Report of the ISTH registry on pregnancy and COVID-19-associated coagulopathy (COV-PREG-COAG).

Background: Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. Methods: An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. Results: All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Conclusions: Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave.

Primary Care and Community-Based Partnerships to Enhance HPV Vaccine Delivery.

INTRODUCTION/OBJECTIVES: With growing vaccination misinformation and mistrust, strategies to improve vaccination communication across community-based settings are needed. METHODS: The Rural Adolescent Vaccine Enterprise (RAVE), a 5-year (2018-2022) stepped-wedge cluster randomized study, tested a clinic-based practice facilitation intervention designed to improve HPV vaccination. An exploratory aim sought to explore the use of partnerships between primary care clinics and a community partner of their choosing, to implement a social marketing campaign related to HPV immunization. We assessed perceptions about the value and success of the partnership, and barriers and facilitators to its implementation using a 29-item community partner survey, key informant interviews, and field notes from practice facilitators. RESULTS: Of the initial 45 clinics participating in RAVE, 9 were unable to either start or complete the study, and 36 participants (80.0%) were actively engaged. Of these, 16/36 clinics (44.4%) reported establishing successful partnerships, 10 reported attempting to develop partnerships (27.8%), and another 10 reported not developing a partnership (27.8%), which were often caused by the COVID-19 pandemic. The most common partnership was with public health departments at 27.3%. Other partnerships involved libraries, school districts, and local businesses. More than half (63.7%) reported that creating messages regarding getting HPV vaccination was moderately to very challenging. Just under half reported (45.5%) that messaging was hard because of a lack of understanding about the seriousness of diseases caused by HPV, parents being against vaccines because of safety concerns, and religious values that result in a lack of openness to HPV vaccines. Community partners' health priorities changed as a result of RAVE, with 80% prioritizing childhood immunizations as a result of the RAVE partnership. CONCLUSIONS: Community groups want to partner with primary care organizations to serve their patients and populations. More research is needed on how best to bring these groups together.

Challenges in Use of Practice-based Research Networks for a Medical Device Trial to Detect SARS-CoV-2.

INTRODUCTION/OBJECTIVES: Primary care practice-based research networks (PBRNs) participated in a point of care (POC) device study funded by by the National Institutes of Health and led by the University of Massachusetts Chan Medical School (UMass) to speed the development, validation, and commercialization of POC tests to detect SARS-CoV-2. The purposes of this study were to describe the characteristics of participating PBRNs and their respective collaborators in this device trial and describe complications challenging its execution. METHODS: Semi-structured interviews were conducted with lead personnel from participating PBRNs and UMass. RESULTS: Four PBRNs and UMass were invited to participate and 3 PBRNs and UMass participated. This device trial recruited 321 subjects in 6 months; 65 subjects from PBRNs. Each PBRN and the academic medical center site enrolled and recruited subjects differently. Main challenges identified were having adequate clinic personnel to enroll and aid in consent and questionnaire completion, frequently changing inclusion/exclusion criteria, use of the digital electronic data collection platform, and having access to a -80°C freezer to store supplies. DISCUSSION: This trial involved numerous researchers, primary care clinic leaders and staff, and academic center sponsored program staff and attorneys resulting in a resource-intensive endeavor to enroll 65 subjects in the real-world clinical setting of primary care PBRNs with the academic medical center enrolling the rest. Multiple obstacles to standing up the study were encountered by the PBRNS. CONCLUSIONS: Primary care PBRNs rely largely on the goodwill established between academic health centers and participating practices. For future investigations involving device studies, collaborating PBRN leaders should assess whether recruitment criteria may change, obtain detailed lists of equipment needed, and/or know if the study is likely to be halted suddenly to appropriately prepare their member practices.

The Importance of Practice Facilitation in Primary Care When Pandemic Takes Hold: Relationships of Resilience.

The COVID-19 pandemic is unprecedented in recent history as radically and forcefully changing healthcare delivery. Practice facilitators, who often use tools of improvement science, have long played a critical role in supporting routine primary care practice transformation when healthcare system and policy changes occur. However, current events have taken many healthcare systems to the brink of collapse. Our practice facilitation team, which has a long history of sustained primary care partnerships in rural under-resourced settings, is finding creative solutions to carry forward work in research and quality improvement, and the tools of improvement science are well-suited to address rapidly changing demands of primary care during such a crisis. We reflect here on practice facilitation through the pandemic-the value of applied improvement science, and the critical necessity of strong relationships, flexibility, and creativity to support ongoing primary care partnerships.

A methodology for the customization of hinged ankle-foot orthoses based on in vivo helical axis calculation with 3D printed rigid shells.

This study aims to develop techniques for ankle joint kinematics analysis using motion capture based on stereophotogrammetry. The scope is to design marker attachments on the skin for a most reliable identification of the instantaneous helical axis, to be targeted for the fabrication of customized hinged ankle-foot orthoses. These attachments should limit the effects of the experimental artifacts, in particular the soft-tissue motion artifact, which affect largely the accuracy of any in vivo ankle kinematics analysis. Motion analyses were carried out on two healthy subjects wearing customized rigid shells that were designed through 3D scans of the subjects' lower limbs and fabricated by additive manufacturing. Starting from stereophotogrammetry data collected during walking and dorsi-plantarflexion motor tasks, the instantaneous and mean helical axes of ankle joint were calculated. The customized shells matched accurately the anatomy of the subjects and allowed for the definition of rigid marker clusters that improved the accuracy of in vivo kinematic analyses. The proposed methodology was able to differentiate between subjects and between the motor tasks analyzed. The observed position and dispersion of the axes were consistent with those reported in the literature. This methodology represents an effective tool for supporting the customization of hinged ankle-foot orthoses or other devices interacting with human joints functionality.

Human Papillomavirus Immunization in Rural Primary Care.

INTRODUCTION: Despite the safety and efficacy of the human papillomavirus vaccine, thousands are impacted by human papillomavirus and its related cancers. Rural regions have disproportionately low rates of human papillomavirus vaccination. Primary care clinics play an important role in delivering the human papillomavirus vaccine. A positive deviance approach is used to identify workflows, organizational factors, and communication strategies in rural clinics with higher human papillomavirus vaccine up-to-date rates. Positive deviance is a process by which exceptional behaviors and strategies are identified to understand factors that enable success. METHODS: Rural primary care clinics were rank ordered by human papillomavirus vaccine up-to-date rates using 2018 Oregon Immunization Program data, then recruited via purposive sampling of clinics in the top and bottom quartiles. Two study team members conducted previsit interviews, intake surveys, and 2-day observation visits with 12 clinics and prepared detailed field notes. Data were collected October-December 2018 and analyzed using a thematic approach January-April 2019. RESULTS: Four themes distinguished rural clinics with higher human papillomavirus vaccine up-to-date rates from those with lower rates. First, they implemented standardized workflows to identify patients due for the vaccine and had vaccine administration protocols. Second, they designated and supported a vaccine champion. Third, clinical staff in higher performing sites were comfortable providing immunizations regardless of visit type. Finally, they used clear, persuasive language to recommend or educate parents and patients about the vaccine's importance. CONCLUSIONS: Positive deviance identified characteristics associated with higher human papillomavirus vaccine up-to-date rates in rural primary care clinics. These findings provide guidance for rural clinics to inform human papillomavirus vaccination quality improvement interventions.

Public perception of predictive cancer genetic testing and research in Oregon.

The potential for using widespread genetic testing to inform health care has become a viable option, particularly for heritable cancers. Yet, little is known about how to effectively communicate the benefits and risks of both personal genetic testing and participation in biorepositories that aid scientific advancements. Nationwide efforts are engaging communities in large genetic studies to better estimate the population-wide prevalence of heritable cancers but have been met with hesitance or declination to participate in some communities. To successfully engage an Oregon population in longitudinal research that includes predictive genetic testing for pathogenic or likely pathogenic variants associated with an increased risk for cancer, researchers conducted 35 focus groups (two of which were held in Spanish) in 24 of Oregon's 36 counties to better understand knowledge and attitudes related to genetic testing and willingness to participate in longitudinal genetic research. A total of 203 adults (mean = 45.6 years; range 18-88), representing a range of education levels and prior knowledge of genetic research, participated in the focus groups. The majority (85%) of participants reported personal or family diagnoses of cancer (e.g., self, family, friends). A majority (87%) also reported a strong interest in cancer genetic testing and receiving genetic information about themselves. Nearly all focus groups (94%, 33 of 35 sites) included participant discussion citing their families (e.g., children, close relatives, and extended family members) as key motivators for participation in genetic research. For example, participants reported interest in increasing personal knowledge about their own and their families' cancer risks in order to respond proactively, if a pathogenic variant was found. While most focus groups (94%, 33 of 35 sites) included participant discussion describing barriers to predictive genetic, testing such as concerns about outcomes, the desire to learn about health risks in oneself mitigated or outweighed those fears for many participants. Other commonly reported concerns were related to potential mistrust of insurance companies, researchers, or institutions, or lack of knowledge about genetics, genetic testing, or genetic research. Participants, particularly in rural areas, highlighted critical factors for research recruitment, such as trust, personal interaction, public education about genetic research, and clear communication about study goals and processes. Our statewide findings reflect that public interest in predictive cancer genetic testing and cancer genetic research can surpass lack of knowledge of the complex topics, particularly when benefits for self and family are emphasized and when study considerations are well articulated.

A stepped-wedge cluster randomized trial designed to improve completion of HPV vaccine series and reduce missed opportunities to vaccinate in rural primary care practices.

OBJECTIVES: To test the effectiveness of a comprehensive team-based intervention to improve human papillomavirus (HPV) vaccination completion rates and reduce missed opportunities to vaccinate in rural Oregon. DESIGN: Stepped-wedge cluster randomized trial. PARTICIPANTS: Forty family physicians and pediatricians who are members of the Oregon Rural Practice-based Research Network. INTERVENTION: Tailored to individual practice needs, components will include (1) practice facilitation with clinicians, nurses, front office staff, and others who have patient contact to redesign patient care and communication strategies to optimize HPV vaccine series completion; (2) workflow mapping adapted to practice context to support HPV vaccine delivery; (3) a practice improvement model designed to firmly establish reminder and recall systems and then standing orders; (4) education for patients and parents that underscores HPV vaccination is safe, effective, and an important approach for reducing cancer risk; and (5) partnering with community organizations to plan and implement a social marketing campaign on HPV vaccination. MAIN OUTCOME MEASURES: Initiation and completion of the HPV vaccine series as well as reduction in rates of missed opportunities to vaccinate derived from Oregon Immunization Program data. TRIAL REGISTRATION: ClinicalTrials.govPRS, NCT03604393 : .Trial was registered on July 11, 2018. The first participant was enrolled on September 11, 2018.

κ Agonists as a novel therapy for menopausal hot flashes.

OBJECTIVE: The etiology of postmenopausal hot flashes is poorly understood, making it difficult to develop and target ideal therapies. A network of hypothalamic estrogen-sensitive neurons producing kisspeptin, neurokinin B and dynorphin-called KNDy neurons-are located adjacent to the thermoregulatory center. KNDy neurons regulate pulsatile secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). Dynorphin may inhibit this system by binding κ opioid receptors within the vicinity of KNDy neurons. We hypothesize that hot flashes are reduced by KNDy neuron manipulation. METHODS: A double-blind, cross-over, placebo-controlled pilot study evaluated the effects of a κ agonist. Hot flash frequency was the primary outcome. Twelve healthy postmenopausal women with moderate to severe hot flashes (aged 48-60 y) were randomized. Eight women with sufficient baseline hot flashes for statistical analysis completed all three interventions: placebo, standard-dose pentazocine/naloxone (50/0.5 mg), or low-dose pentazocine/naloxone (25/0.25 mg). In an inpatient research setting, each participant received the three interventions, in randomized order, on three separate days. On each day, an intravenous catheter was inserted for LH blood sampling, and skin conductance and Holter monitors were placed. Subjective hot flash frequency and severity were recorded. RESULTS: The mean (SEM) hot flash frequency 2 to 7 hours after therapy initiation was lower than that for placebo (standard-dose κ agonist, 4.75 [0.67] hot flashes per 5 h; low-dose κ agonist, 4.50 [0.57] hot flashes per 5 h; placebo, 5.94 [0.78] hot flashes per 5 h; P = 0.025). Hot flash intensity did not vary between interventions. LH pulsatility mirrored objective hot flashes in some--but not all--women. CONCLUSIONS: This pilot study suggests that κ agonists may affect menopausal vasomotor symptoms.

The characteristic ultrasound features of specific types of ovarian pathology (review).

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner's subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images.

Reliability and validity of two four-level emergency triage systems.

OBJECTIVE: To measure and compare the reliability and predictive validity of a four-level triage system (I-4L) and the new four-level model triage emergency method (TEM). METHODS: This observational study was conducted in an urban hospital. Ten nurses were randomly selected to assign a triage level to 189 paper scenarios, using either the I-4L model (5 nurses) or the TEM model (5 nurses). We used weighted kappa statistics to measure the interrater and intrarater reliability of each triage tool and assessed the validity of each models based on the accuracy in predicting admission. RESULTS: Interrater reliability was kappa=0.73 [95% CI (confidence interval): 0.59-0.87] and kappa=0.79 (95% CI: 0.65-0.93) with I-4L and TEM, respectively. Intrarater reliability was kappa=0.82 (95% CI: 0.67-0.96) and kappa=0.78 (95% CI: 0.62-0.93), respectively. The accuracy of triage rating for admission prediction was similarly good with I-4L and TEM, namely, 79% (95% CI: 74-85) and 77% (95% CI: 74-85). The proportion of patients admitted per triage level was similar with the two models. CONCLUSION: The interrater and intrarater reliability for rating triage acuity and for accuracy in patient admission prediction was good with both models. Performance with the new model was similar to that of I-4L despite the nurses' short experience. The new TEM model has the advantage of predicting utilization of emergency department resources.