Inpatient Costs of Treating Patients With COVID-19.

Importance: With more than 6.2 million hospitalizations due to COVID-19 in the US, recognition of the average hospital costs to provide inpatient care during the pandemic is necessary to understanding the national medical resource use and improving public health readiness and related policies. Objective: To examine the mean cost to provide inpatient care to treat COVID-19 and how it varied through the pandemic waves and by important sociodemographic patient characteristics. Design, Setting, and Participants: This cross-sectional study used inpatient-level data from March 1, 2020, to March 31, 2022, extracted from a repository of clinical, administrative, and financial information covering 97% of academic medical centers across the US. Main Outcomes and Measures: Cost to produce care for each stay was calculated using direct hospital costs to provide care adjusted for geographic differences in labor costs using area wage indices. Results: The sample included 1 333 404 stays with a primary or secondary COVID-19 diagnosis from 841 hospitals. The cohort included 692 550 (52%) men, with mean (SD) age of 59.2 (17.5) years. The adjusted mean cost of an inpatient stay was $11 275 (95% CI, $11 252-$11 297) overall, increasing from $10 394 (95% CI, $10 228-$10 559) at the end of March 2020 to $13 072 (95% CI, $12 528-$13 617) by the end of March 2022. Patients with specific comorbidities had significantly higher mean costs than their counterparts: those with obesity incurred an additional $2924 in inpatient stay costs, and those with coagulation deficiency incurred an additional $3017 in inpatient stay costs. Stays during which the patient required extracorporeal membrane oxygenation (ECMO) had an adjusted mean cost of $36 484 (95% CI, $34 685-$38 284). Conclusions and Relevance: In this cross-sectional study, an adjusted mean hospital cost to provide care for patients with COVID-19 increased more than 5 times the rate of medical inflation overall. This appeared to be explained partly by changes in the use of ECMO, which increased over time.

Determination of the polyphenolic content of berry juices using focusing-modulated comprehensive two-dimensional liquid chromatography coupled to mass spectrometry detection.

In this work, a comprehensive two-dimensional liquid chromatography system, comprised of a ZIC-HILIC and C18 columns in the first and second dimensions, respectively, was tuned and employed for attaining high resolution profiles of the polyphenolic pattern in seven commercial berry juices. The developed HILIC × RP-LC method was validated in terms of linearity range, correlation coefficients, limit of detection, limit of quantification, precision (intra- and inter-day), and recovery. A total of 104 polyphenolic compounds belonging to different chemical classes (hydroxybenzoic and cinnamic acid derivatives, flavone glycosides, flavonols, flavonol glycosides, dihydroflavonols, and anthocyanin glycosides) have been characterized and quantified in the juices investigated. Despite the constituents being similar, a notable quantitative variation among the analyzed berry species was observed. Elderberry contained the highest amount of polyphenols (918 ± 1.10 mg 100 mL-1), followed by chokeberry (516 ± 0.08 mg 100 mL-1). On the other hand, raspberry contained the lowest amount (104 ± 1.21 mg 100 mL-1). Further, total phenolic, flavonoid, and anthocyanin contents were determined spectrophotometrically, yielding consistent results. The free-radical scavenging activity (DPPH test) and reducing power of the juices, expressed as IC50 (µL mL-1) and mg ASE mL-1, varied from 2.79 ± 0.03 (honeyberry) to 31.66 ± 0.02 (blueberry) and from 1.71 ± 0.01 (blueberry) to 8.89 ± 0.12 (chokeberry), respectively. Such a ZIC-HILIC × C18 platform based on focusing modulation, never employed so far for berry juices, showed a remarkable separation capability with high values of corrected peak capacity (up to 1372) and orthogonality (Ao up to 0.80), thus providing a great applicability to be advantageously employed for other complex food samples.

Surge in Incidence and Coronavirus Disease 2019 Hospital Risk of Death, United States, September 2020 to March 2021.

Background: Studies of the early months of the coronavirus disease 2019 (COVID-19) pandemic indicate that patient outcomes may be adversely affected by surges. However, the impact on in-hospital mortality during the largest surge to date, September 2020-March 2021, has not been studied. This study aimed to determine whether in-hospital mortality was impacted by the community surge of COVID-19. Methods: This is a retrospective cohort study of 416 962 adult COVID-19 patients admitted immediately before or during the surge at 229 US academic and 432 community hospitals in the Vizient Clinical Database. The odds ratios (ORs) of death among hospitalized patients during each phase of the surge was compared with the corresponding odds before the surge and adjusted for demographic, comorbidity, hospital characteristic, length of stay, and complication variables. Results: The unadjusted proportion of deaths among discharged patients was 9% in both the presurge and rising surge stages but rose to 12% during both the peak and declining surge intervals. With the presurge phase defined as the referent, the risk-adjusted ORs (aORs) for the surge periods were rising, 1.14 (1.10-1.19), peak 1.37 (1.32-1.43), and declining, 1.30 (1.25-1.35). The surge rise in-hospital mortality was present in 7 of 9 geographic divisions and greater for community hospitals than for academic centers. Conclusions: These data support public policies aimed at containing pandemic surges and supporting healthcare delivery during surges.

A Structural, Cognitive, and Behavioral Model for Error Analysis of Group B Streptococcus Prophylaxis in Pregnancy.

The objective of this study was to develop a structural-cognitive-behavioral model for error analysis of group B streptococcus (GBS) prophylaxis failure, classify delivery cases into this model, and examine compliance with treatment guidelines. A retrospective, cohort study was conducted of women with liveborn pregnancies greater than 24 weeks in April 2018 at a single hospital. We created a structural-cognitive-behavioral model of five assessments for adherence to GBS prophylaxis guidelines and then classified these into four distinct error stages. A descriptive analysis was performed to determine if the pregnancy had a perfect process, a GBS prophylaxis failure, or a fortuitous outcome. There were 313 women who met the study criteria. The rate of GBS positive was 12.8%, negative 37.4%, and unknown 49.8%. The most common errors were cognitive perception errors related to incorrectly documenting GBS status, 57.7% ( N = 79). Of these errors, 15.2% ( N = 12) led to GBS prophylaxis failure. Perfect outcomes occurred in 62.7% ( N = 196) women, GBS prophylaxis failure occurred in 13.7% ( N = 43), and fortuitous outcomes occurred in 23.6% ( N = 74). In our study, we were able to identify structural, cognitive, and behavioral errors that contribute to GBS prophylaxis failures. In other cases, these errors may contribute to fortuitous outcomes.

Leveraging a health information exchange for analyses of COVID-19 outcomes including an example application using smoking history and mortality.

Understanding sociodemographic, behavioral, clinical, and laboratory risk factors in patients diagnosed with COVID-19 is critically important, and requires building large and diverse COVID-19 cohorts with both retrospective information and prospective follow-up. A large Health Information Exchange (HIE) in Southeast Texas, which assembles and shares electronic health information among providers to facilitate patient care, was leveraged to identify COVID-19 patients, create a cohort, and identify risk factors for both favorable and unfavorable outcomes. The initial sample consists of 8,874 COVID-19 patients ascertained from the pandemic's onset to June 12th, 2020 and was created for the analyses shown here. We gathered demographic, lifestyle, laboratory, and clinical data from patient's encounters across the healthcare system. Tobacco use history was examined as a potential risk factor for COVID-19 fatality along with age, gender, race/ethnicity, body mass index (BMI), and number of comorbidities. Of the 8,874 patients included in the cohort, 475 died from COVID-19. Of the 5,356 patients who had information on history of tobacco use, over 26% were current or former tobacco users. Multivariable logistic regression showed that the odds of COVID-19 fatality increased among those who were older (odds ratio = 1.07, 95% CI 1.06, 1.08), male (1.91, 95% CI 1.58, 2.31), and had a history of tobacco use (2.45, 95% CI 1.93, 3.11). History of tobacco use remained significantly associated (1.65, 95% CI 1.27, 2.13) with COVID-19 fatality after adjusting for age, gender, and race/ethnicity. This effort demonstrates the impact of having an HIE to rapidly identify a cohort, aggregate sociodemographic, behavioral, clinical and laboratory data across disparate healthcare providers electronic health record (HER) systems, and follow the cohort over time. These HIE capabilities enable clinical specialists and epidemiologists to conduct outcomes analyses during the current COVID-19 pandemic and beyond. Tobacco use appears to be an important risk factor for COVID-19 related death.

Development of a potential high-throughput workflow to characterize sites of bioconjugation by immuno-affinity capture coupled to MALDI-TOF mass spectrometry.

The characterization of conjugation sites in bioconjugates is critical in the early discovery phase because site-specific conjugation improves in vivo stability and drug efficacy. We previously developed an engineered monoclonal antibody (mAb) scaffold which enables site-specific conjugation toward a reactive lysine (Lys) residue on each heavy chain (HC) by using an azetidinone (AZD) linker. In order to explore conjugations in other location which avoids potential interference with target binding, other chemical linkers have been studied and the investigation of N-hydroxysuccinimade (NHS) linker is reported here. The complexity of identifying the sites lies in part to the large number of Lys residues available for conjugation on the mAb scaffold. This has posed technical challenges to standard peptide mapping approaches. Therefore, an alternative strategy intended for a rapid analysis has been investigated by coupling immuno-affinity capture to matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). In this study, we have employed a novel application of two different capture formats: Surface enhanced laser dissociation/ionization (SELDI) and mass spectrometry immunoassay (MSIA) tips to reduce the analysis time. An antibody against the pharmacophore portion was immobilized to capture the conjugated peptides, and subsequently provide characterization of the conjugation sites on the scaffold. Multiple sites for the AZD and NHS linkers have been easily identified and confirmed by MS2 sequencing. Lysine99 is the predominant site for the AZD linker, and Lysine55 is the primary site for the NHS linker with Lysine193 and Tyrosine37 being minor sites as shown in the abstract figure. We have also demonstrated the use of conjugation mapping to compare the distribution pattern between the AZD and NHS linkers as well as to study the stability of conjugation sites in a rapid way.

Effectiveness of bar coded medication alerts for elevated potassium.

Bar coded medication administration (BCMA), the automated electronic verification of medications by nurses at the patient bedside, provides an additional layer of safety to the process of medication administration in the hospital setting. We performed a retrospective, descriptive study of BCMA alerts for elevated potassium (>5.5 mg/dL) in place within a multihospital healthcare system. Overall, 642 BCMA alerts were analyzed with a 21.3% acceptance rate. In subgroup analysis, we found that the BCMA acceptance rate was 6.9% for patients aged less than one year, and 85.6% for patients aged greater than one year. The major contributing factor to the low overall acceptance rate was the high frequency of alerts in patients less than 1 year of age. Modifications to rules logic may be necessary for this specific population. While BCMA alerts can beneficial, they should be carefully implemented with periodic post-implementation analysis and refinement.

Improving erythropoietin-stimulating agent administration in a multihospital system through quality improvement initiatives: a pre-post comparison study.

INTRODUCTION: : Erythropoietin-stimulating agent (ESA) use is associated with serious adverse events in patients with hemoglobin levels of 12 g/dL or higher at the time of administration. Our aim was to determine whether inappropriate ESA use has changed over time since the implementation of new drug warning alerts and local quality improvement initiatives. MATERIALS AND METHODS: : We performed a retrospective review of ESA administration practices at Memorial Hermann Healthcare System (Houston, Tex). Our primary outcome measure was the proportion of inpatient encounters (one entire inpatient hospital stay) with 1 or more inappropriate uses of ESA (defined as ESA administration for a patient with hemoglobin ≥12 g/dL). We analyzed the potential influence of local and national interventions on ESA utilization patterns. RESULTS: : Between May 1, 2006, and May 31, 2009, 15,642 inpatients were treated with ESAs in our system. We classified inpatients as before intervention (n = 6350) and after intervention (n = 9292) based on the date of implementation of a synchronous alert in the electronic medical record. We found a significant decrease in inappropriate ESA administration before to after intervention (9.03%-6.21%; P < 0.001), which can be translated into a 31.25% (05% CI, 21.93%-40.75%) relative risk reduction. Reduced odds ratios for inappropriate ESA use changed little after controlling for relevant demographic variables and clinical characteristics. CONCLUSIONS: : Following several quality improvement interventions to improve patient safety related to ESA use, we found a significant reduction in inappropriate ESA administration to inpatients in a large health care system.

Evolution of potent and stable placental-growth-factor-1-targeting CovX-bodies from phage display peptide discovery.

Novel phage-derived peptides are the first reported molecules specifically targeting human placental growth factor 1 (PlGF-1). Phage data enabled peptide modifications that decreased IC(50) values in PlGF-1/VEGFR-1 competition ELISA from 100 to 1 µM. Peptides exhibiting enhanced potency were bioconjugated to the CovX antibody scaffold 1 (CVX-2000), generating bivalent CovX-Bodies with 2 nM K(D) against PlGF-1. In vitro and in vivo peptide cleavage mapping studies enabled the identification of proteolytic hotspots that were subsequently chemically modified. These changes decreased IC(50) to 0.4 nM and increased compound stability from 5% remaining at 6 h after injection to 35% remaining at 24 h with a ß phase half-life of 75 h in mice. In cynomolgus monkey, a 78 h ß half-life was observed for lead compound 2. The pharmacological properties of 2 are currently being explored.

Chemical generation of bispecific antibodies.

Bispecific antibodies (BsAbs) are regarded as promising therapeutic agents due to their ability to simultaneously bind two different antigens. Several bispecific modalities have been developed, but their utility is limited due to problems with stability and manufacturing complexity. Here we report a versatile technology, based on a scaffold antibody and pharmacophore peptide heterodimers, that enables rapid generation and chemical optimization of bispecific antibodies, which are termed bispecific CovX-Bodies. Two different peptides are joined together using a branched azetidinone linker and fused to the scaffold antibody under mild conditions in a site-specific manner. Whereas the pharmacophores are responsible for functional activities, the antibody scaffold imparts long half-life and Ig-like distribution. The pharmacophores can be chemically optimized or replaced with other pharmacophores to generate optimized or unique bispecific antibodies. As a prototype, we developed a bispecific antibody that binds both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) simultaneously, inhibits their function, shows efficacy in tumor xenograft studies, and greatly augments the antitumor effects of standard chemotherapy. This unique antiangiogenic bispecific antibody is in phase-1 clinical trials.

Combined use of immunoassay and two-dimensional liquid chromatography mass spectrometry for the detection and identification of metabolites from biotherapeutic pharmacokinetic samples.

Peptides and monoclonal antibodies have both emerged as important therapeutic modalities, but each has challenges which limit their use. Non-recombinant chemical conjugation of peptides onto antibodies has the potential to minimize or eliminate altogether many of these limitations. Once such approach, pioneered by CovX has created the possibility for rapid stoichiometric fusion of pharmacophores to a single antibody platform. These molecules, called CovX-Bodies, maintain both the pharmacologic properties of a given peptide and the pharmacokinetic properties of a monoclonal antibody. The result is a new class of molecules wherein each component contributes desirable traits. In this paper, we demonstrate the use of immunoassay and two-dimensional liquid chromatography mass spectrometry (2DLC/MS) in combination to investigate the antibody conjugates of Glucagon-like peptide-1 (GLP-1) and analogs for intact protein metabolite identification directly from mouse serum. The information gained from combining these approaches has helped guide and expedite the optimization of our drug product development efforts.

Straight talk--new approaches in healthcare. The road to a digital healthcare community. Panel discussion.

Healthcare organizations are often criticized for skeptically deferring the purchase of information technologies that can improve the safety, quality and efficiency of patient care. But some forward-thinking healthcare organizations have broken out of the pack, leveraging leading-edge technologies to gain a competitive advantage. They integrate information technologies across the enterprise, allowing them to compress processes, adapt to market forces and generate the kind of quality data that payers, physicians and patients expect. In this installment of Straight Talk, we discuss the strategies that three organizations have deployed successfully to move themselves along the digital continuum. Modern Healthcare and PricewaterhouseCoopers present Straight Talk. The session on digital healthcare was held on May 3, 2005 at Modern Healthcare's Chicago headquarters. Fawn Lopez, publisher of Modern Healthcare, was the moderator.