the hope that the introduction of generic DMTs and eventually biosimilar DMTs will lead to future improvements in the affordability and access of these much-needed treatments for MS.

Racial and Ethnic Disparities in Preterm Infant Mortality and Severe Morbidity: A Population-Based Study.

BACKGROUND: Disparities exist in the rates of preterm birth and infant mortality across different racial/ethnic groups. However, only a few studies have examined the impact of race/ethnicity on the outcomes of premature infants. OBJECTIVE: To report the rates of mortality and severe neonatal morbidity among multiple gestational age (GA) groups stratified by race/ethnicity. METHODS: A retrospective cohort study utilizing linked birth certificate, hospital discharge, readmission, and death records up to 1 year of life. Live-born infants ≤36 weeks born in the period 2007-2012 were included. Maternal self-identified race/ethnicity, as recorded on the birth certificate, was used. ICD-9 diagnostic and procedure codes captured neonatal morbidities (intraventricular hemorrhage, retinopathy of prematurity, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis). Multiple logistic regression was performed to evaluate the impact of race/ethnicity on mortality and morbidity, adjusting for GA, birth weight, sex, and multiple gestation. RESULTS: Our cohort totaled 245,242 preterm infants; 26% were white, 46% Hispanic, 8% black, and 12% Asian. At 22-25 weeks, black infants were less likely to die than white infants (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.62-0.94). However, black infants born at 32-34 weeks (OR 1.64; 95% CI 1.15-2.32) or 35-36 weeks (OR 1.57; 95% CI 1.00-2.24) were more likely to die. Hispanic infants born at 35-36 weeks were less likely to die than white infants (OR 0.66; 95% CI 0.50-0.87). Racial disparities at different GAs were also detected for severe morbidities. CONCLUSIONS: The impact of race/ethnicity on mortality and severe morbidity varied across GA categories in preterm infants. Disparities persisted even after adjusting for important potential confounders.