Healthy Days at Home Among Older Medicare Beneficiaries With Traumatic Brain Injury Requiring Inpatient Rehabilitation.

OBJECTIVE: The objectives of this study were to characterize and identify correlates of healthy days at home (HDaH) before and after TBI requiring inpatient rehabilitation. Setting: Inpatient hospital, nursing home, and home health services. PARTICIPANTS: Average of n= 631 community-dwelling fee-for-service age 66+ Medicare beneficiaries across 30 replicate samples who were hospitalized for traumatic brain injury (TBI) between 2012 and 2014 and admitted to an inpatient rehabilitation facility (IRF) within 72 hours of hospital discharge. DESIGN: Retrospective study using data from Medicare claims supplemented with data from the National Trauma Databank. MAIN MEASURES: The primary outcome, HDaH, was calculated as time alive not using inpatient hospital, nursing home, and home health services in the year before TBI hospitalization and after IRF discharge. RESULTS: We found HDaH declined from 93.2% in the year before TBI hospitalization to 65.3% in the year after IRF discharge (73.6% among survivors only). Most variability in HDaH was: (1) in the first 3 months after discharge and (2) by discharge disposition, with persons discharged from IRF to another acute hospital having the worst prognosis for utilization and death. In negative binomial regression models, the strongest predictors of HDaH in the year after discharge were rehabilitation Functional Independence Measure mobility score (ß = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score (ß = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors (ß = - 0.37; 95% CI, -0.66 to -0.07). CONCLUSION: In this study, among community-dwelling older adults with TBI, we found a notable decrease in the proportion of time spent alive at home without higher-level care after IRF discharge compared to before TBI. The finding that physical disability and comorbidities were the biggest drivers of healthy days alive in this population suggests that a chronic disease management model is required for older adults with TBI to manage their complex health care needs.

Establishing a plan to improve pediatric patient comfort during PIV insertions and blood specimen collection: a quality improvement effort.

HIGHLIGHTS: Patient comfort during peripheral intravenous (PIV) insertion and specimen collection was increased. The authors extended the contingency plan implemented for PICC insertion to include PIV insertion and specimen collection. The authors met their goals by using quality improvement methodology. Prioritizing patient comfort often requires institutional culture change. BACKGROUND: Needle procedures can cause pain and distress, especially in pediatric patients.1 Retrospective data collected at a freestanding pediatric facility revealed that approximately 30% of pediatric patients were not demonstrating sufficient levels of comfort during peripheral intravenous (PIV) catheter insertion and specimen collection (lab draws) even after successful implementation of comfort measures by the vascular access team (VAT) in an adjacent procedure (eg peripherally inserted central catheter placement). The current quality improvement project was implemented to support adaptation and expansion of previous lessons learned to PIVs and lab draws specifically. DESIGN AND METHODS: The VAT used the Pediatric Sedation State Scale,2 a standardized assessment tool integrated into the electronic medical record, to assess procedural comfort during PIVs and lab draws from February 2021 through April 2023. A total of 24 134 patients aged 0 to 18 years were included in the data collection. Interventions were delivered concurrently and included (1) reeducation/ongoing support for implementation of the Comfort Promise3 measures, (2) the creation and implementation of advanced comfort options, and (3) culture change. AIMS AND OBJECTIVES: The goal of the interventions was to improve the percentage of pediatric patients achieving adequate levels of comfort beginning at 68% in year 1 to 90% in year 2. RESULTS: From February 2021 to April 2023, the VAT team was able to improve procedural comfort scores from 68% to 90% of pediatric patients with adequate comfort for lab draws and/or PIV insertions. CONCLUSIONS: While standard comfort measures are a good first step in pain management during needle procedures, they are not sufficient for every pediatric patient. Nitrous, sedation, and the use of anxiolytics and analgesics can play an important role in reducing pain and anxiety during needle procedures and should be considered for patients not achieving adequate levels of comfort with standard comfort measures.

Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II.

BACKGROUND: Approximately two-thirds of patients with mucopolysaccharidosis II (MPS II) have a severe, neuronopathic phenotype, characterized by somatic, cognitive, and behavioral issues. Current standard of care for the treatment of MPS II is enzyme replacement therapy with intravenous recombinant human iduronate-2-sulfatase (idursulfase). To target cognitive manifestations of MPS II, idursulfase has been formulated for intrathecal administration into the cerebrospinal fluid (idursulfase-IT). In accordance with recommendations for patient-focused drug development, semi-structured interviews were conducted to assess caregiver experiences and observations in a 52-week phase 2/3 trial of idursulfase-IT, in addition to intravenous idursulfase in pediatric patients with neuronopathic MPS II, or a substudy which enrolled patients younger than 3 years old, all of whom received idursulfase-IT. RESULTS: Overall, 46 caregivers providing care for 50 children (mean [range] age 7.9 [3-17] years at interview) took part in a single 60-min exit interview; six of these children had participated in the substudy. Qualitative and quantitative data were obtained demonstrating the burden of MPS II experienced by caregivers and their families. Following participation in the trials, 39 (78%) of the children were reported by their caregivers to have experienced improvements in the symptoms and impact of disease. Of those with improvements, 37 (95%) experienced cognitive improvements and 26 (67%) experienced emotional/behavioral improvements. Overall, 43 children (86%) were rated by caregivers as having moderate or severe symptoms before the trials; after the trials, 28 children (56%) were considered to have mild or no symptoms. For the six children who participated in the substudy, these proportions were 83% and 100%, respectively. Caregivers' qualitative descriptions of trial experiences suggested improvements in children's verbal and non-verbal functioning and spatial and motor skills, as well as a positive impact on family life. CONCLUSIONS: This study revealed caregiver-reported improvements in children's MPS II symptoms and the impact of the disease on patients and their families. There was a trend for cognitive improvement and a reduction in severity of MPS II symptoms. After many years of extensive review and regulatory discussions of idursulfase-IT, the clinical trial data were found to be insufficient to meet the evidentiary standard to support regulatory filings.

Trends in End-of-Life Care and Satisfaction Among Veterans Undergoing Surgery.

OBJECTIVE: To examine trends in end-of-life care services and satisfaction among Veterans undergoing any inpatient surgery. SUMMARY BACKGROUND DATA: The Veterans Health Administration has undergone system-wide transformations to improve end-of-life care yet the impacts on end-of-life care services use and family satisfaction are unknown. METHODS: We performed a retrospective, cross-sectional analysis of Veterans who died within 90 days of undergoing inpatient surgery between 01/2010 and 12/2019. Using the Veterans Affairs (VA) Bereaved Family Survey (BFS), we calculated the rates of palliative care and hospice use and examined satisfaction with end-of-life care. After risk and reliability adjustment for each VA hospital, we then performed multivariable linear regression model to identify factors associated with the greatest change. RESULTS: Our cohort consisted of 155,250 patients with a mean age of 73.6 years (standard deviation 11.6). Over the study period, rates of palliative care consultation and hospice use increased more than two-fold (28.1% to 61.1% and 18.9% to 46.9%, respectively) while the rate of BFS excellent overall care score increased from 56.1% to 64.7%. There was wide variation between hospitals in the absolute change in rates of palliative care consultation, hospice use and BFS excellent overall care scores. Rural location and ACGME accreditation were hospital-level factors associated with the greatest changes. CONCLUSIONS: Among Veterans undergoing inpatient surgery, improvements in satisfaction with end-of-life care paralleled increases in end-of-life care service use. Future work is needed to identify actionable hospital-level characteristics that may reduce heterogeneity between VA hospitals and facilitate targeted interventions to improve end-of-life care.

Multicenter evaluation of financial toxicity and long-term health outcomes after injury.

BACKGROUND: Despite the growing awareness of the negative financial impact of traumatic injury on patients' lives, the association between financial toxicity and long-term health-related quality of life (hrQoL) among trauma survivors remains poorly understood. METHODS: Patients from nine trauma centers participating in a statewide trauma quality collaborative had responses from longitudinal survey data linked to inpatient trauma registry data. Financial toxicity was defined based on patient-reported survey responses regarding medical debt, work or income loss, nonmedical financial strain, and forgone care due to costs. A financial toxicity score ranging from 0 to 4 was calculated. Health-related quality of life was assessed using the EuroQol 5 Domain tool. Multivariable regression models evaluated the association between financial toxicity and hrQoL outcomes while adjusting for patient demographics, injury severity and inpatient treatment intensity, and health systems variables. RESULTS: Among the 403 patients providing 510 completed surveys, rates of individual financial toxicity elements ranged from 21% to 46%, with 65% of patients experiencing at least one element of financial toxicity. Patients with any financial toxicity had worse summary measures of hrQoL and higher rates of problems in all five EuroQol 5 Domain domains ( p < 0.05 for all). Younger age, lower household income, lack of insurance, more comorbidities, discharge to a facility, and air ambulance transportation were independently associated with higher odds of financial toxicity ( p < 0.05 for all). Injury traits and inpatient treatment intensity were not independently associated with financial toxicity. CONCLUSION: A majority of trauma survivors in this study experienced some level of financial toxicity, which was independently associated with worse risk-adjusted health outcomes across all hrQoL measures. Risk factors for financial toxicity are not related to injury severity or treatment intensity but rather to sociodemographic variables and measures of prehospital and posthospital health care resource utilization. Targeted interventions and policies are needed to address financial toxicity and ensure optimal recovery for trauma survivors. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Midwifery Practice Leaders' Experiences of Practice Changes Early in the COVID-19 Pandemic: A Qualitative Exploration.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic generated considerable upheaval in all sectors of the US health care system, including maternity care. We focused this inquiry on midwifery practice leaders' experiences and perspectives on changes that occurred in their practices early in the pandemic. METHODS: This was a qualitative descriptive study using thematic analysis. The data were responses to an open-ended question in a survey of pandemic-related employment and clinical practice changes. Findings are presented from a constructivist perspective, describing the experiences and perspectives of a group of US midwifery practice leaders during the initial phase of the COVID-19 pandemic. RESULTS: Two main themes emerged from the analysis: demands on midwives and driving forces. Demands on midwives were 3-fold: clients' needs, modification of care, and midwives' needs. These encompassed the psychological, physical, and emotional toll that caring for women during the pandemic placed on midwives. Driving forces were those entities that spurred and directed change and included regulations, institutions, financial logistics, and team dynamics. Survey respondents in community (home and birth center) practices reported substantial increases in inquiries and client volume, and many respondents expressed concern about withdrawal of students from clinical placements. DISCUSSION: Midwifery practices experienced profound changes in their work environments during the COVID-19 pandemic, with both positive and negative characteristics. These challenges in providing birth care were similar to those reported in other countries. Results indicated existing guidance for maternity care during emergencies did not meet clients' needs. Coordinated planning for maternity care in future prolonged health emergencies should incorporate best practices and include midwives in the process.

A Research Protocol to Study the Priming Effects of Breathing Low Oxygen on Enhancing Training-Related Gains in Walking Function for Persons With Spinal Cord Injury: The BO2ST Trial.

Brief episodes of low oxygen breathing (therapeutic acute intermittent hypoxia; tAIH) may serve as an effective plasticity-promoting primer to enhance the effects of transcutaneous spinal stimulation-enhanced walking therapy (WALKtSTIM) in persons with chronic (>1 year) spinal cord injury (SCI). Pre-clinical studies in rodents with SCI show that tAIH and WALKtSTIM therapies harness complementary mechanisms of plasticity to maximize walking recovery. Here, we present a multi-site clinical trial protocol designed to examine the influence of tAIH + WALKtSTIM on walking recovery in persons with chronic SCI. We hypothesize that daily (eight sessions, 2 weeks) tAIH + WALKtSTIM will elicit faster, more persistent improvements in walking recovery than either treatment alone. To test our hypothesis, we are conducting a placebo-controlled clinical trial on 60 SCI participants who randomly receive one of three interventions: tAIH + WALKtSTIM; Placebo + WALKtSTIM; and tAIH + WALKtSHAM. Participants receive daily tAIH (fifteen 90-sec episodes at 10% O2 with 60-sec intervals at 21% O2) or daily placebo (fifteen 90-sec episodes at 21% O2 with 60-sec intervals at 21% O2) before a 45-min session of WALKtSTIM or WALKtSHAM. Our primary outcome measures assess walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up and Go Test). For safety, we also measure pain levels, spasticity, sleep behavior, cognition, and rates of systemic hypertension and autonomic dysreflexia. Assessments occur before, during, and after sessions, as well as at 1, 4, and 8 weeks post-intervention. Results from this study extend our understanding of the functional benefits of tAIH priming by investigating its capacity to boost the neuromodulatory effects of transcutaneous spinal stimulation on restoring walking after SCI. Given that there is no known cure for SCI and no single treatment is sufficient to overcome walking deficits, there is a critical need for combinatorial treatments that accelerate and anchor walking gains in persons with lifelong SCI. Trial Registration: ClinicalTrials.gov, NCT05563103.

Differential cell motion: A mathematical model of anterior posterior sorting.

Here, we investigate how a subpopulation of cells can move through an aggregate of cells. Using a stochastic force-based model of Dictyostelium discoideum when the population is forming a slug, we simulate different strategies for prestalk cells to reliably move to the front of the slug while omitting interaction with the substrate thus ignoring the overall motion of the slug. Of the mechanisms that we simulated, prestalk cells being more directed is the best strategy followed by increased asymmetric motive forces for prestalk cells. The lifetime of the cell adhesion molecules, while not enough to produce differential motion, did modulate the results of the strategies employed. Finally, understanding and simulating the appropriate boundary conditions are essential to correctly predict the motion.

Heatstroke on the Rise: A Guide to Implementing Tarp-Assisted Cooling With Oscillation (TACO) in the Emergency Department.

Heat-related illnesses, namely, heatstroke is on the rise and is a public health concern nationally and internationally. Heatstroke is generally considered to be a core body temperature greater than 40 °C (104 °F) with dry, hot skin, and central nervous system manifestations. Heatstroke is characterized by a systemic inflammatory response that leads to multiple-organ dysfunction and ultimately death if not treated in a timely manner. Rapid recognition and cooling are imperative, as mortality is high, especially in the elderly. There are many cooling methods that have been studied that include cold-water immersion, tarp-assisted cooling with oscillation (TACO), evaporative cooling (misting/fanning), commercial ice packs, cooling vests and jackets, cold showers, and ice sheets. Although cold-water immersion is the fastest method for cooling, it is not usually feasible in an emergency department (ED). TACO is the most feasible and effective cooling method for EDs. It is vital that EDs have a specific plan in place before implementing TACO, as it requires 30-40 gallons of ice water, a tarp or waterproof sheet, core temperature monitoring, and an ample number of ED staff members to oscillate the water over the patient. Further research is needed to study TACO in the ED setting. As the incidence of heatstroke is expected to increase in the coming years, EDs must have a plan in place to rapidly recognize and treat patients with heatstroke so that patients will have improved outcomes and reduced mortality.

Increasing airway obstruction through life following bronchopulmonary dysplasia: a meta-analysis.

Background: Few studies exist investigating lung function trajectories of those born preterm; however growing evidence suggests some individuals experience increasing airway obstruction throughout life. Here we use the studies identified in a recent systematic review to provide the first meta-analysis investigating the impact of preterm birth on airway obstruction measured by the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. Methods: Cohorts were included for analysis if they reported FEV1/FVC in survivors of preterm birth (<37 weeks' gestation) and control populations born at term. Meta-analysis was performed using a random effect model, expressed as standardised mean difference (SMD). Meta-regression was conducted using age and birth year as moderators. Results: 55 cohorts were eligible, 35 of which defined groups with bronchopulmonary dysplasia (BPD). Compared to control populations born at term, lower values of FEV1/FVC were seen in all individuals born preterm (SMD -0.56), with greater differences seen in those with BPD (SMD -0.87) than those without BPD (SMD -0.45). Meta-regression identified age as a significant predictor of FEV1/FVC in those with BPD with the FEV1/FVC ratio moving -0.04 sds away from the term control population for every year of increased age. Conclusions: Survivors of preterm birth have significantly increased airway obstruction compared to those born at term with larger differences in those with BPD. Increased age is associated with a decline in FEV1/FVC values suggesting increased airway obstruction over the life course.

Developing multidimensional participation profiles after traumatic brain injury: a TBI model systems study.

Purpose. To characterize societal participation profiles after moderate-severe traumatic brain injury (TBI) along objective (Frequency) and subjective (Satisfaction, Importance, Enfranchisement) dimensions.Materials and Methods. We conducted secondary analyses of a TBI Model Systems sub-study (N = 408). Multiaxial assessment of participation included the Participation Assessment with Recombined Tools-Objective and -Subjective questionnaires (Participation Frequency and Importance/Satisfaction, respectively) and the Enfranchisement Scale. Participants provided responses via telephone interview 1-15 years post-injury. Multidimensional participation profiles (classes) were extracted using latent profile analysis.Results. A 4-class solution was identified as providing maximal statistical separation between profiles and being clinically meaningful based on profile demographic features. One profile group (48.5% of the sample) exhibited the "best" participation profile (High Frequency, Satisfaction, Importance, and Enfranchisement) and was also the most advantaged according to socioeconomic indicators. Other profile groups showed appreciable heterogeneity across participation dimensions. Age, race/ethnicity, education level, ability to drive, and urbanicity were features that varied between profiles.Conclusions. Societal participation is a critical, but inherently complex, TBI outcome that may not be adequately captured by a single index. Our data underscore the importance of a multidimensional approach to participation assessment and interpretation using profiles. The use of participation profiles may promote precision health interventions for community integration.Implications for RehabilitationOur study found unidimensional measures of societal participation in traumatic brain injury (TBI) populations that focus exclusively on frequency indicators may be overly simplistic and miss key subjective components of participationTaking a multidimensional perspective, we documented four meaningfully distinct participation subgroups (including both objective and subjective dimensions of societal participation) within the TBI rehabilitation populationMultidimensional profiles of participation may be used to group individuals with TBI into target groups for intervention (e.g., deeper goal assessment for individuals who do not rate standard participation activities as important, but also do not participate and do not feel enfranchised).

What is the relationship between photosensitizing drugs and skin cancer?

ABSTRACT: Many medications are associated with phototoxicity or photoallergy, the two types of photosensitivity. Recently, a warning related to increased skin cancer risk was added to the labeling of the popular diuretic hydrochlorothiazide. This article reviews some photosensitizing medications and describes patient education on preventing and recognizing photosensitivity reactions and skin cancer.

Recurrence of Symptoms Following Cryptococcal Meningitis: Characterizing a Diagnostic Conundrum With Multiple Etiologies.

BACKGROUND: Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence. METHODS: We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate. RESULTS: 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/µL; IQR: 9-76) and lower CSF white blood cell (WBC; 4 cells/µL; IQR: 4-85) counts than paradoxical IRIS (CD4: 78 cells/µL; IQR: 47-142; WBC: 45 cells/µL; IQR: 8-128). Among those with CSF WBC <5 cells/µL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/µL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS. CONCLUSIONS: Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results. CLINICAL TRIALS REGISTRATION: NCT01802385.

Successful Community Discharge Among Older Adults With Traumatic Brain Injury Admitted to Inpatient Rehabilitation Facilities.

Objective: To identify admission characteristics that predict a successful community discharge from an inpatient rehabilitation facility (IRF) among older adults with traumatic brain injury (TBI). Design: In a retrospective cohort study, we leveraged probabilistically linked Medicare Administrative, IRF-Patient Assessment Instrument, and National Trauma Data Bank data to build a parsimonious logistic model to identify characteristics associated with successful discharge. Multiple imputation methods were used to estimate effects across linked datasets to account for potential data linkage errors. Setting: Inpatient Rehabilitation Facilities in the U.S. Participants: The sample included a mean of 1060 community-dwelling adults aged 66 years and older across 30 linked datasets (N=1060). All were hospitalized after TBI between 2011 and 2015 and then admitted to an IRF. The mean age of the sample was 79.7 years, and 44.3% of the sample was women. Interventions: Not applicable. Main Outcome Measures: Successful discharge home. Results: Overall, 64.6% of the sample was successfully discharged home. A logistic model including 4 predictor variables: Functional Independence Measure motor (FIM-M) and cognitive (FIM-C) scores, pre-injury chronic conditions, and pre-injury living arrangement, that were significantly associated with successful discharge, resulted in acceptable discrimination (area under the curve: 0.76, 95% confidence interval [CI]: 0.72-0.81). Higher scores on the FIM-M (odds ratio [OR]:1.07, 95% CI: 1.05-1.09) and FIM-C (OR: 1.05, 95% CI: 1.02-1.08) were associated with greater odds of successful discharge, whereas living alone vs with others (OR: 0.46, 95% CI: 0.30-0.71) and a greater number of chronic conditions (OR: 0.94, 95% CI: 0.90-0.99) were associated with lower odds of successful discharge. Conclusions: The results provide a parsimonious model for predicting successful discharge among older adults admitted to an IRF after a TBI-related hospitalization and provide clinically useful information to inform discharge planning.

Conceptualization of Participation: A Qualitative Synthesis of Brain Injury Stakeholder Perspectives.

Background: The return to participation in meaningful life roles for persons with acquired brain injury (pwABI) is a goal shared by pwABI, their families, clinicians, and researchers. Synthesizing how pwABI define participation will help to identify the aspects of participation important to pwABI and can inform a person-centered approach to participation outcome assessment. To-date, the qualitative synthesis approach has been used to explore facilitators and barriers of participation post-stroke, and views about participation among individuals with stroke in the UK. Objectives: This paper's objectives are to (1) conduct a scoping review of qualitative literature that defines and characterizes participation from the perspective of pwABI of any type, (2) synthesize how pwABI define and categorize participation, and (3) link the themes identified in the qualitative synthesis to the International Classification of Functioning, Disability, and Health (ICF) using standardized linking rules to enhance the comparability of our findings to other types of health information, including standardized outcome measures. Methods: We completed a scoping review of qualitative literature. Our search included PubMed, APA PsychInfo, CINAHL, and Embase databases and included articles that (1) had qualitative methodology, (2) had a sample ≥50% pwABI, (3) had aims or research questions related to the meaning, definition, perception, or broader experience of participation, and (4) were in English. Qualitative findings were synthesized using Thomas and Harden's methodology and resultant themes were linked to ICF codes. Results: The search identified 2,670 articles with 2,580 articles excluded during initial screening. The remaining 90 article abstracts were screened, and 6 articles met the full inclusion criteria for the qualitative synthesis. Four analytical themes emerged: (1) Essential Elements of Participation (2) How pwABI Approach Participation, (3) Where pwABI Participate, and (4) Outcomes of Participation. Each overarching theme included multiple descriptive themes. Conclusion: In this paper, we identified themes that illustrate key components of participation to pwABI. Our results provide insight into the complex perspectives about participation among pwABI and illustrate aspects of participation that should hold elevated importance for clinicians and researchers supporting participation of pwABI.

Using Fluorescence Recovery After Photobleaching data to uncover filament dynamics.

Fluorescence Recovery After Photobleaching (FRAP) has been extensively used to understand molecular dynamics in cells. This technique when applied to soluble, globular molecules driven by diffusion is easily interpreted and well understood. However, the classical methods of analysis cannot be applied to anisotropic structures subjected to directed transport, such as cytoskeletal filaments or elongated organelles transported along microtubule tracks. A new mathematical approach is needed to analyze FRAP data in this context and determine what information can be obtain from such experiments. To address these questions, we analyze fluorescence intensity profile curves after photobleaching of fluorescently labelled intermediate filaments anterogradely transported along microtubules. We apply the analysis to intermediate filament data to determine information about the filament motion. Our analysis consists of deriving equations for fluorescence intensity profiles and developing a mathematical model for the motion of filaments and simulating the model. Two closed forms for profile curves were derived, one for filaments of constant length and one for filaments with constant velocity, and three types of simulation were carried out. In the first type of simulation, the filaments have random velocities which are constant for the duration of the simulation. In the second type, filaments have random velocities which instantaneously change at random times. In the third type, filaments have random velocities and exhibit pausing between velocity changes. Our analysis shows: the most important distribution governing the shape of the intensity profile curves obtained from filaments is the distribution of the filament velocity. Furthermore, filament length which is constant during the experiment, had little impact on intensity profile curves. Finally, gamma distributions for the filament velocity with pauses give the best fit to asymmetric fluorescence intensity profiles of intermediate filaments observed in FRAP experiments performed in polarized migrating astrocytes. Our analysis also shows that the majority of filaments are stationary. Overall, our data give new insight into the regulation of intermediate filament dynamics during cell migration.

Development of a novel patient-reported outcome measure to assess signs and symptoms of COVID-19.

BACKGROUND: Given the urgent need for vaccines and treatments for coronavirus disease 2019 (COVID-19), the Symptoms of Infection with Coronavirus-19 (SIC), a comprehensive, patient-reported outcome (PRO) measure of signs and symptoms associated with COVID-19, was developed in full alignment with current US regulatory guidance to support evaluations of vaccines and treatments in development. METHODS: An initial version of the SIC was developed to address concepts identified through a targeted literature review and consultation with experts in infectious diseases and clinicians routinely managing COVID-19 in a hospital setting. A qualitative study was conducted in sites in the United States among 31 participants aged ≥ 18 years who were English-speaking and willing and able to provide informed consent and a self-reported history by telephone or online method. The measure was refined based on additional feedback from the clinicians and three iterative rounds of combined concept elicitation and cognitive debriefing interviews conducted with patients, caregivers, and healthy volunteers. RESULTS: Among 39 scientific articles identified in the literature review, 35 COVID-19 signs and symptoms were reported and confirmed during interviews with clinicians, patients, and caregivers. Patients and healthy participants suggested changes for refining the draft SIC to ensure consistent interpretation and endorsed both the 24-h recall period and use of an 11-point numeric rating scale (NRS) for capturing change in symptom severity. The final version of the SIC captures the daily presence or absence of 30 symptoms and a rating of severity for 25 of the 30 symptoms using an NRS for those symptoms reported as present. CONCLUSIONS: The SIC comprehensively addresses observations described in the literature, by clinicians, and by patients, and captures patients' experiences with COVID-19 in a manner that minimizes complexity and facilitates completion for both patients and healthy volunteers. This measure is thus appropriate for use in clinical trials of both therapeutics and vaccines for COVID-19.