Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

Comparability of Elezanumab Safety, Tolerability, and Pharmacokinetics in Healthy Japanese, Chinese, and White Participants.

Elezanumab is a fully human monoclonal antibody, which is directed against repulsive guidance molecule A. The safety, tolerability, pharmacokinetics (PK), and immunogenicity of elezanumab were assessed in 2 Phase 1 clinical studies. The objective of this study was to assess the PK, safety, tolerability, and immunogenicity following intravenous infusion of elezanumab in healthy adult Japanese, Han Chinese, and Caucasian participants as well as Western participants from the single-ascending-dose study. Elezanumab exposures were approximately 20% higher in Japanese and Han Chinese participants compared to White participants without controlling for body weight. After statistically controlling for body weight by including it as a covariate, the PK of elezanumab in White participants were comparable to those in Japanese and Han Chinese participants. The clinical implications of these exposure differences are yet to be determined. All adverse events were assessed by the investigator as having no reasonable possibility of being related to the study drugs and were mild in severity. No positive immunogenicity effect was observed that impacted elezanumab exposure or safety.

Feasibility of and Experience with Free State Funded Telehealth Based Patient Self-referral for COVID-19 Monoclonal Antibody Therapy.

BACKGROUND: Monoclonal antibody (mAb) treatment for COVID-19 has been underutilized due to logistical challenges, lack of access and variable treatment awareness among patients and healthcare professionals. The use of telehealth during the pandemic provides an opportunity to increase access to COVID-19 care. METHODS: This is a single-center descriptive study of telehealth-based patient self-referral for mAb therapy between March 1, 2021, to October 31, 2021 at Baltimore Convention Center Field Hospital (BCCFH). RESULTS: Among the 1001 self-referral patients, the mean age was 47, and most were female (57%) white (66%), and had a primary care provider (62%). During the study period, self-referrals increased from 14 per month in March to 427 in October resulting in a 30-fold increase. About 57% of self-referred patients received a telehealth visit, and of those 82% of patients received mAb infusion therapy. The median time from self-referral to onsite infusion was 2 days (1-3 IQR). DISCUSSION: Our study shows the integration of telehealth with a self-referral process improved access to mAb infusion. A high proportion of self-referrals were appropriate and led to timely treatment. This approach helped those without traditional avenues for care and avoided potential delay for patients seeking referral from their PCPs.

Accuracy of Expired BinaxNOW Rapid Antigen Tests.

The widespread existence of expired antigen testing kits in households and potential coronavirus outbreaks necessitates evaluating the reliability of these expired kits. Our study examined BinaxNOW COVID-19 rapid antigen tests 27 months postmanufacture and 5 months past their FDA extended expiration dates, using SARS-CoV-2 variant XBB.1.5 viral stock. We conducted testing at two concentrations, the limit of detection (LOD) and 10 times the LOD. One hundred expired and unexpired kits were tested at each concentration for a total of 400 antigen tests. At the LOD (2.32 × 102 50% tissue culture infective dose/mL [TCID50/mL]), both expired and unexpired tests displayed 100% sensitivity (95% confidence interval [CI], 96.38% to 100%), with no statistical difference (95% CI, -3.92% to 3.92%). Similarly, at 10 times the LOD, unexpired tests retained 100% sensitivity (95% CI, 96.38% to 100%), while expired tests exhibited 99% sensitivity (95% CI, 94.61% to 99.99%), demonstrating a statistically insignificant 1% difference (95% CI, -2.49% to 4.49%; P = 0.56). Expired rapid antigen tests had fainter lines than the unexpired tests at each viral concentration. The expired rapid antigen tests at the LOD were only just visible. These findings carry significant implications for waste management, cost efficiency, and supply chain resilience in pandemic readiness efforts. They also provide critical insights for formulating clinical guidelines for interpreting results from expired kits. In light of expert warnings of a potential outbreak of a severity rivaling the Omicron variant, our study underscores the importance of maximizing the utility of expired antigen testing kits in managing future health emergencies. IMPORTANCE The study examining the reliability of expired antigen testing kits in the context of COVID-19 has significant real-world implications. By demonstrating that these expired kits retain their sensitivity in detecting the virus, this work provides evidence that expired kits can still be utilized, reducing waste and optimizing resources in health care systems. These findings are especially crucial in light of potential future coronavirus outbreaks and the need to be prepared. The study's outcomes have the potential to contribute to waste management efforts, cost efficiency, and supply chain resilience, ensuring that diagnostic tests remain readily available for effective public health interventions. Furthermore, it provides critical insights for formulating clinical guidelines on interpreting results from expired kits, enhancing the accuracy of testing outcomes, and supporting informed decision-making. Ultimately, this work holds great importance in maximizing the utility of expired antigen testing kits, safeguarding public health, and enhancing pandemic readiness on a global scale.

High Sensitivity and NPV for BinaxNOW Rapid Antigen Test in Children at a Mass Testing Site during Prevalent Delta Variant Period.

SARS-CoV-2 continues to develop new, increasingly infectious variants including delta and omicron. We evaluated the efficacy of the Abbott BinaxNOW Rapid Antigen Test against Reverse Transcription PCR (RT-PCR) in 1,054 pediatric participants presenting to a high-volume Coronavirus Disease 2019 (COVID-19) testing site while the delta variant was predominant. Both tests utilized anterior nares swabs. Participants were grouped by COVID-19 exposure and symptom status. 5.2% of samples tested positive by RT-PCR for SARS-CoV-2. For all participants, sensitivity of the BinaxNOW was 92.7% (95% CI 82.4%-98.0%), and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, positive predictive value (PPV) was 72.7% (95% CI 54.5%-86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2%-100%). Among asymptomatic participants, PPV was 71.4% (95% CI 53.7%-85.4%) and NPV was 99.7% (95% CI 99.0%-100%). Our reported sensitivity and NPV are higher than other pediatric studies, potentially because of higher viral load from the delta variant, but specificity and PPV are lower. IMPORTANCE The BinaxNOW rapid antigen COVID-19 test had a sensitivity of nearly 92% in both symptomatic and asymptomatic children when performed at a high-throughput setting during the more transmissible delta variant dominant period. The test may play an invaluable role in asymptomatic screening and keeping children safe in school.

Potential Financial Effects on Hospitals of the Removal of Common Orthopaedic and Spinal Procedures From Medicare's "Inpatient-Only" List: A Comparison of the Medicare Fee-for-service Payment Model Versus Maryland's Global Budget Revenue Model.

BACKGROUND: When treating Medicare beneficiaries, orthopaedic surgeons must follow Centers for Medicare & Medicaid Services (CMS) policies regarding whether to perform surgical treatments under inpatient or outpatient status. Recently, most orthopaedic and spinal procedures were removed from the CMS's "inpatient-only" list (IPOL). We investigated differences in hospital payments under the Diagnosis Related Group (DRG)/Ambulatory Payment Classification (APC) system when common orthopaedic/spinal procedures are done under outpatient rather than inpatient status. We compared these differences under the DRG/APC model with differences in payments to Maryland hospitals, which are paid under the alternative Global Budget Revenue model. METHODS: We used the CMS Inpatient Pricer and CMS Addendum B to retrieve the mean duration-of-stay data, estimated DRG (inpatient) payment, and APC (outpatient) payment for eight common orthopaedic/spinal procedures for four non-Maryland hospitals (2 urban academic hospitals and 2 neighboring community hospitals). We retrieved Maryland's Health Services Cost Review Commission hospital rates for the same eight procedures done under inpatient or outpatient status to estimate hospital charges for a Maryland urban academic hospital and a neighboring community hospital. RESULTS: Among the four non-Maryland hospitals, estimated differences in payment for hospitalizations under inpatient versus outpatient status for common orthopaedic/spinal procedures with a mean duration of stay of <2 days, whose status would be most subject to change from inpatient to outpatient by its removal from the IPOL, ranged from $19 to $13,042. For the two Maryland hospitals, differences in outpatient versus inpatient payment for these same procedures ranged from $182 to $1,273. DISCUSSION: Non-Maryland hospitals receive widely different CMS payments for common orthopaedic/spinal procedures based on a change in hospitalization status (inpatient to outpatient) prompted by the procedure being removed from the IPOL. The Maryland global budget revenue mitigates most of the effect of hospitalization status on hospital payment and may serve as a guide toward DRG/APC payment reassessment. LEVEL OF EVIDENCE: N/A.

The increasing impact of length of stay "outliers" on length of stay at an urban academic hospital.

BACKGROUND: As healthcare systems strive for efficiency, hospital "length of stay outliers" have the potential to significantly impact a hospital's overall utilization. There is a tendency to exclude such "outlier" stays in local quality improvement and data reporting due to their assumed rare occurrence and disproportionate ability to skew mean and other summary data. This study sought to assess the influence of length of stay (LOS) outliers on inpatient length of stay and hospital capacity over a 5-year period at a large urban academic medical center. METHODS: From January 2014 through December 2019, 169,645 consecutive inpatient cases were analyzed and assigned an expected LOS based on national academic center benchmarks. Cases in the top 1% of national sample LOS by diagnosis were flagged as length of stay outliers. RESULTS: From 2014 to 2019, mean outlier LOS increased (40.98 to 45.11 days), as did inpatient LOS with outliers excluded (5.63 to 6.19 days). Outlier cases increased both in number (from 297 to 412) and as a percent of total discharges (0.98 to 1.56%), and outlier patient days increased from 6.7 to 9.8% of total inpatient plus observation days over the study period. CONCLUSIONS: Outlier cases utilize a disproportionate and increasing share of hospital resources and available beds. The current tendency to exclude such outlier stays in data reporting due to assumed rare occurrence may need to be revisited. Outlier stays require distinct and targeted interventions to appropriately reduce length of stay to both improve patient care and maintain hospital capacity.

Elezanumab, a human anti-RGMa monoclonal antibody, promotes neuroprotection, neuroplasticity, and neurorecovery following a thoracic hemicompression spinal cord injury in non-human primates.

Spinal cord injury (SCI) is a devastating condition characterized by loss of function, secondary to damaged spinal neurons, disrupted axonal connections, and myelin loss. Spontaneous recovery is limited, and there are no approved pharmaceutical treatments to reduce ongoing damage or promote repair. Repulsive guidance molecule A (RGMa) is upregulated following injury to the central nervous system (CNS), where it is believed to induce neuronal apoptosis and inhibit axonal growth and remyelination. We evaluated elezanumab, a human anti-RGMa monoclonal antibody, in a novel, newly characterized non-human primate (NHP) hemicompression model of thoracic SCI. Systemic intravenous (IV) administration of elezanumab over 6 months was well tolerated and associated with significant improvements in locomotor function. Treatment of animals for 16 weeks with a continuous intrathecal infusion of elezanumab below the lesion was not efficacious. IV elezanumab improved microstructural integrity of extralesional tissue as reflected by higher fractional anisotropy and magnetization transfer ratios in treated vs. untreated animals. IV elezanumab also reduced SCI-induced increases in soluble RGMa in cerebrospinal fluid, and membrane bound RGMa rostral and caudal to the lesion. Anterograde tracing of the corticospinal tract (CST) from the contralesional motor cortex following 20 weeks of IV elezanumab revealed a significant increase in the density of CST fibers emerging from the ipsilesional CST into the medial/ventral gray matter. There was a significant sprouting of serotonergic (5-HT) fibers rostral to the injury and in the ventral horn of lower thoracic regions. These data demonstrate that 6 months of intermittent IV administration of elezanumab, beginning within 24 h after a thoracic SCI, promotes neuroprotection and neuroplasticity of key descending pathways involved in locomotion. These findings emphasize the mechanisms leading to improved recovery of neuromotor functions with elezanumab in acute SCI in NHPs.

Improving Healthcare Value: COVID-19 Emergency Regulatory Relief and Implications for Post-Acute Skilled Nursing Facility Care.

Rarely, if ever, does a national healthcare system experience such rapid and marked change as that seen with the COVID-19 pandemic. In March 2020, the president of the United States declared a national health emergency, enabling the Department of Health & Human Services authority to grant temporary regulatory waivers to facilitate efficient care delivery in a variety of healthcare settings. The statutory requirement that Medicare beneficiaries stay three consecutive inpatient midnights to qualify for post-acute skilled nursing facility coverage is one such waiver. This so-called Three Midnight Rule, dating back to the 1960s as part of the Social Security Act, is being scrutinized more than half a century later given the rise in observation hospital stays. Despite the tragic emergency circumstances prompting waivers, the Centers for Medicare & Medicaid Services and Congress now have a unique opportunity to evaluate potential improvements revealed by COVID-19 regulatory relief and should consider permanent reform of the Three Midnight Rule.

Learning From Lawsuits: Using Malpractice Claims Data to Develop Care Transitions Planning Tools.

OBJECTIVES: Our understanding of care transitions from hospital to home is incomplete. Malpractice claims are an important and underused data source to understand such transitions. We used malpractice claims data to (1) evaluate safety risks during care transitions and (2) help develop care transitions planning tools and pilot test their ability to evaluate care transitions from the hospital to home. METHODS: Closed malpractice claims were analyzed for 230 adult patients discharged from 4 hospital sites. Stakeholders participated in 2 structured focus groups to review concerns. This led to the development of 2 care transitions planning tools-one for patients/caregivers and one for frontline care providers. Both were tested for feasibility on 53 patient discharges. RESULTS: Qualitative analysis yielded 33 risk factors corresponding to hospital work system elements, care transitions processes, and care outcomes. Providers reported that the tool was easy to use and did not adversely affect workflow. Patients reported that the tool was acceptable in terms of length and response burden. Patients were often still waiting for information at the time they applied the tool. CONCLUSIONS: Malpractice claims provided insights that enriched our understanding of suboptimal care transitions and guided the development of care transitions planning tools. Pilot testing suggested that the tools would be feasible for use with minor adjustment. The malpractice data can complement other approaches to characterize systems failures threatening patient safety.

Levodopa-carbidopa intestinal gel high concentration formulation is clinically bioequivalent to commercial formulation.

A new levodopa-carbidopa intestinal gel (LCIG) system featuring a higher levodopa/carbidopa (LD/CD) concentration and viscosity, LCIG-HV, is being developed to reduce the intrajejunal volume of LD/CD that is administered as compared to the current commercial formulation, LCIG-LV. This study characterizes the LCIG-HV formulation and compares it to the LCIG-LV formulation via dissolution testing and a clinical pharmacokinetic bioequivalence study. In vitro release profiles of LD/CD were determined using a USP Dissolution Apparatus 2 with 500 mL of phosphate buffer (pH 4.5) operating at 25 RPM. A single dose, open-label study was conducted according to a two-period, randomized, crossover design in 28 healthy subjects. The point estimate (PE) of the levodopa Cmax geometric mean for the LCIG-HV formulation was 4% higher than that of the LCIG-LV formulation. PEs of levodopa AUCt and AUCinf geometric means were comparable for both formulations. PEs of carbidopa Cmax , AUCt and AUCinf geometric means for the LCIG-HV formulation were 3%-5% higher than those of the LCIG-LV formulation. For both formulations, the median Tmax for levodopa was 1.0 and 3.0 hours for carbidopa. The levodopa half-life harmonic mean was 1.6 hour for both formulations. The carbidopa half-life harmonic mean was 1.9 and 2.0 hour, respectively, for the LCIG-HV and LCIG-LV formulations. Cmax , AUCt and AUCinf of LD/CD carbidopa were comparable for both formulations. The current study demonstrates that the LCIG-LV and LCIG-HV formulations are clinically bioequivalent for LD/CD according to FDA guidance. However, the dissolution method was over discriminatory of formulation differences.

Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of Alicapistat, a Selective Inhibitor of Human Calpains 1 and 2 for the Treatment of Alzheimer Disease: An Overview of Phase 1 Studies.

Alicapistat is an orally active selective inhibitor of calpain 1 and 2 whose overactivation has been linked to Alzheimer disease (AD). Three studies were conducted in healthy subjects (18-55 years), 1 in healthy elderly subjects (≥65 years), and 1 in patients with mild to moderate AD. Four studies assessed pharmacokinetics, 1 study in healthy subjects assessed pharmacodynamics (sleep parameters, particularly rapid eye movement [REM], as a measure of central nervous system [CNS] penetration and activity), and all studies assessed safety. Participants received single doses or multiple twice-daily doses of alicapistat for up to 14 days. Maximum alicapistat plasma concentrations were reached in 2 to 5 hours; half-life was 7 to 12 hours postdose. Alicapistat exposure was dose proportional in the alicapistat 50- to 1000-mg dose range. Exposure of the alicapistat R,S diastereomer was approximately 2-fold greater than exposure of the R,R diastereomer in healthy young and elderly subjects and patients with AD. Alicapistat at 400- or 800-mg twice-daily doses had no effect on REM sleep parameters, whereas the active control, donepezil at 10 mg twice daily, affected sleep parameters. Across all trials, the incidence of treatment-emergent adverse events was similar in the placebo and alicapistat groups. There were no clinically significant changes in vital signs and laboratory measurements. The lack of an effect of alicapistat on sleep suggests that concentrations in the CNS were inadequate or that preclinical studies do not predict alicapistat effects in humans.

Methotrexate Dose in Patients With Early Rheumatoid Arthritis Impacts Methotrexate Polyglutamate Pharmacokinetics, Adalimumab Pharmacokinetics, and Efficacy: Pharmacokinetic and Exposure-response Analysis of the CONCERTO Trial.

PURPOSE: Methotrexate (MTX) and adalimumab are well-recognized treatments of rheumatoid arthritis (RA), the efficacy of which may be driven by intracellular polyglutamates (PGs). The aim of this analysis was to characterize MTX PG concentrations and adalimumab pharmacokinetics in the CONCERTO trial. In addition, the relationships between MTX dose/pharmacokinetics, adalimumab pharmacokinetics, and efficacy were evaluated. METHODS: CONCERTO was a double-blind, parallel-arm study in patients with early RA randomized to adalimumab 40 mg SC every other week plus blinded MTX 2.5, 5, 10, or 20 mg PO once weekly, for 26 weeks. Blood samples were obtained through week 26 for the determination of concentrations of MTX PG, adalimumab, and anti-adalimumab antibody (AAA). Clinical outcomes were also assessed. FINDINGS: A total of 395 patients were included in the analysis (MTX, 329; adalimumab, 395). The mean time to steady-state MTX PG concentration was increased with MTX dose, from 8 to >26 weeks, depending on PG chain length. Dose proportionality changed with PG chain length. As MTX dose was increased, the percentage of short-chain PGs increased less than dose proportionally, while the percentage of long-chain PGs increased more than dose proportionally. For very-long-chain PGs, dose proportionality could not be assessed due to the nonmeasurable concentrations in the 2.5- and 5-mg MTX dose groups. As MTX dose increased, mean adalimumab concentrations also increased (P < 0.001). The percentage of patients with AAA decreased with increasing MTX dose, and at week 26, AAA+ status was significantly correlated with MTX dose level (P = 0.005). In general, rates of response, defined using the 28-joint count disease activity score based on C-reactive protein (DAS28[CRP]; response, <3.2), were greater in the subgroup without AAA. The likelihood of a patient achieving a DAS28(CRP) response was related to the baseline measurement (P < 0.001) and to the concentration of adalimumab (P = 0.001), but not to the MTX regimen (P = 0.689). IMPLICATIONS: The dose-response characteristics of MTX PG pharmacokinetics and the resultant effects of MTX on adalimumab exposures should be considered when determining the benefit-risk profile of MTX and adalimumab combination therapy in patients with early RA. ClinicalTrials.gov identifier: NCT01185301.

Hospitalizations With Observation Services and the Medicare Part A Complex Appeals Process at Three Academic Medical Centers.

Hospitalists and other providers must classify hospitalized patients as inpatient or outpatient, the latter of which includes all observation stays. These orders direct hospital billing and payment, as well as patient out-of-pocket expenses. The Centers for Medicare & Medicaid Services (CMS) audits hospital billing for Medicare beneficiaries, historically through the Recovery Audit program. A recent U.S. Government Accountability Office (GAO) report identified problems in the hospital appeals process of Recovery Audit program audits to which CMS proposed reforms. In the context of the GAO report and CMS's proposed improvements, we conducted a study to describe the time course and process of complex Medicare Part A audits and appeals reaching Level 3 of the 5-level appeals process as of May 1, 2016 at 3 academic medical centers. Of 219 appeals reaching Level 3, 135 had a decision--96 (71.1%) successful for the hospitals. Mean total time since date of service was 1663.3 days, which includes mean days between date of service and audit (560.4) and total days in appeals (891.3). Government contractors were responsible for 70.7% of total appeals time. Overall, government contractors and judges met legislative timeliness deadlines less than half the time (47.7%), with declining compliance at successive levels (discussion, 92.5%; Level 1, 85.4%; Level 2, 38.8%; Level 3, 0%). Most Level 1 and Level 2 decision letters (95.2%) cited time-based (24-hour) criteria for determining inpatient status, despite 70.3% of denied appeals meeting the 24-hour benchmark. These findings suggest that the Medicare appeals system merits process improvement beyond current proposed reforms. Journal of Hospital Medicine 2017;12:251-255.