Quantification of Biopharmaceutically Relevant Nonionic Surfactant Excipients Using Benchtop qNMR.

Nonionic surfactant excipients (NISEs) are commonly added to biologics formulations to mitigate the effects of stress incurred by the active biotherapeutic during manufacturing, transport, and storage. During manufacturing, NISEs are added by dilution of a stock solution directly into a protein formulation, and their accurate addition is critical in maintaining the quality and integrity of the drug product and thus ensuring patient safety. This is especially true for the common NISEs, polysorbates 20 and 80 (PS20 and PS80, respectively) and poloxamer 188 (P188). With the increasing diversity of biologic modalities within modern pharmaceutical pipelines, there is thus a critical need to develop and deploy convenient and user-accessible analytical techniques that can rapidly and reliably quantify these NISEs under biopharmaceutically relevant conditions. We thus pursued 60 MHz benchtop quantitative NMR (qNMR) as a nondestructive and user-friendly analytical technique for the quantification of PS20, PS80, and P188 under such conditions. We demonstrated the ability of benchtop qNMR (1) to quantify simulated PS20, PS80, and P188 stock solutions representative of those used during the drug substance (DS) formulation step in biomanufacturing and (2) to quantify these NISEs at and below their target concentrations (≤0.025% w/v) directly in biologics formulations containing histidine, sucrose, and one of three biotherapeutic modalities (monoclonal antibody, antibody-drug conjugate, and Fc-fusion protein). Our results demonstrate that benchtop qNMR offers a fit-for-purpose, reliable, user-friendly, and green analytical route by which NISE of interest to the biopharmaceutical industry may be readily and reliably quantified. We conclude that benchtop qNMR has the potential to be applied to other excipient formulation components in the presence of various biological modalities as well as the potential for routine integration within analytical and QC laboratories across pharmaceutical development and manufacturing sites.

Clinical and socioeconomic predictors of shunt malfunction in the pediatric emergency department.

OBJECTIVE: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction. METHODS: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders. RESULTS: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision. CONCLUSIONS: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.

Clinically Asymptomatic Hemorrhagic Conversion Is Associated with Need for Inpatient Rehabilitation After Mechanical Thrombectomy for Anterior Circulation Ischemic Stroke.

BACKGROUND: Hemorrhagic conversion (HC) is a known complication after acute ischemic stroke (AIS) in patients undergoing mechanical thrombectomy (MT). Although symptomatic HC has been shown to lead to poor neurologic outcomes, the effect of asymptomatic HC (aHC) is unclear. This study aims to identify predictors of aHC and to determine the short-term outcomes. METHODS: This is a single-institution retrospective study of patients with anterior circulation stroke (AIS) who underwent MT between January 2016 and September 2022. Radiographic HC was identified on postoperative imaging. Asymptomatic hemorrhage was defined as no acute neurologic decline attributable to imaging findings. Baseline characteristics, technical aspects, and outcomes were compared between aHC and no-HC groups. Logistic regression and multivariate analysis were performed. RESULTS: A total of 615 patients underwent MT for AIS, of whom 496 met the inclusion criteria. A total of 235 patients (47.4%) had evidence of aHC. Diabetes mellitus (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.06-2.41; P = 0.03), hyperglycemia (OR, 1.01; 95% CI, 1.00-1.01; P = 0.002), greater number of passes (OR, 1.14; 95% CI, 1.00-1.31; P = 0.05), and longer time to reperfusion (OR, 1.02; 95% CI, 1.00-1.05; P = 0.05) were associated with aHC. Patients with aHC were significantly more likely to require rehabilitation, whereas those without HC were more likely to be discharged home (P < 0.001). There were no significant differences in long-term outcomes. CONCLUSIONS: HC occurred in up to half of patients who underwent MT for AIS, most of whom were clinically asymptomatic. Despite clinical stability, aHC was significantly associated with a greater need for inpatient rehabilitation. Predictors of aHC included hyperglycemia and a longer time to reperfusion.

Demographic Characteristics Associated With Intentions to Receive the 2023-2024 COVID-19 Vaccine.

INTRODUCTION: The U.S. Food and Drug Administration approved the updated 2023-2024 COVID-19 vaccines by Pfizer-BioNTech and Moderna on September 11, 2023. Despite the Centers for Disease Control and Prevention's recommendation that everyone aged ≥6 years receive the updated COVID-19 vaccine, the general public's intentions to receive the new 2023-2024 vaccine are unknown. METHODS: Intentions to receive the new COVID-19 vaccine and the demographic predictors of those intentions were assessed from a survey of adult residents, aged ≥18 years, of Los Angeles County, California conducted in October 2023. RESULTS: Of the 1,090 participants, 701 (64.3%) indicated they were planning on receiving the new COVID-19 vaccine, 217 (19.9%) responded no, and 172 (15.8%) were unsure. Male gender (versus female); age groups of 50-64 and ≥65 years (versus 18-29 years); and ≥$100,000 household income (versus ≤$49,999) were associated with higher odds of reporting yes than reporting no regarding their vaccination intentions. Asian and Hispanic race/ethnicity (versus Non-Hispanic White) were associated with higher odds of indicating not sure than the odds of indicating no vaccination intentions. A significantly higher proportion of not-sure respondents reported "I plan to wait and see if it is safe and may get it later", whereas a significantly higher proportion of no respondents reported "I don't believe I need a COVID-19 vaccine booster" and "I don't trust COVID-19 vaccines." CONCLUSIONS: This study demonstrates demographic differences in attitudes toward COVID-19 vaccination intentions and highlights the importance of promotional messages and initiatives that target more hesitant populations. These messages should address possible side effects and vaccine safety.

A Systematic Review of Tear Vascular Endothelial Growth Factor and External Eye Diseases.

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case-control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions.

The Shunt Valve Recession Technique as a Neuroplastic Surgery Adjunct in Complex and High-Risk Shunt Revisions: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: Ventricular shunting is one of the most common procedures in neurosurgery. However, complications and revisions are frequent. Patients requiring multiple revisions often suffer secondary issues with scalp healing over hardware. Many common ventricular shunt valves have an obligate thickness that creates a visible protrusion and can potentially cause local tissue ischemia and breakdown in the setting of repeated surgery. The authors present a simple technique for recessing the shunt valve into the underlying bone to alleviate protrusion in high-risk cases. Three example cases utilizing this technique are presented. METHODS: The skull directly underlying the planned valve site is uniformly recessed with a cutting burr several millimeters as desired while maintaining the inner cortical bone layer. The valve is fixed with standard cranial plating hardware. EXPECTED OUTCOMES: Three patients are reported who underwent shunt valve recession as an adjunct to their shunt revision with neuroplastic surgery assistance. All patients had undergone multiple prior surgeries that had resulted in thin and high-risk fragile scalp. In 1 patient, the prior valve was eroding through the scalp before the described revision. All patients had satisfactory cosmetic outcomes, and there were no revisions in the 2-month follow-up period. DISCUSSION: Complex and high-risk ventricular shunt patients should be considered for shunt valve recession into the bone to reduce wound-related complications and enhance healing. This is a technically simple, safe, and effective technique to include as a neuroplastic adjunct.

Next Level of Care Protocols in Radiology: Improving Patient Access to Care.

OBJECTIVE: To introduce a novel next level of care (NLC) protocol used in our breast imaging practice to bypass additional imaging and image-guided biopsy orders and to examine the impact of NLC on breast biopsy wait times compared with thyroid biopsy wait times, which do not use NLC. METHODS: Our institutional review board deemed this retrospective analysis to be exempt. NLC was implemented for breast imaging in late 2014. Two 6-month periods before and after the COVID-19 shutdown were sampled and compiled. Data were queried from departmental database and electronic health record for all breast and thyroid biopsies during this time. Time to biopsy (TTB) was defined as the number of days from the diagnostic imaging evaluation recommending the biopsy to the completion of the biopsy. To determine the effect of NLC, TTB was compared between breast and thyroid biopsies. RESULTS: Of the 1,114 breast biopsies and 154 thyroid biopsies included, the mean TTB was 9 days (95% confidence interval 8.4-9.3) for breast and 23 days (95% confidence interval 20.5-25.0) for thyroid. There was a 61% reduction in the mean TTB for patients in the breast group compared with patients in the thyroid group. The effect of the NLC was comparable among different races and ethnicities in the breast group, but a significantly higher mean TTB (24% higher, P = .025) was observed for thyroid biopsies in Black patients compared with thyroid biopsies in Hispanic patients. CONCLUSION: NLC protocol facilitates imaging evaluations and reduces the time interval to image-guided biopsies.

Reclassifying historical disasters: From single to multi-hazards.

Multi-hazard events, characterized by the simultaneous, cascading, or cumulative occurrence of multiple natural hazards, pose a significant threat to human lives and assets. This is primarily due to the cumulative and cascading effects arising from the interplay of various natural hazards across space and time. However, their identification is challenging, which is attributable to the complex nature of natural hazard interactions and the limited availability of multi-hazard observations. This study presents an approach for identifying multi-hazard events during the past 123 years (1900-2023) using the EM-DAT global disaster database. Leveraging the 'associated hazard' information in EM-DAT, multi-hazard events are detected and assessed in relation to their frequency, impact on human lives and assets, and reporting trends. The interactions between various combinations of natural hazard pairs are explored, reclassifying them into four categories: preconditioned/triggering, multivariate, temporally compounding, and spatially compounding multi-hazard events. The results show, globally, approximately 19 % of the 16,535 disasters recorded in EM-DAT can be classified as multi-hazard events. However, the multi-hazard events recorded in EM-DAT are disproportionately responsible for nearly 59 % of the estimated global economic losses. Conversely, single hazard events resulted in higher fatalities compared to multi-hazard events. The largest proportion of multi-hazard events are associated with floods, storms, and earthquakes. Landslides emerge as the predominant secondary hazards within multi-hazard pairs, primarily triggered by floods, storms, and earthquakes, with the majority of multi-hazard events exhibiting preconditioned/triggering and multivariate characteristics. There is a higher prevalence of multi-hazard events in Asia and North America, whilst temporal overlaps of multiple hazards predominate in Europe. These results can be used to increase the integration of multi-hazard thinking in risk assessments, emergency management response plans and mitigation policies at both national and international levels.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

Cost-Effectiveness of a Direct-Aspiration First-Pass Technique versus Stent Retriever in Mechanical Thrombectomy.

OBJECTIVE: A direct-aspiration first-pass technique (ADAPT) in mechanical thrombectomy has been described in recent studies as an efficacious strategy compared with using a stent retriever (SR). We sought to evaluate for cost differences of ADAPT technique versus SR as an initial approach. METHODS: We conducted a retrospective analysis of consecutive patients with mechanical thrombectomy at our institution between 2022 and 2023. Patients were grouped into ADAPT with/without SR as a rescue strategy and SR as an initial approach with allowance of concomitant aspiration. Direct cost data (consumables) were obtained. Baseline demographics, stroke metrics, procedure outcomes and cost, and last follow-up outcomes in modified Rankin Scale were compared between 2 groups. RESULTS: Fifty-six patients were included. Thirty-seven (66.1%) underwent ADAPT, with 11 (29.7%) eventually requiring an SR. Mean age was 64.8 years. The average National Institutes of Health Stroke Scale score was 13.2 in the ADAPT group and 14.0 in the SR group (P = 0.68), with a similar proportion of tissue plasminogen activator (P = 0.53), site of occlusion (P = 0.66), and tandem occlusion (P = 0.69) between the groups. Recanalization was achieved in 94.6% of all patients, with an average of 1.9 passes, 89.3% being TICI 2B or above, with no differences between the 2 groups. Significantly lower cost (P < 0.01) was observed in ADAPT ($14,243.4) compared with SR ($19,003.6). Average follow-up duration was 180.2 days, with mortality of 23.2%. At last follow-up, 55.4% remained functionally independent (modified Rankin Scale score <3) with no difference (P = 0.56) between the ADAPT (59.5%) and SR (47.4%) groups. CONCLUSIONS: Outcomes were comparable between the ADAPT and SR groups. ADAPT reduced procedural consumables cost by approximately $5000 (25%), even if stent retrievers were allowed to be used for rescue. Establishing ADPAT as initial approach may bring significant direct cost savings while obtaining similar outcomes.

Proximity to Cannabis Retailers and Recent Cannabis Use among a Diverse Sample of California Adolescents.

Background: As of May 2023, 23 states and Washington, DC have legalized the sale of cannabis for adults aged 21+, and 38 states, three territories, and D.C. have legalized medical cannabis. Exposure to cannabis retailers could increase adolescent cannabis use. Few studies have examined the impact of residential proximity to cannabis retailers on adolescent cannabis use, and previous findings are inconsistent. Methods: This study examined associations between proximity to cannabis retailers and past 30-day cannabis use. Data were from Project Cal Teens, a statewide survey of California adolescents regarding cannabis-related opinions/behaviors (N = 1406, mean age = 15.5 years, 48% female, 38% Hispanic/Latinx, 33% White, 15% Asian/Pacific Islander, 10% Black/African American, 5% Other/Multiracial). Participants were recruited via schools/social media in 2018-2020. Results: For every additional 5 driving miles to the nearest cannabis retailer, the risk of past 30-day cannabis use was reduced by 3.6% [IRR: 0.964; 95% CI: 0.935-0.994]. For every additional 5 miles from a licensed retailer, the risk of past 30-day cannabis use was reduced by 4.3% [IRR: 0.957; 95% CI: 0.926-0.989]. Interaction analyses revealed that among Hispanic/Latinx students, every 5 miles from a licensed retailer was associated with an 11.9% reduction in the risk of past 30-day cannabis use [IRR: 0.881; 95% CI: 0.820-0.945]. Conclusions: As the number of cannabis retailers in the U.S. increases with the continued legalization of adult cannabis use, research examining the effects of these policies on underage use is crucial. Interventions could include enforcement of zoning laws in/near residential areas to reduce accessibility of adolescents to cannabis retailers.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Clinical practice of vitamin D screening and supplementation in pregnancy in Asia-pacific countries: A cross-sectional study.

Background: Vitamin D deficiency is common in pregnant women. There is scarce information in the Asia-Pacific region on the understanding of vitamin D screening and supplementation in pregnancy among health care professionals. Methods: We performed a cross-sectional study among health care professionals who are part of the Integrated Platform for Research in Advancing Metabolic Health outcomes of Women and Children (IPRMAHO) international study group on their understanding and perception of Vitamin D screening and supplementation in pregnancy. The cross-sectional survey comprised 4 main sections: demographics, existing policies, nutrient supplementation in pregnancy and various practices on screening, treatment and perceptions, with a total of 22 questions. A total of 15 responses were obtained from attendees from distinct health facilities across eleven participating Asia-Pacific countries. Results: Majority of the surveyed hospitals (11/15, 78.6 %) did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy. More than half of respondents were (9/14, 64.3 %) were unsure of the percentage of women seen with Vitamin D deficiencies each year and were unsure of Vitamin D dosage prescribed to pregnant women with (8/15, 53.3 %) or without (6/14, 42.9 %) Vitamin D deficiency. Vitamin D was rarely prescribed in pregnancy when compared to other nutrient supplements such as folic acid and iron. Majority of respondents (9/11, 72.7 %) indicated that their hospital did not screen for Vitamin D deficiencies in pregnancy, even amongst high risk pregnant women. Nevertheless, majority of respondents indicated a need (12/15, 80.0 %) for a guideline or consensus regarding Vitamin D screening and supplementation in pregnancy. Conclusion: While majority of the surveyed hospitals did not have a national policy or regional guideline regarding Vitamin D screening and supplementation in pregnancy, majority of respondents indicated a need for the policy or guideline. There were varying clinical knowledge gaps and different perceptions on Vitamin D screening and supplementation in pregnancy among healthcare professionals.

Metabolic shift toward ketosis in asocial cavefish increases social-like affinity.

BACKGROUND: Social affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated. RESULTS: In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After 1 month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with exogenous ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity. CONCLUSIONS: Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality.

Characteristics associated with attitudes and behaviors towards mask wearing during the COVID-19 pandemic: The Trojan Pandemic Response Initiative.

BACKGROUND: Attitudes and behaviors towards mask wearing may influence the ability to reduce transmission of COVID-19 and other diseases. METHODS: University students, staff, and faculty (N = 9653) responded to an email invitation to complete electronic surveys (November 2021 and April 2022). Surveys included 19 items measuring attitudes and behaviors towards mask wearing from the Understanding America Study. Linear mixed models including variables for sex, age group, division, race and ethnicity, political affiliation, and history of COVID-19, were used to estimate the mean difference of the mean score for attitudes and behavior between Time 1 (November 2021) and Time 2 (April 2022). RESULTS: Participants were mostly female (62.1%), students (70.6%), White (39.5%) and Asian (34.7%). More than half identified their political affiliation as Democrat (65.5%). Characteristic variable-by-time interactions for difference in mean mask attitude scores difference were significant at Time 1 (T1) and Time 2 (T2) between Black and White participants (B = 0.18 (0.05), 95% CI: 0.07, 0.28, p = 0.001), Asian and White participants (B = 0.07 (0.02), 95% CI: 0.03-0.12, p = 0.001), participants with self-reported history of COVID-19 and no history of COVID-19 (B= -0.13 (0.02), 95% CI: -0.07, -0.18, p < 0.0001), females and males (B = 0.07 (0.02), 95% CI: 0.03, 0.11, p = 0.001), Republicans and Democrats (B= -0.18 (0.04), 95%CI: -0.26, -0.10, p < 0.0001) and Independents and Democrats (B= -0.10 (0.03), 95%CI: -0.15, -0.05, p < 0.0001). Mean difference in mean scores for mask behaviors at Time and Time 2 were significant between participants with COVID-19 and participants who did not have COVID-19 (B= -0.12 (0.04), 95% CI: -0.19, -0.04, p = 0.004), students compared to faculty and staff (B=-0.22 (0.05), -0.32, -0.12, p < 0.0001), between Republicans and Democrats (B-= -0.16 (0.07), 95% CI: -0.28, -0.03, p = 0.020, and between Independents and Democrats (B=-0.08 (0.04), 95% CI: -0.16, -0.002, p = 0.04). CONCLUSION: Race and ethnicity, political affiliation, and division may affect attitudes and behaviors in mask wearing. Further investigation into how characteristics influence public health measures such as mask wearing is needed to contain the spread of the COVID-19 virus, other infectious diseases, and future pandemics.

Risk factors for failure to achieve minimal clinically important difference following cervical disc replacement.

BACKGROUND CONTEXT: While cervical disc replacement (CDR) has been emerging as a reliable and efficacious treatment option for degenerative cervical spine pathology, not all patients undergoing CDR will achieve minimal clinically important difference (MCID) in patient-reported outcome measures (PROMs) postoperatively-risk factors for failure to achieve MCID in PROMs following CDR have not been established. PURPOSE: To identify risk factors for failure to achieve MCID in Neck Disability Index (NDI, Visual Analog Scale (VAS) neck and arm following primary 1- or 2-level CDRs in the early and late postoperative periods. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Patients who had undergone primary 1- or 2-level CDR for the treatment of degenerative cervical pathology at a single institution with a minimum follow-up of 6 weeks between 2017 and 2022. OUTCOME MEASURES: Patient-reported outcomes: Neck disability index (NDI), Visual analog scale (VAS) neck and arm, MCID. METHODS: Minimal clinically important difference achievement rates for NDI, VAS-Neck, and VAS-Arm within early (within 3 months) and late (6 months to 2 years) postoperative periods were assessed based on previously established thresholds. Multivariate logistic regressions were performed for each PROM and evaluation period, with failure to achieve MCID assigned as the outcome variable, to establish models to identify risk factors for failure to achieve MCID and predictors for achievement of MCID. Predictor variables included in the analyses featured demographics, comorbidities, diagnoses/symptoms, and perioperative characteristics. RESULTS: A total of 154 patients met the inclusion criteria. The majority of patients achieved MCID for NDI, VAS-Neck, and VAS-Arm for both early and late postoperative periods-79% achieved MCID for at least one of the PROMs in the early postoperative period, while 80% achieved MCID for at least one of the PROMs in the late postoperative period. Predominant neck pain was identified as a risk factor for failure to achieve MCID for NDI in the early (OR: 3.13 [1.10-8.87], p-value: .032) and late (OR: 5.01 [1.31-19.12], p-value: .018) postoperative periods, and VAS-Arm for the late postoperative period (OR: 36.63 [3.78-354.56], p-value: .002). Myelopathy was identified as a risk factor for failure to achieve MCID for VAS-Neck in the early postoperative period (OR: 3.40 [1.08-10.66], p-value: .036). Anxiety was identified as a risk factor for failure to achieve MCID for VAS-Neck in the late postoperative period (OR: 6.51 [1.91-22.18], p-value: .003). CDR at levels C5C7 was identified as a risk factor for failure to achieve MCID in NDI for the late postoperative period (OR: 9.74 [1.43-66.34], p-value: .020). CONCLUSIONS: Our study identified several risk factors for failure to achieve MCID in common PROMs following CDR including predominant neck pain, myelopathy, anxiety, and CDR at levels C5-C7. These findings may help inform the approach to counseling patients on outcomes of CDR as the evidence suggests that those with the risk factors above may not improve as reliably after CDR.

Large variation in radiation dose for routine abdomen CT: reasons for excess and easy tips for reduction.

OBJECTIVE: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT. METHODS: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, contributed by 95 hospitals and imaging facilities. Grouping exams into deciles by, first, patient size, and second, size-adjusted dose length product (DLP), we summarized dose and technical parameters and estimated which parameters contributed most to between-protocols dose variation. Lastly, we modeled the total population dose if all protocols with mean size-adjusted DLP above 433 or 645 mGy-cm were reduced to these thresholds. RESULTS: A total of 748,846 CTs were performed using 1033 unique protocols. When sorted by patient size, patients with larger abdominal diameters had increased dose and effective mAs (milliampere seconds), even after adjusting for patient size. When sorted by size-adjusted dose, patients in the highest versus the lowest decile in size-adjusted DLP received 6.4 times the average dose (1680 vs 265 mGy-cm) even though diameter was no different (312 vs 309 mm). Effective mAs was 2.1-fold higher, unadjusted CTDIvol 2.9-fold, and phase 2.5-fold for patients in the highest versus lowest size-adjusted DLP decile. There was virtually no change in kV (kilovolt). Automatic exposure control was widely used to modulate mAs, whereas kV modulation was rare. Phase was the strongest driver of between-protocols variation. Broad adoption of optimized protocols could result in total population dose reductions of 18.6-40%. CONCLUSION: There are large variations in radiation doses for routine abdomen CT unrelated to patient size. Modification of kV and single-phase scanning could result in substantial dose reduction. CLINICAL RELEVANCE: Radiation dose-optimization techniques for routine abdomen CT are routinely under-utilized leading to higher doses than needed. Greater modification of technical parameters and number of phases could result in substantial reduction in radiation exposure to patients. KEY POINTS: • Based on an analysis of 748,846 routine abdomen CT scans in adults, radiation doses varied tremendously across patients of the same size and optimization techniques were routinely under-utilized. • The difference in observed dose was due to variation in technical parameters and phase count. Automatic exposure control was commonly used to modify effective mAs, whereas kV was rarely adjusted for patient size. Routine abdomen CT should be performed using a single phase, yet multi-phase was common. • kV modulation by patient size and restriction to a single phase for routine abdomen indications could result in substantial reduction in radiation doses using well-established dose optimization approaches.

An in vitro dynamic bioreactor model for evaluating antimicrobial effectiveness on periodontal polymicrobial biofilms: a proof-of-concept study.

BACKGROUND: The aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque. METHODS: Biofilms from pooled subgingival plaque were grown for 108  hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice-daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction. RESULTS: Following establishment of the oral microcosm biofilms, confocal imaging analysis showed a significant increase in dead bacteria at 8 hours (p = 0.0095), 48 hours (p = 0.0070), 96 hours (p = 0.0140), and 120 hours (p < 0.0001) in the amoxicillin-treated biofilms compared to the control biofilms. Nevertheless, viable bacteria remained in the center of the biofilm at all timepoints. Significant reductions/elimination in Campylobacter rectus, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Peptostreptococcus anaerobius was observed among the amoxicillin-treated biofilms at the 96 and 120 hour timepoints. CONCLUSION: A novel in vitro dynamic model of oral microcosm biofilms was effective in modeling the antimicrobial effect of a pharmacokinetically simulated clinically relevant dose of amoxicillin.