Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 and Variants Using Digital Droplet Polymerase Chain Reaction at a Large University and Healthcare System in California.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with different infectivity, transmission potential, and morbidity change the characteristics of local epidemics and affect vaccine effectiveness. As part of the University of Southern California COVID-19 Pandemic Research Center's efforts to understand, control, and inform local community on coronavirus disease 2019 (COVID-19), we implemented a SARS-CoV-2 surveillance program among students, employees, and USC Keck Medical Center patients. We present the epidemiology and distribution of SARS-CoV-2 and its variants among the population. Methods: We used digital droplet reverse-transcriptase polymerase chain reaction (PCR) to analyze in real-time remnant SARS-CoV-2 PCR-positive saliva specimens stored at the USC Keck Medicine laboratory between September 2020 and April 2022. Samples were tested for the original strain (A20) and 9 SARS-CoV-2 variants: α(B.1.1.7, Q.1-Q.8), ß(B.1.351, B.1.351.2, B.1.351.3), γ(P.1, P.1.1, P.1.2), δ(B.1.617.2), δ+(or δ417N), ε(B.1.427 and B.1.429), η(B.1.525), λ(C.37) and ο(B.1.1.529, ΒΑ.1, BA.2). We reviewed deidentified health information from positive cases including demographics, history of COVID-19 (eg, symptoms, hospitalizations, and repeat infections), and COVID-19 vaccination status. Results: We reviewed 1169 cases and determined the variant type of 482 specimens: 77 specimens were original strain, 119 "Delta", 165 "Omicron". The original strain was detected during the third and fourth quarters of 2020. The Delta variant appeared during the second quarter of 2021, whereas Omicron appeared in the fourth quarter of 2021. Conclusions: Prospectively tracking SARS-CoV-2 variants in a university population and a hospital system, utilizing a low-cost, high-throughput PCR assay, was feasible. Local variant monitoring remains important to inform prevention and control efforts among university and clinical settings.

Medical and nursing home costs: From cognitively unimpaired through dementia.

INTRODUCTION: Efforts to model the cost-effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing-home (NH) costs. METHODS: A stratified-random sample of Olmsted County, MN, residents ages 70-89 years (N = 3545), well-characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider-linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH-use intensity (NH days/follow-up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between-category mean-annual cost differences were adjusted for patient characteristics and follow-up days. RESULTS: Costs/follow-up day distributions differed significantly across cognitive categories. Mean costs/follow-up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted-between-category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired. DISCUSSION: Cost-effectiveness for managing/modifying both MCI and dementia should consider end-of-life costs and NH-use intensity. Results can help inform cost-effectiveness models, predict future-care needs, and aid decision-making by individuals/providers/payers/policymakers.

Electromagnetic acoustic imaging methods: resolution, signal-to-noise, and image contrast in phantoms.

Purpose: Electromagnetic acoustic imaging (EMAI) is a hybrid imaging technique using radio-frequency irradiation to induce ultrasound (US), providing an US image in which spatial conductivity differences provide image contrast. The method is potentially clinically important in that the added diagnostic parameter has been shown to be useful in cancer detection and vascular space delineation. Approach: We report the development of coil configurations and imaging processing techniques designed to address the low signal-to-noise of EMAI and demonstrate achievable resolution and contrast in phantoms along with EMAI signals in excised animal tissue. Experiment results are compared with theoretical calculations. Results: EMAI signal intensities depend on the square of the ampere-turns in the coil radio frequency coil as predicted theoretically. Resolution is shown to be comparable to conventional US imaging with contrast and signal intensity depending on source conductivity. Optimizing signal-to-noise depends on coil design, orientation of the electromagnetic fields, and coherent processing. Conclusions: Two-dimensional EMAI images are shown to have the expected resolution of conventional US with image contrast dependent on conductivity. Achievable signal-to-noise is sufficient to form potentially clinically useful images.

High-precision and cost-efficient sequencing for real-time COVID-19 surveillance.

COVID-19 global cases have climbed to more than 33 million, with over a million total deaths, as of September, 2020. Real-time massive SARS-CoV-2 whole genome sequencing is key to tracking chains of transmission and estimating the origin of disease outbreaks. Yet no methods have simultaneously achieved high precision, simple workflow, and low cost. We developed a high-precision, cost-efficient SARS-CoV-2 whole genome sequencing platform for COVID-19 genomic surveillance, CorvGenSurv (Coronavirus Genomic Surveillance). CorvGenSurv directly amplified viral RNA from COVID-19 patients' Nasopharyngeal/Oropharyngeal (NP/OP) swab specimens and sequenced the SARS-CoV-2 whole genome in three segments by long-read, high-throughput sequencing. Sequencing of the whole genome in three segments significantly reduced sequencing data waste, thereby preventing dropouts in genome coverage. We validated the precision of our pipeline by both control genomic RNA sequencing and Sanger sequencing. We produced near full-length whole genome sequences from individuals who were COVID-19 test positive during April to June 2020 in Los Angeles County, California, USA. These sequences were highly diverse in the G clade with nine novel amino acid mutations including NSP12-M755I and ORF8-V117F. With its readily adaptable design, CorvGenSurv grants wide access to genomic surveillance, permitting immediate public health response to sudden threats.

Accuracy and Precision of the SynchroMed II Pump.

OBJECTIVE: The objective of this study was to evaluate the accuracy and precision of SynchroMed II programmable infusion pumps for delivery of intrathecal baclofen to treat severe spasticity. DESIGN: Retrospective chart review study. SETTING: Urban academic rehabilitation clinic. PATIENTS (OR PARTICIPANTS): Patients with spasticity treated with intrathecal baclofen. METHODS OR INTERVENTIONS (OR ASSESSMENT OF RISK FACTORS): A retrospective chart review of 149 patients inclusive of 755 individual patient encounters more than a 2.5-year span for baclofen pump refills was performed. MAIN OUTCOME MEASUREMENTS: Charts were reviewed to obtain data on the concentration and dose of intrathecal baclofen, aspirated and residual volumes, age of the pump, and reservoir volume of the pump. Flow rate (mL/day) was calculated for each chronological visit. Flow rates from clinical data were used to calculate the accuracy and precision based on the manufacturer's specifications for both the 20 mL and 40 mL pumps. RESULTS: The infused volume accuracy and precision of both the 20 mL pumps and 40 mL pumps remained within manufacturer's specifications while delivering drug at a rate slightly lower than predicted. There were no cases of pump over-infusion. There is a statistically significant decrease in flow rate accuracy over the lifespan of the pump. CONCLUSIONS: SynchroMed II pumps infuse at slightly less than their predicted rate while remaining within the manufacturer's specifications. No pump over-infusions were noted. Pump flow rate declines over time. Further study is warranted to assess the impact of this flow rate decrease on patient treatment and safety.

Atlantoaxial Instability Resulting in Intractable Nausea in a Person with C5 Complete Spinal Cord Injury: A Case Report.

Individuals with spinal cord injury (SCI) have altered neurophysiology and present with symptoms that must be interpreted in the context of their specific neurologic injury. This is a case of a 16-year-old female adolescent with C5 American Spinal Injury Association Impairment Scale A SCI who presented with intractable nausea. Multiple etiologies for her nausea, including medication effect, metabolic and gastrointestinal disorders, autonomic dysreflexia, and mood disorder, were systematically ruled out. Due to the persistence of the patient's symptoms and suboptimal progression in her rehabilitation, a central nervous system etiology was investigated. Ultimately, atlantoaxial instability with odontoid compression on the medulla was identified and her refractory nausea resolved following an occiput to C2 fusion. To our knowledge, this is the first reported case of atlantoaxial instability causing intractable nausea due to brain stem compression in a patient with SCI. Level of Evidence: V.

Venous Thromboembolism (VTE) Incidence and VTE-Associated Survival among Olmsted County Residents of Local Nursing Homes.

Nursing home (NH) residency is an independent risk factor for venous thromboembolism (VTE), but the VTE burden within the NH population is uncertain. This study estimates VTE incidence and VTE-associated mortality among NH residents. We identified all NH residents in any NH in Olmsted County, Minnesota, United States, 1 October 1998 to 31 December 2005 and all first lifetime VTE among county residents to estimate VTE incidence while resident of local NHs (NHVTE), using Centers for Medicare and Medicaid Services Minimum Data Set and Rochester Epidemiology Project resources. We tested associations between NHVTE and age, sex and time since each NH admission using Poisson modelling. Additionally, we tested incident NHVTE as a potential predictor of survival using Cox proportional hazards, adjusting for age, sex and NH residency. Between 1 October 1998 and 31 December 2005, 3,465 Olmsted County residents with ≥1 admission to a local NH, contributed 4,762 NH stays. Of the 3,465 NH residents, 111 experienced incident NHVTE (2.3% of all eligible stays), for an overall rate of 3,653/100,000 NH person-years (NH-PY). VTE incidence was inversely associated with time since each NH admission, and was highest in the first 7 days after each NH admission (18,764/100,000 NH-PY). The adjusted hazard of death for incident NHVTE was 1.90 (95% confidence interval [CI]: 1.38-2.62). In conclusion, VTE incidence among NH residents was nearly 30-fold higher than published incidence rates for the general Olmsted County population. VTE incidence was highest within 7 days after NH admission, and NHVTE was associated with significantly reduced survival. These data can inform future research and construction of clinical trials regarding short-term prophylaxis.

Sterilizing photocurable materials by irradiation: preserving UV-curing properties of photopolymers following E-beam, gamma, or X-ray exposure.

We have developed novel photopolymer gels to function as separators in blood collection tubes. By incorporating antioxidants such as α-tocopherol and nitroxides (TEMPO and TEMPOL), the new formulation can be sterilized with electron beam or gamma rays at a dose level of 17 kGy, without inducing premature curing of the photopolymers. For the blood separator gels that contain α-tocopherol, our results show that α-tocopherol plays a decisive role in impeding C-centered free radical propagation reactions through an H-transfer mechanism. This mechanism involves the transfer of an H-atom from the hydroxyl group (OH) of α-tocopherol to the propagating C-centered radical leading to the termination of the polymerization. The sterilization radiation-induced premature curing of the photopolymer was also prevented in the blood separator gel containing nitroxides. For the gels containing TEMPO or TEMPOL, inhibition of the premature curing was achieved through an addition reaction or an H-transfer reaction, respectively. Our results also show that while α-tocopherol is not a contributing factor in the subsequent (time-of-use) UV curing of the gels, nitroxides enhance the UV curing process through nitroxide-mediated living free radical polymerization reactions leading to a decrease in UV curing time. The photopolymer separator gels are shown to function advantageously in clinical laboratory testing, especially for cell-free DNA measurements in blood.

Nursing Home Use Across The Spectrum of Cognitive Decline: Merging Mayo Clinic Study of Aging With CMS MDS Assessments.

BACKGROUND/OBJECTIVES: Objective, complete estimates of nursing home (NH) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs. DESIGN: Retrospective longitudinal study. SETTING: Olmsted County, MN. PARTICIPANTS: Mayo Clinic Study of Aging participants assessed as cognitively normal (CN), mild cognitive impairment (MCI), previously unrecognized dementia, or prevalent dementia (age = 70-89 years; N = 3,545). MEASUREMENTS: Participants were followed in Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS) NH records and in Rochester Epidemiology Project provider-linked medical records for 1-year after assessment of cognition for days of observation, NH use (yes/no), NH days, NH days/days of observation, and mortality. RESULTS: In the year after cognition was assessed, for persons categorized as CN, MCI, previously unrecognized dementia, and prevalent dementia respectively, the percentages who died were 1.0%, 2.6%, 4.2%, 21%; the percentages with any NH use were 3.8%, 8.7%, 19%, 40%; for persons with any NH use, median NH days were 27, 38, 120, 305, and median percentages of NH days/days of observation were 7.8%, 12%, 33%, 100%. The year after assessment, among persons with prevalent dementia and any NH use, >50% were a NH resident all days of observation. Pairwise comparisons revealed that each increase in cognitive impairment category exhibited significantly higher proportions with any NH use. One-year mortality was especially high for persons with prevalent dementia and any NH use (30% vs 13% for those with no NH use); 58% of all deaths among persons with prevalent dementia occurred while a NH resident. CONCLUSIONS: Findings suggest reductions in NH use could result from quality alternatives to NH admission, both among persons with MCI and persons with dementia, together with suitable options for end-of-life care among persons with prevalent dementia.

Growth characteristics in cerebral palsy subtypes: a comparative assessment.

AIM: Children with quadriplegic cerebral palsy (CP) have been found to have growth rates that differ from those of children with typical development. Little research has been performed to distinguish whether growth patterns in hemiplegic, diplegic, and quadriplegic CP differ from one another. The purpose of this study was to compare growth of children with quadriplegic, hemiplegic, and diplegic CP. METHOD: Retrospective data were collected from the electronic medical record of patients with CP at an outpatient center. Linear mixed models were used to examine growth by diagnosis, using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes 343.0 (diplegia), 343.1 (hemiplegia), and 343.2 (quadriplegia). RESULTS: Heights and weights of children with quadriplegic CP were consistently lower than those with hemiplegic or diplegic CP. Children with hemiplegic CP had greater heights and weights than other CP subtypes. There were statistically significant differences in weight gain curves among the three diagnoses for males (p<0.05). INTERPRETATION: Our study reveals differences in growth rates between hemiplegic, diplegic, and quadriplegic CP subtypes.

Contributions of increasing obesity and diabetes to slowing decline in subclinical coronary artery disease.

BACKGROUND: Our previous study of nonelderly adult decedents with nonnatural (accident, suicide, or homicide) cause of death (96% autopsy rate) between 1981 and 2004 revealed that the decline in subclinical coronary artery disease (CAD) ended in the mid-1990s. The present study investigated the contributions of trends in obesity and diabetes mellitus to patterns of subclinical CAD and explored whether the end of the decline in CAD persisted. METHODS AND RESULTS: We reviewed provider-linked medical records for all residents of Olmsted County, Minnesota, who died from nonnatural causes within the age range of 16 to 64 years between 1981 and 2009 and who had CAD graded at autopsy. We estimated trends in CAD risk factors including age, sex, systolic blood pressure, diabetes (qualifying fasting glucose or medication), body mass index, smoking, and diagnosed hyperlipidemia. Using multiple regression, we tested for significant associations between trends in CAD risk factors and CAD grade and assessed the contribution of trends in diabetes and obesity to CAD trends. The 545 autopsied decedents with recorded CAD grade exhibited significant declines between 1981 and 2009 in systolic blood pressure and smoking and significant increases in blood pressure medication, diabetes, and body mass index ≥30 kg/m(2). An overall decline in CAD grade between 1981 and 2009 was nonlinear and ended in 1994. Trends in obesity and diabetes contributed to the end of CAD decline. CONCLUSIONS: Despite continued reductions in smoking and blood pressure values, the previously observed end to the decline in subclinical CAD among nonelderly adult decedents was apparent through 2009, corresponding with increasing obesity and diabetes in that population.

Direct medical costs and source of cost differences across the spectrum of cognitive decline: a population-based study.

BACKGROUND: Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild cognitive impairment (MCI), newly discovered dementia, and prevalent dementia. METHODS: Subjects were a subset of the Mayo Clinic Study of Aging stratified-random sampling of Olmsted County, MN, residents aged 70 to 89 years. A neurologist reviewed provider-linked medical records to identify prevalent dementia (review date = index). Remaining subjects were invited to participate in prospective clinical/neuropsychological assessments; participants were categorized as CN, MCI, or newly discovered dementia (assessment date = index). Costs for medical services/procedures 1-year pre-index (excluding indirect and long-term care costs) were estimated using line-item provider-linked administrative data. We estimated contributions of care-delivery site and comorbid conditions (including and excluding neuropsychiatric diagnoses) to between-category cost differences. RESULTS: Annual mean medical costs for CN, MCI, newly discovered dementia, and prevalent dementia were $6042, $6784, $9431, $11,678, respectively. Hospital inpatient costs contributed 70% of total costs for prevalent dementia and accounted for differences between CN and both prevalent and newly discovered dementia. Ambulatory costs accounted for differences between CN and MCI. Age-, sex-, education-adjusted differences reached significance for CN versus newly discovered and prevalent dementia and for MCI versus prevalent dementia. After considering all comorbid diagnoses, between-category differences were reduced (e.g., prevalent dementia minus MCI (from $4842 to $3575); newly discovered dementia minus CN (from $3578 to $711)). Following the exclusion of neuropsychiatric diagnoses from comorbidity adjustment, between-category differences tended to revert to greater differences. CONCLUSIONS: Cost estimates did not differ significantly between CN and MCI. Substantial differences between MCI and prevalent dementia reflected high inpatient costs for dementia and appear partly related to co-occurring mental disorders. Such comparisons can help inform models aimed at identifying where, when, and for which individuals proposed interventions might be cost-effective.

Rethinking guidelines for VTE risk among nursing home residents: a population-based study merging medical record detail with standardized nursing home assessments.

BACKGROUND: Nursing home (NH) residents are at increased risk for both VTE and bleeding from pharmacologic prophylaxis. Construction of prophylaxis guidelines is hampered by NH-specific limitations with VTE case identification and characterization of risk. We addressed these limitations by merging detailed provider-linked Rochester Epidemiology Project (REP) medical records with Centers for Medicare and Medicaid Services Minimum Data Set (MDS) NH assessments. METHODS: This population-based nested case-control study identified all Olmsted County, Minnesota, residents with first-lifetime VTE October 1, 1998, through December 31, 2005, while a resident of an NH (N = 91) and one to two age-, sex-, and calendar year-matched NH non-VTE control subjects. For each NH case without hospitalization 3 months before VTE (n = 23), we additionally identified three to four nonhospitalized NH control subjects. REP and MDS records were reviewed before index date (VTE date for cases; respective REP encounter date for control subjects) for numerous characteristics previously associated with VTE in non-NH populations. Data were modeled using conditional logistic regression. RESULTS: The multivariate model consisting of all cases and control subjects identified only three characteristics independently associated with VTE: respiratory infection vs no infection (OR, 5.9; 95% CI, 2.6-13.1), extensive or total assistance with walking in room (5.6, 2.5-12.6), and general surgery (3.3, 1.0-10.8). In analyses limited to nonhospitalized cases and control subjects, only nonrespiratory infection vs no infection was independently associated with VTE (8.8, 2.7-29.2). CONCLUSIONS: Contrary to previous assumptions, most VTE risk factors identified in non-NH populations do not apply to the NH population. NH residents with infection, substantial mobility limitations, or recent general surgery should be considered potential candidates for VTE prophylaxis.

Complex regional pain syndrome in a young athlete with von Willebrand disease.

A 17-year-old female with type 1 Von Willebrand Disease (vWD) developed left medial calf pain while running track. Over the next 6 months, orthopedic surgery, sports medicine, vascular surgery, and neurology treated her under various working diagnoses; however, the pain, allodynia, coldness, and pale skin color worsened. She was admitted to a tertiary pediatric hospital for intractable pain where PM&R diagnosed her with complex regional pain syndrome (CRPS) type 1, began gabapentin, and initiated an aggressive inpatient rehabilitation program. During her 3 weeks of inpatient rehabilitation, passive range of motion of knee extension improved from 40° from extension to full extension, and ankle dorsiflexion improved from 15° from neutral to a consistent range of motion beyond neutral. Additional outcome measures were distance of ambulation and assistive device usage; from admission to inpatient rehabilitation to 2 months postdischarge, her weight-bearing tolerance progressed from nonweight-bearing to partial weight-bearing, and ambulation improved from 20 feet with a three-point crutch gait to unlimited distances with a four-point crutch gait. This is the first known case of a bleeding disorder as the likely underlying microvascular pathology associated with CRPS, a theory exposed in 2010.

Electromagnetic acoustic imaging.

Electromagnetic acoustic imaging (EMAI) is a new imaging technique that uses long-wavelength RF electromagnetic (EM) waves to induce ultrasound emission. Signal intensity and image contrast have been found to depend on spatially varying electrical conductivity of the medium in addition to conventional acoustic properties. The resultant conductivity- weighted ultrasound data may enhance the diagnostic performance of medical ultrasound in cancer and cardiovascular applications because of the known changes in conductivity of malignancy and blood-filled spaces. EMAI has a potential advantage over other related imaging techniques because it combines the high resolution associated with ultrasound detection with the generation of the ultrasound signals directly related to physiologically important electrical properties of the tissues. Here, we report the theoretical development of EMAI, implementation of a dual-mode EMAI/ultrasound apparatus, and successful demonstrations of EMAI in various phantoms designed to establish feasibility of the approach for eventual medical applications.

Traumatic brain injury in children.

Traumatic Brain Injury (TBI) is a major cause of morbidity and is the leading cause of death and acquired disability in children. It has been referred to as the "silent epidemic" and is a major public health concern with significant long term sequellae. More aggressive management has improved mortality in children. Outcomes depend on injury severity. Multi-disciplinary intervention can help to hasten recovery, improve outcomes, and decrease complications.

Evaluation of a standardized procedure for [corrected] microscopic cell counts [corrected] in body fluids.

A standardized urinalysis and manual microscopic cell counting system was evaluated for its potential to reduce intra- and interoperator variability in urine and cerebrospinal fluid (CSF) cell counts. Replicate aliquots of pooled specimens were submitted blindly to technologists who were instructed to use either the Kova system with the disposable Glasstic slide (Hycor Biomedical, Inc., Garden Grove, CA) or the standard operating procedure of the University of California-Irvine (UCI), which uses plain glass slides for urine sediments and hemacytometers for CSF. The Hycor system provides a mechanical means of obtaining a fixed volume of fluid in which to resuspend the sediment, and fixes the volume of specimen to be microscopically examined by using capillary filling of a chamber containing in-plane counting grids. Ninety aliquots of pooled specimens of each type of body fluid were used to assess the inter- and intraoperator reproducibility of the measurements. The variability of replicate Hycor measurements made on a single specimen by the same or different observers was compared with that predicted by a Poisson distribution. The Hycor methods generally resulted in test statistics that were slightly lower than those obtained with the laboratory standard methods, indicating a trend toward decreasing the effects of various sources of variability. For 15 paired aliquots of each body fluid, tests for systematically higher or lower measurements with the Hycor methods were performed using the Wilcoxon signed-rank test. Also examined was the average difference between the Hycor and current laboratory standard measurements, along with a 95% confidence interval (CI) for the true average difference. Without increasing labor or the requirement for attention to detail, the Hycor method provides slightly better interrater comparisons than the current method used at UCI.

Spurious hypocalcemia after Omniscan- or OptiMARK-enhanced magnetic resonance imaging: an algorithm for minimizing a false-positive laboratory value.

Contrast-enhanced magnetic resonance imaging has become a routine diagnostic imaging procedure. Reports in the literature document that 2 of the 4 available gadolinium-based magnetic resonance imaging contrast agents, gadodiamide (Omniscan) and gadoversetamide (OptiMARK), are less stable and readily undergo dechelation. In vitro, this dechelation can result in interference with the most common laboratory methods used to measure total plasma or serum calcium. The result of total calcium measurement soon after contrast-enhanced magnetic resonance imaging with these interfering contrast agents is a spurious lowering of the total calcium level. This low calcium measurement may result in a value consistent with hypocalcemia and can persist in patients with renal insufficiency and in patients receiving higher doses of contrast agent. Alternatively, a clinically significant elevated calcium level may be overlooked because of the artificially lowered value. Two of the available gadolinium-based contrast agents, gadoteridol (ProHance) and gadopentetate dimeglumine (Magnevist), have not been to shown to interfere with total calcium measurement. A clinical practice algorithm for the laboratorian, the radiologist, and the clinician is presented to minimize the occurrence and consequences of a spuriously lowered total calcium level due to Omniscan- or OptiMARK-enhanced magnetic resonance imaging.