Assessing COVID-19 testing strategies in K-12 schools in underserved populations: study protocol for a cluster-randomized trial.

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021.

Lifestyle Moderates Genetic Risk of Venous Thromboembolism: The ARIC Study.

OBJECTIVE: Venous thromboembolism (VTE) is a common disease that has a genetic basis. Lifestyle factors contribute to risk, but it is unknown whether healthy lifestyle can mitigate the genetic risk. We studied whether greater adherence to the American Heart Association's cardiovascular health metric, Life's Simple 7 (LS7), is associated with lower incidence of VTE in individuals across categories of a genetic risk score (GRS) for VTE. Approach AND RESULTS: We followed 9026 White participants from the ARIC (Atherosclerosis Risk in Communities) Study, a prospective cohort enrolled in 1987 to 1989 until 2015. We tested the joint associations with VTE of a validated VTE GRS comprising 5 well-known gene variants and baseline LS7 categories. There were 466 incident VTE events over 22.8 years. Participants with an optimal LS7 score had a lower incidence of VTE (3.9%) than those with inadequate LS7 (5.7%). Compared with the high GRS and inadequate LS7 group (hazard ratio=1), those with high GRS and optimal LS7 indeed had a reduced hazard ratio of VTE: 0.65 (95% CI, 0.48-0.89). The group with low GRS and optimal LS7 had the lowest hazard ratio of VTE (0.39 [95% CI, 0.25-0.61]). Of the LS7 components, in all GRS groups, the factor most strongly protective for VTE was normal weight. CONCLUSIONS: Among people at low or high genetic risk for VTE, healthier lifestyle factors, particularly normal weight, were associated with a lower incidence of VTE. Further studies should determine the impact of lifestyle changes among patients at high genetic risk of VTE, such as in thrombophilic families.

C-reactive protein and stroke risk in blacks and whites: The REasons for Geographic And Racial Differences in Stroke cohort.

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker used in vascular risk prediction, though with less data in people of color. Blacks have higher stroke incidence and also higher CRP than whites. We studied the association of CRP with ischemic stroke risk in blacks and whites. METHODS: REGARDS, an observational cohort study, recruited and followed 30,239 black and white Americans 45 years and older for ischemic stroke. We calculated hazard ratios and 95% CIs of ischemic stroke by CRP category (<1, 1-3, 3-10, and ≥10 mg/L) adjusted for age, sex and stroke risk factors. RESULTS: There were 292 incident ischemic strokes among blacks and 439 in whites over 6.9 years of follow-up. In whites, the risk was elevated for CRP in the range from 3 to 10 mg/L and even higher for CRP >10 mg/L, whereas in blacks, an association was only seen for CRP >10 mg/L. Considered as a continuous variable, the risk factor-adjusted hazard ratios per SD higher lnCRP were 1.18 (95% CI 1.09-1.28) overall, 1.14 (95% CI 1.00-1.29) in blacks, and 1.22 (95% CI 1.10-1.35) in whites. Spline regression analysis visually confirmed the race difference in the association. CONCLUSIONS: CRP may not be equally useful in stroke risk assessment in blacks and whites. Confirmation, similar study for coronary heart disease, and identification of reasons for these racial differences require further study.

Stopper Movement and Headspace (Air Bubble Size) Limitations for 2.25 mL Prefilled Syringe.

The sterile barrier is one of the most important aspects of the container closure integrity (CCI) for a prefilled syringe (PFS or syringe). This crucial barrier enables the protection of the syringe contents from contamination. The plunger stopper (stopper) is naturally in a stationary position that is controlled by the static friction between the plunger stopper and the syringe barrel wall. When an applied force is greater than the static friction, which is commonly known as the break-loose force, the plunger stopper will move. In such conditions, the stopper movement can further be increased if an air bubble (AB) is introduced between the liquid fill in the syringe and the stopper during the stoppering process. This additional movement can occur when the pressure differential between the gaseous headspace inside the syringe and the external atmosphere is large enough that the force exerted on the stopper exceeds the break-loose force of the syringe. This can occur during altitude or temperature changes incurred during aerial or mountainous transport. This article, therefore, discusses the relationship between stopper movement and initial headspace (air bubble size/ABS) in a 2.25 mL Type I glass syringe using theoretical and empirical approaches. The results showed the maximum initial headspace needed to enable CCI at specified altitudes and plunger stopper movements for the syringe-plunger stopper combination used in the study. Empirical data also indicated that CCI can be maintained for this syringe-plunger stopper combination with up to 9.0 mm initial headspace at altitudes up to 17,000 feet.

Determination of ICH-Q3D Elemental Impurity Leachables in Glass Vials by Inductively Coupled Plasma Mass Spectrometry.

Container closure systems that are used for packaging pharmaceutical products are required to satisfy numerous safety requirements. Maximum permitted limits on the concentrations of numerous toxic elemental impurities that potentially leach from the packaging are one such requirement. The implementation of ICH-Q3D Guideline for Elemental Impurities, in conjunction with the 2018 publication of USP <232> Elemental Impurities-Limits and USP <233> Elemental Impurities-Procedures, requires a critical risk assessment of all container closure systems to evaluate their contribution of certain elemental impurities to the enclosed drug product. ICH-Q3D has established limits for each specific elemental impurity that considers relevant toxicological data and administration route (oral, parenteral, or inhalation) and presents them as permitted daily exposures based on the maximum daily dosage of the final drug product. A study was undertaken to assess the degree of elemental impurity leaching from one type of pharmaceutical glass vial under specific, fixed environmental controls. Multiple buffer systems representing a broad spectrum of possible parenteral drug product formulations were used in the study. Resulting buffer solutions that had been in contact with a single type of glass vial under specific conditions were subsequently analyzed using an inductively coupled plasma mass spectrometry (ICP-MS) method developed and validated specifically for the purpose of quantifying elemental impurity leachables in a variety of parenteral formulations. Results indicated that the degree of elemental impurity leachables imparted by the specific type of glass vial evaluated during this study posed no risk to patient safety, regardless of the drug product buffer formulation. Following this evaluation, the ICP-MS method developed for the determination of elemental impurities leachables has been successfully applied to the assessment of elemental impurities in a number of different biological parenteral drug product formulations currently under development. These data can be leveraged for inclusion in elemental impurities component ICH-Q3D risk assessments to satisfy the container closure system contribution.

Container Closure Integrity of Vial Primary Packaging Systems under Frozen Storage Conditions: A Case Study.

As the complexities of the pharmaceuticals needed to prevail over serious diseases continue to grow, the need for technologies to enable their efficient storage and delivery are as essential as ever. Lately, drugs such as vaccines, proteins, and stem cells are increasingly requiring frozen storage to maintain their efficacies before use. Notably, the advent of cellular therapy products has invariably elevated the need for cryopreservation and frozen storage of cellular starting materials, intermediates, and/or final product. The container closure integrity (CCI)-which is a major requirement for aseptic or sterile packaging systems-at these extremely low temperatures has not been fully understood. For vial-based systems particularly, the commonly used rubber stoppers are expected to lose their elastic properties below their glass transition temperatures, suggesting a potential temporary loss of sealability under frozen storage conditions and posing a risk to CCI. The measurement of the CCI at these conditions such as -80°C is therefore critical; a process that can be very challenging. Previous works had explored the use of Oxygen Headspace Analysis to measure CCI at low temperatures. Here, we present the evaluation of the CCI of rubber-stoppered aluminosilicate glass vials (Valor®) and plastic vials (Crystal Zenith®) using the helium leak CCI test method at -80°C, with correlation to residual seal force (RSF). The results and their implications are then discussed with regard to the suitability of certain packaging components as frozen storage container closure systems.

Prophylactic fresh frozen plasma versus prothrombin complex concentrate for preprocedural management of the coagulopathy of liver disease: A systematic review.

Background: The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known. Objectives: Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease. Methods: We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single-arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion-related complications. Results: A total of 95 articles were identified for full-text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single-arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta-analysis was not possible. Our study found no evidence to favor a specific product over another. Conclusions: Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.

Community Engagement Practices at Research Centers in U.S. Minority Institutions: Priority Populations and Innovative Approaches to Advancing Health Disparities Research.

This paper details U.S. Research Centers in Minority Institutions (RCMI) Community Engagement Cores (CECs): (1) unique and cross-cutting components, focus areas, specific aims, and target populations; and (2) approaches utilized to build or sustain trust towards community participation in research. A mixed-method data collection approach was employed for this cross-sectional study of current or previously funded RCMIs. A total of 18 of the 25 institutions spanning 13 U.S. states and territories participated. CEC specific aims were to support community engaged research (94%); to translate and disseminate research findings (88%); to develop partnerships (82%); and to build capacity around community research (71%). Four open-ended questions, qualitative analysis, and comparison of the categories led to the emergence of two supporting themes: (1) establishing trust between the community-academic collaborators and within the community and (2) building collaborative relationships. An overarching theme, building community together through trust and meaningful collaborations, emerged from the supporting themes and subthemes. The RCMI institutions and their CECs serve as models to circumvent the historical and current challenges to research in communities disproportionately affected by health disparities. Lessons learned from these cores may help other institutions who want to build community trust in and capacities for research that addresses community-related health concerns.

Smoking-related correlates of depressive symptoms in low-income pregnant women.

OBJECTIVES: To investigate smoking-related correlates of depressive symptomatology in low-income pregnant women. METHODS: A cross-sectional survey of 245 pregnant women who smoked prior to pregnancy. RESULTS: Women who had lower self-efficacy for maintaining abstinence both in positive affect/social situations and when experiencing negative affect demonstrated greater depressive symptomatology. Additionally, marijuana use, nicotine dependence, and general confidence in one's ability to quit smoking showed a positive relationship to depression. CONCLUSIONS: Several modifiable factors that can be targeted through behavioral and cognitive behavioral intervention strategies appear to influence the relationship between depression and smoking in low-income pregnant women.

Approaches to learning, need for cognition, and strategic flexibility among university students.

BACKGROUND: Considerable research has described students' deep and surface approaches to learning. Other research has described individuals' self-regulated learning and need for cognition. There is a need for research examining the relationships among these constructs. AIMS: This study explored relationships among approaches to learning (deep, surface), need for cognition, and three types of control of learning (adaptive, inflexible, irresolute). Theory suggested similarities among the deep approach, need for cognition, and adaptive control (aspects of self-regulated learning); and among surface, inflexible, and irresolute control (aspects of an ineffective approach to learning). One-factor and two-factor models were proposed. SAMPLE: Participants were 226 Canadian military college students. METHOD: Participants completed the following questionnaires: the Study Process Questionnaire (Biggs, 1978), the Need for Cognition Scale (Cacioppo & Petty, 1982), and the Strategic Flexibility Questionnaire (Cantwell & Moore, 1996). RESULTS: Confirmatory factor analysis supported the identification of the six scale factors. Second order confirmatory factor analysis indicated three factors representing constructs underlying these factors. CONCLUSIONS: Neither the one- nor two-factor models accounted adequately for the data. Self-regulated learning was defined by measures of the deep approach to learning, need for cognition, and adaptive control of learning. The second factor divided into one factor consisting of irresolute control, the surface approach, and negative need for cognition; and another consisting of inflexible and negative adaptive control. Substantial relationships among scales support the need for further theory development.