Extreme γ' fibrinogen levels in COVID-19 patients.

COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.

Iterative Development of an Interactive Website to Support Shared Decision-Making in Metastatic Breast Cancer.

Recent treatment advances have resulted in significantly increased survival times following metastatic breast cancer (MBC) diagnosis. Novel treatment approaches-and their related side effects-have changed the landscape of MBC treatment decision-making. We developed a prototype of an online educational tool to prepare patients with MBC for shared decision-making with their oncologists. We describe the five phases of tool development: (1) in-depth, semi-structured qualitative interviews and (2) feedback on storyboards of initial content with patients with MBC and oncology providers. This was followed by three phases of iterative feedback with patients in which they responded to (3) initial, non-navigable website content and (4) a beta version of the full website. In the final phase (5), patients newly diagnosed with MBC (N = 6) used the website prototype for 1 week and completed surveys assessing acceptability, feasibility, treatment knowledge, preparation for decision-making, and self-efficacy for decision-making. Participants in Phase 1 characterized a cyclical process of MBC treatment decision-making and identified key information needs. Website content and structure was iteratively developed in Phases 2-4. Most participants in Phase 5 (n = 4) accessed the website 2-5 times. All participants who accessed the website at least once (n = 5) felt they learned new information from the website prototype and would recommend it to others newly-diagnosed with MBC. After using the website prototype, participants reported high preparation and self-efficacy for decision-making. This multiphase, iterative process resulted in a prototype intervention designed to support decision-making for MBC patients.

γ' fibrinogen levels as a biomarker of COVID-19 respiratory disease severity.

Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ' fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO2). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95 % CI 64.8-74.8) mg/dL compared with 36.9 (95 % CI 31.4-42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO2 ≤ 93 %, GPF 75.2 (95 % CI 68.7-81.8) mg/dL), compared to mild/moderate COVID-19 (SpO2 > 93 %, GPF 62.5 (95 % CI 55.0-70.0) mg/dL, p = 0.01, AUC of 0.68, 95 % CI 0.57-0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.

Using Protection Motivation Theory to Predict Intentions for Breast Cancer Risk Management: Intervention Mechanisms from a Randomized Controlled Trial.

The purpose of this study is to evaluate the direct and indirect effects of a web-based, Protection Motivation Theory (PMT)-informed breast cancer education and decision support tool on intentions for risk-reducing medication and breast MRI among high-risk women. Women with ≥ 1.67% 5-year breast cancer risk (N = 995) were randomized to (1) control or (2) the PMT-informed intervention. Six weeks post-intervention, 924 (93% retention) self-reported PMT constructs and behavioral intentions. Bootstrapped mediations evaluated the direct effect of the intervention on behavioral intentions and the mediating role of PMT constructs. There was no direct intervention effect on intentions for risk-reducing medication or MRI (p's ≥ 0.12). There were significant indirect effects on risk-reducing medication intentions via perceived risk, self-efficacy, and response efficacy, and on MRI intentions via perceived risk and response efficacy (p's ≤ 0.04). The PMT-informed intervention effected behavioral intentions via perceived breast cancer risk, self-efficacy, and response efficacy. Future research should extend these findings from intentions to behavior. ClinicalTrials.gov Identifier: NCT03029286 (date of registration: January 24, 2017).

Sharing Lessons From Successes: Long-term Care Facilities That Weathered the Storm of COVID-19 and Staffing Crises.

PURPOSE: To identify leadership styles and staffing strategies in Missouri long-term care (LTC) facilities that stood out among their peers as "positive deviants" with regard to COVID-19 infections and staffing shortages. METHODS: Statewide survey of all LTC facilities to identify exemplar facilities with stable staffing and low rates of COVID-19. Interviews with senior leaders were conducted in 10 facilities in the state to understand the strategies employed that led to these "positive outliers." A result-based educational program was designed to describe their actions and staff reactions. RESULTS: Exemplar leaders used transformational leadership style. Top reasons for their success were as follows: (1) trusting and supportive staff relationships; (2) positive presence and communication; and (3) use of consistent staffing assignments. Strong statewide participation was noted in the educational programs.

Optimizing use of written peer support as a supportive resource in cancer: Focus group insights.

PURPOSE: Cancer survivors frequently describe wanting to learn from others who have had similar diagnoses or treatments (peer support). We conducted focus groups to investigate hematopoietic stem cell transplant survivors' attitudes and preferences regarding accessing written peer support through a website. Although written peer support does not allow for interpersonal interactions with peers, it could increase transplant recipients' access to evidence-based benefits of informational and emotional peer support. METHODS: We conducted four videoconference focus groups with 34 adult transplant survivors who were diverse in their medical and sociodemographic characteristics and geographic location. Discussions were recorded, transcribed, and content analyzed. RESULTS: Many participants reported need for information about transplant beyond what they received from their healthcare providers. Needs varied across participants, as did preferences for characteristics and timing of information optimally provided through peer support. Participants were enthusiastic about the value of written peer support but emphasized that it should be delivered in a way that accommodates variation in transplant experiences, underscores its trustworthiness, and pairs it with useful psychoeducational content. CONCLUSIONS: Findings provide guidance for making written peer support an accessible, supportive resource for transplant survivors. Future research should evaluate personalized online delivery of written peer support paired with psychoeducational content that enhances its benefits. IMPLICATIONS FOR CANCER SURVIVORS: Written peer support delivered online could be a useful, valued resource for transplant survivors.

A Web-based Lifestyle Intervention for Cancer Survivors: Feasibility and Acceptability of SurvivorSHINE.

Assess the feasibility, acceptability, and preliminary efficacy of a healthy lifestyle website, SurvivorSHINE ( www.survivorshine.org ), for cancer survivors using a mixed-methods approach. Formative research included a comprehensive literature review and four focus groups on website preferences with diagnosis-diverse cancer survivors (N = 17). Their feedback informed a web adaptation of a telephone counseling and mailed-print lifestyle intervention previously found effective for cancer survivors. The resulting web-based intervention was examined in a 3-week, single-arm trial among 41 cancer survivors. Assessments of physical activity, diet, body weight, and knowledge related to exercise and diet guidelines for cancer survivors occurred at baseline and 3 weeks later, along with exit interviews. Themes from focus groups indicated cancer survivors' desire for easy-to-use, interactive web-based platforms to access credible diet and exercise information. The study sample was recruited within 12 months, and study retention was high (85.4%). Participants showed significant pre- to post-test improvements in diet and exercise knowledge (t = 5.31, p < .0001) and physical activity (t = 2.40, p = .02). Improvements in body weight and some dietary components (red meat, alcohol) were observed, but did not reach statistical significance. Results support the feasibility and acceptability of SurvivorSHINE. The significant increases in healthy lifestyle knowledge and physical activity found in the current study are promising, but a larger, randomized-controlled trial is needed to determine efficacy.

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations.

Posttraumatic coagulopathy involves disruption of both the coagulation and fibrinolytic pathways secondary to tissue damage, hypotension, and inflammatory upregulation. This phenomenon contributes to delayed complications after traumatic brain injury (TBI), including intracranial hemorrhage progression and systemic disseminated intravascular coagulopathy. Development of an early hyperfibrinolytic state may result in uncontrolled bleeding and is associated with increased mortality in patients with TBI. Although fibrinolytic assays are not routinely performed in the assessment of posttraumatic coagulopathy, circulating biomarkers such as D-dimer and fibrin degradation products have demonstrated potential utility in outcome prediction. Unfortunately, the relatively delayed nature of these tests limits their clinical utility. In contrast, viscoelastic tests are able to provide a rapid global assessment of coagulopathy, although their ability to reliably identify disruptions in the fibrinolytic cascade remains unclear. Limited evidence supports the use of hypertonic saline, cryoprecipitate, and plasma to correct fibrinolytic disruption; however, some studies suggest more harm than benefit. Recently, early use of tranexamic acid in patients with TBI and confirmed hyperfibrinolysis has been proposed as a strategy to further improve clinical outcomes. Moving forward, further delineation of TBI phenotypes and the clinical implications of fibrinolysis based on phenotypic variation is needed. In this review, we summarize the clinical aspects of fibrinolysis in TBI, including diagnosis, treatment, and clinical correlates, with identification of targeted areas for future research efforts.

Parental perspectives on negotiations over diet and physical activity: how do we involve parents in adolescent health interventions?

OBJECTIVE: To identify the ways in which parental involvement can be incorporated into interventions to support adolescent health behaviour change. DESIGN: Data from semi-structured interviews were analysed using inductive thematic analysis. SETTING: Southampton, Hampshire, UK. PARTICIPANTS: A convenience sample of twenty-four parents of adolescents. RESULTS: Parents consider themselves to play an important role in supporting their adolescents to make healthy choices. Parents saw themselves as gatekeepers of the household and as role models to their adolescents but recognised this could be both positive and negative in terms of health behaviours. Parents described the changing dynamics of the relationships they have with their adolescents because of increased adolescent autonomy. Parents stated that these changes altered their level of influence over adolescents' health behaviours. Parents considered it important to promote independence in their adolescents; however, many described this as challenging because they believed their adolescents were likely to make unhealthy decisions if not given guidance. Parents reported difficulty in supporting adolescents in a way that was not viewed as forceful or pressuring. CONCLUSIONS: When designing adolescent health interventions that include parental components, researchers need to be aware of the disconnect between public health recommendations and the everyday reality for adolescents and their parents. Parental involvement in adolescent interventions could be helpful but needs to be done in a manner that is acceptable to both adolescents and parents. The findings of this study may be useful to inform interventions which need to consider the transitions and negotiations which are common in homes containing adolescents.

Pilot Test of Connecting Pregnant Women who Smoke to Short Message Service (SMS) Support Texts for Cessation.

INTRODUCTION: Most pregnant women know that smoking poses serious risks to baby and mother, yet many still smoke. We conducted a large randomized controlled trial and found that an SMS text-delivered program helped about 10% of these women quit smoking. In this paper, we describe the feasibility of disseminating a text-based intervention to pregnant women who smoke. METHODS: We tested dissemination in two ways from prenatal clinics and compared recruitment rates to those found in our large randomized controlled trial. The first method involved "direct texting" where study staff identified women who smoked and sent them a text asking them to text back if they wanted to receive texts to help them quit. The second involved "nurse screening" where clinic staff from county health departments screened women for smoking and asked them to send a text to the system if they wanted to learn more about the program. Our primary outcome was feasibility assessed by the number of women who texted back their baby's due date, which served as "enrolling" in the texting program, which we compared to the recruitment rate we found in our large trial. RESULTS: Over 4 months, we texted 91 women from the academic health system. Of those, 17 texted back and were counted as "enrolled." In the health departments, across the 4 months, 12 women texted the system initially. Of those, 10 were enrolled. This rate was similar to the rate enrolled in the randomized controlled trial. DISCUSSION: Two different methods connected pregnant women who smoke to a texting program. One of these methods can be automated further and have the potential of helping many women quit smoking with minimal effort. Clinical Trial # NCT01995097.

Burns and Scalds Assessment Template: standardising clinical assessment of childhood burns in the emergency department.

OBJECTIVES: The Burns and Scalds Assessment Template (BaSAT) is an evidence-based proforma coproduced by researchers and ED staff with the aim of (1) standardising the assessment of children attending ED with a burn, (2) improving documentation and (3) screening for child maltreatment. This study aimed to test whether the BaSAT improved documentation of clinical, contributory and causal factors of children's burns. METHODS: A retrospective before-and-after study compared the extent to which information was recorded for 37 data fields after the BaSAT was introduced in one paediatric ED. Pre-BaSAT, a convenience sample of 50 patient records of children who had a burn was obtained from the hospital electronic database of 2007. The post-BaSAT sample included 50 randomly selected case notes from 2016/2017 that were part of another research project. Fisher's exact test and Mann-Whitney U tests were conducted to test for statistical significance. RESULTS: Pre-BaSAT, documentation of key data fields was poor. Post-BaSAT, this varied less between patients, and median completeness significantly (p<0.001) increased from 44% (IQR 4%-94%) to 96% (IQR 94%-100%). Information on 'screening for maltreatment, referrals to social care and outcome' was poorly recorded pre-BaSAT (median of 4% completed fields) and showed the greatest overall improvement (to 95%, p<0.001). Documentation of domestic violence at home and child's ethnicity improved significantly (p<0.001) post-BaSAT; however, these were still not recorded in 36% and 56% of cases, respectively. CONCLUSION: Introduction of the BaSAT significantly improved and standardised the key clinical data routinely recorded for children attending ED with a burn.

The Platelet Integrin αIIbß3 Differentially Interacts with Fibrin Versus Fibrinogen.

Fibrinogen binding to the integrin αIIbß3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However,in vivoαIIbß3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogenversusfibrin to αIIbß3-mediated platelet functions are unknown. Here, we compared the interaction of αIIbß3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified αIIbß3. When αIIbß3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with αIIbß3 and a greater binding strength. αIIbß3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen- and fibrin-αIIbß3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants αD97E or αD574E with mutated RGD motifs. Fibrin made from a fibrinogen γ'/γ' variant lacking the γC αIIbß3-binding motif was more reactive with αIIbß3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with αIIbß3 than fibrinogen. Fibrin is also less sensitive to αIIbß3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of αIIbß3 binding activity in the absence of the γC-dodecapeptide and the α-chain RGD sequences suggests that the αIIbß3-binding sites in fibrin are not confined to its known γ-chain and RGD motifs.

Short-Read Whole-Genome Sequencing for Laboratory-Based Surveillance of Bordetella pertussis.

Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.

Recommendation of colorectal cancer testing among primary care patients younger than 50 with elevated risk.

In the era of precision medicine, efforts are needed to identify and tailor screening recommendations among elevated-risk patients. Individuals younger than 50years are an important target population, as they comprise 15% of colorectal (CRC) cases and often present with more advanced disease than their 50+ counterparts. In this large study, 2470 patients ages 25-49 used a tablet-based program that assessed risks, matched risks with screening guidelines, and generated tailored printed guideline-concordant recommendations for patients and their providers. The tablet-based program identified 121 (4.9%) patients with risk factors warranting screening before age 50. Likelihood of risk warranting screening was greater for ages 40-49 than <40years (OR: 2.38), females than males (OR: 1.82), and African Americans (OR: 1.69) and non-Hispanic Whites (OR: 2.89) compared to Hispanics. Most common risk factors were family history of polyps (23.1%), personal history of inflammatory bowel disease (19.8%), and combined family history of CRC+polyps (18.2%). Receipt of guideline-concordant screening within 6months of identification was low, including only 5.3% of those who needed colonoscopy and 13.3% for whom colonoscopy or FIT was recommended. Although elevated-risk patients younger than 50years can be readily identified, more than notification is necessary to facilitate screening participation.

Leading Through Team Building.

Nursing center academy prepares leaders for new regulatory requirements and performance-based health care.

Analysis of Conserved Glutamate and Aspartate Residues in Drosophila Rhodopsin 1 and Their Influence on Spectral Tuning.

The molecular mechanisms that regulate invertebrate visual pigment absorption are poorly understood. Studies of amphioxus Go-opsin have demonstrated that Glu-181 functions as the counterion in this pigment. This finding has led to the proposal that Glu-181 may function as the counterion in other invertebrate visual pigments as well. Here we describe a series of mutagenesis experiments to test this hypothesis and to also test whether other conserved acidic amino acids in Drosophila Rhodopsin 1 (Rh1) may serve as the counterion of this visual pigment. Of the 5 Glu and Asp residues replaced by Gln or Asn in our experiments, none of the mutant pigments shift the absorption of Rh1 by more than 6 nm. In combination with prior studies, these results suggest that the counterion in Drosophila Rh1 may not be located at Glu-181 as in amphioxus, or at Glu-113 as in bovine rhodopsin. Conversely, the extremely low steady state levels of the E194Q mutant pigment (bovine opsin site Glu-181), and the rhabdomere degeneration observed in flies expressing this mutant demonstrate that a negatively charged residue at this position is essential for normal rhodopsin function in vivo. This work also raises the possibility that another residue or physiologic anion may compensate for the missing counterion in the E194Q mutant.

Results from the Solithromycin International Surveillance Program (2014).

Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 µg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 µg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 µg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 µg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 µg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 µg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 µg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 µg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 µg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 µg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 µg/ml), and all isolates were inhibited at MIC values of ≤0.5 µg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication.

In Vitro Activity of Ceftolozane-Tazobactam against Anaerobic Organisms Identified during the ASPECT-cIAI Study.

The in vitro activities of ceftolozane-tazobactam, meropenem, and metronidazole were determined against anaerobic organisms isolated from patients with complicated intraabdominal infections (cIAI) in global phase III studies. Ceftolozane-tazobactam activity was highly variable among different species of the Bacteroides fragilis group, with MIC90 values ranging from 2 to 64 µg/ml. More-potent in vitro activity was observed against selected Gram-positive anaerobic organisms; however, small numbers of isolates were available, and, therefore, the clinical significance of these results is unknown. Variable activity of ceftolozane-tazobactam against anaerobic organisms necessitates use in combination with metronidazole for the treatment of cIAI.

Activity of Fusidic Acid Tested against Staphylococci Isolated from Patients in U.S. Medical Centers in 2014.

Fusidic acid (FA) activity was evaluated against 2,002 clinical staphylococcal isolates collected in U.S. hospitals during 2014. FA (MIC50/90, 0.12/0.12 µg/ml) inhibited 99.8% of Staphylococcus aureus isolates at ≤1 µg/ml. Only four S. aureus isolates displayed FA values of >2 µg/ml (three strains with fusC and one with an L461K substitution in fusA), and they were isolated from patients in four states. In conclusion, FA demonstrated sustained, potent activity against this recent collection of U.S. staphylococci.