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Because longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at 3 VETSA assessments beginning at average age 56. The same GCA index was used throughout. Higher young adult GCA and better GCA maintenance were associated with stronger specific cognitive abilities from age 51 to 73. Given equivalent GCA at age 56, individuals who had higher age 20 GCA outperformed those whose GCA remained stable in terms of memory, executive function, and working memory abilities from age 51 to 73. Thus, paradoxically, despite poorer maintenance of GCA, high young adult GCA still conferred benefits. Advanced predicted brain age and the combination of elevated vascular burden and APOE-ε4 status were associated with poorer maintenance of GCA. These findings highlight the importance of distinguishing between peak and current GCA for greater understanding of cognitive aging.

Background: Given the physical and mental health consequences of tobacco use amongst individuals with mental illness, it was imperative to assess the burden of tobacco use in this population. Aim: This study examined the patterns and factors associated with tobacco use in individuals attending the outpatient unit. Setting: Cecilia Makiwane Hospital Mental Health Department in Eastern Cape province, South Africa. Methods: Lifetime (ever use) use and current use of any tobacco products were examined in a cross-sectional study of 390 individuals between March and June 2020. A logistic regression was fitted to determine the correlates of lifetime and current use of any tobacco products. Results: The rates of ever use and current use of tobacco products were 59.4% and 44.6%, respectively. Of the participants interviewed, lifetime tobacco use was more prevalent amongst individuals with schizophrenia (67.9%) and cannabis-induced disorders (97.3%) and lower in those with major depressive disorders (36.1%) and bipolar and related disorders (43.5%). Men were six times more likely to have ever used or currently use tobacco products in comparison to women. Also, those who had a salaried job or owned a business were over three times more likely to have ever used or currently use tobacco products compared with those receiving government social grants. Conclusions: The prevalence of tobacco use in this study was significantly higher than the general population in the Eastern Cape. Therefore, smoking prevention and cessation interventions targeted at the general population should target this often neglected sub-population in the region.

PURPOSE Addressing financial toxicity among cancer patients is a complex process that requires a multifaceted approach, particularly for rural patients who may face additional cost-related barriers to care. In this study, we examined interventions being implemented by financial navigation staff at various cancer centers that help address financial toxicity experienced by oncology patients. METHODS We conducted semistructured interviews with a convenience sample of financial navigation staff across 29 cancer centers in both rural and urban areas in 7 states. Interviews were audio-recorded and transcribed. Descriptive coding and thematic analysis techniques were used to analyze the data. FINDINGS Thirty-five participants were interviewed, the majority of whom worked in cancer centers located in rural counties. Participants identified the use of screening tools, patient education, and access to tailored financial assistance resources as best practices. Immediate resource needs included additional financial navigation staff, including lay navigators and community health workers, to promote linkages to local resources. Suggested clinical areas for intervention included proactive and early implementation of financial assessments and discussions between providers and patients, along with training and access to regularly updated resources for those in financial navigator/counselor roles. Participants also discussed the need for policy-level interventions to reform health systems (including employment protections) and health insurance programs. CONCLUSIONS Implementing proactive methods to screen for and address financial needs of patients is essential to improving cancer-related outcomes. Additional programs and research are needed to help establish systematic and standardized methods to enhance financial navigation services, especially for underserved rural communities.

OBJECTIVES To examine associations between alcohol use and cognitive performance among older adults in Greece and the United States, and assess potential differences due to differing drinking practices in the two countries. METHODS Data came from Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) and National Alzheimer's Coordinating Center Uniform Dataset (NACC). We examined those aged 65-90 years at baseline who had no cognitive impairment and complete data for cognitive and alcohol use variables (N = 1110 from HELIAD; N = 2455 from NACC). We examined associations between current alcohol use and frequency of such use with cognitive performance on various cognitive tasks stratified by gender. RESULTS In NACC, use of alcohol was associated with better cognitive performance. Men drinkers performed better than non-drinkers on Trail A (standardized mean 0.07 vs. -0.24, p

Purpose: The primary purpose of this policy analysis is to examine how states changed their principal performance evaluation systems since the passage of Every Student Succeeds Act in 2015. In particular, we focus on whether states have capitalized on the flexible policy landscape to make space for meaningful family and community engagement (FCE) in assessing principals’ effectiveness. Research Methods: This study uses document analysis to review the structure of principal evaluation systems in all 50 states and selects 17 revised systems for a deeper review of their approach to leadership for partnering with families and communities. Findings: A plurality of states have not substantively revised their evaluation systems. Several of the revised systems narrowly focused on instructional leadership and student achievement measures and were thus unsupportive of meaningful FCE and federal policy aims for schools to work in partnership with family and community stakeholders. The principal evaluation systems most supportive of authentic family and community engagement allowed for flexible goal setting and explicitly encouraged the use of stakeholder feedback as evidence of principals’ effectiveness. Implications for Research and Policy: The authors discuss the implications of the results in terms of 1.) expanding definitions of educational leadership to include tenets of authentic FCE, 2.) creating coherent yet compendious systems for school improvement, and 3.) planning for and implementing a developmental approach to the evaluation of school leaders.

BACKGROUND Researchers have identified lengthy diagnosis delays in patients with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders (hEDS/HSD), but the reason for these delays is unclear. OBJECTIVE This review seeks to synthesize the existing qualitative research about hEDS/HSD to understand the reasons for diagnosis delay. DATA SOURCES We searched PubMed, Scopus, CINAHL, Google Scholar, and Dissertations and Theses databases for all qualitative studies about hEDS/HSD that mentioned the diagnosis process. A total of 283 studies were retrieved, from which we identified 13 studies to include in this synthesis. CONCLUSIONS The reviewers identified and organized diagnosis delay themes under four overarching categories: disease, patient, provider, and system. Disease factors included the nature of the symptoms and lack of a confirmatory test. Patient factors included psychological and emotional responses, seeing multiple providers, and receiving multiple diagnoses. Provider factors related to limited knowledge and attitudes. System factors included silo-based health care systems and bureaucratic barriers. IMPLICATIONS FOR PRACTICE Diagnosis delays result from complex, overlapping, and interacting factors. Nurse practitioners have a critical role in improving care and reducing diagnosis delays in patients with hEDS/HSD. Further research is needed to understand the causes and consequences of diagnosis delays in hEDS/HSD.

Background Rural Latino children and adults are less active than urban and non-Latino counterparts. We examined physical activity (PA) patterns of rural Latino children and their parents, and explored parental beliefs about and reported barriers of Latino family physical activity. Latino families in a rural area in eastern Washington state, with children in grades 3–5 were included. Methods We used mixed methods. Children (n = 27) and parents (n = 25) wore an accelerometer for 5 days; parents (n = 31) participated in a semi-structured interview and completed a demographic survey. Parent and child activity levels were compared using paired t-tests; interviews were analyzed with qualitative content analysis. Results Although 100% children and 46% parents met physical activity guidelines, parents and children spent most of the day in sedentary behaviors. Parent-reported PA barriers included their long work hours, lack of transportation, and their child’s screen-time. Conclusion Addressing barriers and reducing sedentary time could increase PA of rural Latino families.

Background Greater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality. Methods and Results Patients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m2 were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m2 (interquartile range 33-53 mL/min/1.73 m2), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%–20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%–1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%–3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49). Conclusions Variability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.

A 3.5-month-old boy presented with a changing medium-sized congenital melanocytic nevus on his leg. Due to atypical features on dermoscopy and reflectance confocal microscopy (RCM), an excision of the area of concern was performed. Histopathology showed many of the pathological features usually associated with a diagnosis of melanoma in situ in older patients, but due to the young age of the patient, absence of mitoses, and the degree of atypia, a diagnosis of a dysplastic compound nevus arising in a congenital compound (predominantly dermal) nevus was favored. In our case, RCM corresponded to histopathology helped target the area of concern and map the clinical and subclinical components to facilitate an optimal biopsy.

Background and aims Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid-life would have older than predicted brain age 16-28 years later. Design Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early mid-life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid-life) and 68 years (early old age). Early mid-life alcohol use was also evaluated. Setting Population-based United States sample. Participants/cases Participants were male twins of predominantly European ancestry who served in the United States military between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves. Measurements Self-reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the Brain-Age Regression Analysis and Computation Utility software (BARACUS) program to create PBAD scores (chronological age-predicted brain age) acquired at average ages 56 (n = 493; 2002-08), 62 (n = 408; 2009-14) and 68 (n = 499; 2016-19). Findings In structural equation modeling, age 40 pack years predicted more advanced age 56 PBAD [β = -0.144, P = 0.012, 95% confidence interval (CI) = -0.257, -0.032]. Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking × alcohol interaction, predicted more advanced PBAD at age 56 (β = -0.166, P = 0.001, 95% CI = -0.261, -0.070) with additional influences at age 62 (β = -0.115, P = 0.005, 95% CI = -0.195, -0.036). Age 40 alcohol did not predict age 68 PBAD. Within-twin-pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD. Conclusions Heavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.

Background Open streets events, where roads are temporarily closed to motorized vehicles, can provide safe spaces for physical activity (PA) and become sustainable community infrastructure. Since 2016, we have collaborated with a rural community to implement an open streets event, named ciclovía. In 2019, ciclovía was adopted as a community-wide program. This paper describes the process of building and progressing a ciclovía from a research intervention to a community-adopted program and participation of a rural community in ciclovía. Methods We used community-based participatory research to foster bidirectional learning on how to optimize the content and implementation of ciclovía to be feasible and acceptable for rural communities. The community-academic partnership focused on: 1) understanding the science of ciclovía; 2) learning the implementation process; 3) creating tools to facilitate planning, implementation, and evaluation of ciclovía; and 4) developing transition steps from a research intervention to a community-adopted program. Results The progression of the research intervention to community adoption spanned 2 years. First, the partnership met quarterly to discuss the science of ciclovía, its utility, and its adaptation for rural communities. Second, the partnership studied processes that facilitated ciclovía implementation. Third, the partnership created the ciclovía planning guide and tools for communities to establish their own ciclovía. The guide included forming a planning committee, setting meeting and communication plans, marketing and promotion, and selecting evaluation tools. Fourth, the transition steps from research intervention to community adoption included creating roles and responsibilities, implementing ciclovía using the planning guide, and convening listening sessions for improvement on implementation. Community attendance at ciclovía doubled from 189 individuals (126 children and 63 adults) when it was a research intervention to 394 individuals (277 children and 117 adults) when it was a community program. Conclusions The progression from a research intervention to a community-adopted program encompasses multiple steps that involve bidirectional learning and partnership with the community. Lessons learned from this study are integrated into a disseminatable ciclovía planning guide.

Study design This was a survey of the surgeon members of the Lumbar Spine Research Society (LSRS). Objective The purpose of this study was to assess trends in surgical practice and patient management involving elective and emergency surgery in the early months of the coronavirus pandemic. Summary of background data The novel coronavirus has radically disrupted medical care in the first half of 2020. Little data exists regarding the exact nature of its effect on spine care. Methods A 53-question survey was sent to the surgeon members of the LSRS. Respondents were contacted via email 3 times over a 2-week period in late April. Questions concentrated on surgical and clinical practice patterns before and after the pandemic. Other data included elective surgical schedules and volumes, as well as which emergency cases were being performed. Surgeons were asked about the status of coronavirus disease 2019 (COVID-19) virus testing. Circumstances for performing surgical intervention on patients with and without testing as well as patients testing positive were explored. Results A total of 43 completed surveys were returned of 174 sent to active surgeons in the LSRS (25%). Elective lumbar spine procedures decreased by 90% in the first 2 months of the pandemic, but emergency procedures did not change. Patients with "stable" lumbar disease had surgeries deferred indefinitely, even beyond 8 weeks if necessary. In-person outpatient visits became increasingly rare events, as telemedicine consultations accounted for 67% of all outpatient spine appointments. In total, 91% surgeons were under some type of confinement. Only 11% of surgeons tested for the coronavirus on all surgical patients. Conclusions Elective lumbar surgery was significantly decreased in the first few months of the coronavirus pandemic, and much of outpatient spine surgery was practiced via telemedicine. Despite these constraints, spine surgeons performed emergency surgery when indicated, even when the COVID-19 status of patients was unknown. Level of evidence Level IV.

This qualitative study explores how play informs the making process in a media arts environment. Drawing on Dewey’s ([1938]1998). Concepts of experience, purpose, and freedom, we explore how play a...

Background: Hispanic/Latino populations experience significant barriers to colorectal cancer (CRC) screening. ProCRCScreen is a multicomponent CRC screening program that can help primary care clinics improve CRC screening rates, but it needs adaptation to better meet the health care needs of Spanish-speaking Hispanic/Latino populations. Methods: We conducted four focus groups with 22 Spanish-speaking Latino patients and used inductive qualitative content analysis to identify potential program adaptations. Results: We identified lack of social support for CRC screening and confusion about completing stool-based testing as important barriers to CRC screening. Participants recommended increased specificity of the fecal immunochemical test (FIT) instructions to increase the likelihood of successful test completion, especially for first-time screening. They also endorsed patient navigation for support in completing CRC screening. Discussion: We adapted the informational materials and workflows for the ProCRCScreen program. Future research to test the adapted program is needed.

Many global retailers in mature markets employ mergers and acquisitions (M&As) as an essential strategic tool to expand into foreign markets. Given the substantial presence of financial constraints...

Introduction: Rheumatoid arthritis (RA) is an autoimmune rheumatic disease which often found in daily practice and requires certain considerations in recognizing clinical appearance also managing the disease as it often causes permanent joint damage, disability, even premature death. This recommendation is expected to become the latest reference for diagnosis and management of RA in Indonesia. Methods: The steering committee was formed by the Indonesian Rheumatology Association (IRA) to formulate key questions; conduct literature search, selection, and review; then formulate recommendation statements for diagnosis, therapy, and monitoring of RA. Furthermore, the steering committee determined the level of evidence and grades of the recommendations. After that, the level of agreement (LOA) was determined for each item by panelists including rheumatology consultants who have been appointed by IRA to represent Indonesia regions. Results: The steering committee established 30 recommendations including diagnosis, the role of laboratory and radiology tests, general treatment, the use of glucocorticoids, sDMARD, bDMARD, and tsDMARD. This recommendation also discusses guidelines on monotherapy, combination therapy, treatment strategies (treat-to-target), tapering, and continuous clinical remission. Treatment on co-morbidities and complications are also included in brief. Conclusion: IRA recommendations regarding the diagnosis and management of RA was made by considering various aspects such as the availability of drugs and supporting facilities, socioeconomic and cultural conditions in Indonesia, as well as the latest research that can be applied to Indonesian population.

Androgen deprivation therapy (ADT) is the standard of care for treatment of nonresectable prostate cancer. Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we performed a comparative proteomic analysis of three in vivo, androgen receptor (AR)-responsive orthograft models of matched hormone-naïve prostate cancer and CRPC. Differential proteomic analysis revealed that distinct molecular mechanisms, including amino acid (AA) and fatty acid metabolism, are involved in the response to ADT in the different models. Despite this heterogeneity, Schlafen family member 5 (SLFN5) was identified as an AR-regulated protein in CRPC. SLFN5 expression was high in CRPC tumors and correlated with poor patient outcome. In vivo, SLFN5 depletion strongly impaired tumor growth in castrated conditions. Mechanistically, SLFN5 interacted with ATF4 and regulated the expression of LAT1, an essential AA transporter. Consequently, SLFN5 depletion in CRPC cells decreased intracellular levels of essential AA and impaired mTORC1 signaling in a LAT1-dependent manner. These results confirm that these orthograft models recapitulate the high degree of heterogeneity observed in patients with CRPC and further highlight SLFN5 as a clinically relevant target for CRPC. Significance: This study identifies SLFN5 as a novel regulator of the LAT1 amino acid transporter and an essential contributor to mTORC1 activity in castration-resistant prostate cancer.

We hypothesize that for disaster risk mitigation, many households, despite being aware of their risk and possible mitigation actions, never seriously consider doing anything about them. In mitigation-focused decisions, since there is no equivalent to warning messages, the decision process is likely to evolve over an extended time. We explore what activates hurricane mitigation protective action decisions through three research questions: (1) to what extent are homeowners unengaged in protective action decision making? (2) What homeowner characteristics are associated with lack of engagement? And (3) to what extent do different life events trigger engagement in the decision-making process? We use the Precaution Adoption Process Model to conceptualize engagement as distinct from decision making; the broader protective action decision-making literature to explore drivers of engagement; and Life Course Theory to examine potential transitions from unengaged to engaged. We use survey data of homeowners in North Carolina to examine these questions empirically. Findings suggest that one-third of respondents had never engaged in protective action decisions, that life experiences differ in their occurrence frequency and effect on households’ mitigation decisions, and that some events, such as renovating, reroofing, or purchasing a home may offer critical moments that could be leveraged to encourage greater engagement in mitigation decision making.

Strabismus is a genetically heterogeneous disorder with complex molecular and neurophysiological causes. Evidence in the literature suggests a strong role for motor innervation in the etiology of strabismus, which connects central neural processes to the peripheral extraocular muscles. Current treatments of strabismus through surgery show that an inherent sensorimotor plasticity in the ocular motor system decreases the effectiveness of treatment, often driving eye alignment back toward its misaligned pre-surgical state by altering extraocular muscle tonus. There is recent interest in capitalizing on existing biological processes in extraocular muscles to overcome these compensatory mechanisms. Neurotrophins are trophic factors that regulate survival and development in neurons and muscle, including extraocular muscles. Local administration of neurotrophins to extraocular muscles partially reversed strabismus in an animal model of strabismus. The hypothesis is that sustained release of neurotrophins gives more time for the ocular motor system to adapt to a slow change in alignment in the desired direction. The effect of neurotrophins on extraocular muscles is complex, as different neurotrophic factors have diverse effects on extraocular muscle contraction profiles, patterns of innervation, and density of extraocular muscle precursor cells. Neurotrophic factors show promise as a therapeutic option for strabismus, which may help to improve treatment outcomes and offset devastating amblyopia and psychosocial effects of disease in strabismus patients.

The epidemiological necessity for distancing during the COVID-19 pandemic has resulted in postponement of non-emergent hospitalizations and increase use of telemedicine. The feasibility of virtual antiarrhythmic drug (AAD) loading specifically with digital QTc electrocardiographic monitoring (EM) in conjunction with telemedicine video visits is not well established. We tested the hypothesis that existing digital health technologies and virtual communication platforms could provide EM and support medically guided AAD loading for patients with symptomatic tachyarrhythmia in the ambulatory setting, while reducing physical contact between patient and healthcare system. A prospective pilot, case series approved by the institutional ethics committee, entailing three subjects with symptomatic arrhythmia during the COVID-19 pandemic who were enrolled for virtual AAD loading at home. Clinicians met with participants twice daily via video visits conducted after QTc analysis (Kardia 6L mobile sensor) and telemetry review (Mobile Cardiac Outpatient Telemetry of silent arrhythmias). Participants received direct instruction to either terminate the study or proceed with the next single dose of AAD. All participants completed contactless loading of 5 AAD doses, without untoward event. Scheduled video visits allowed dialogue and participant counseling where decision making was guided by remote review of EM. Participant adherence with transmissions and scheduled visits was 98.3%; a single electrocardiogram was delayed beyond the two-hours-post-dose schedule. This virtual approach reduced overall expenditures based on retrospective comparison with previous AAD load hospitalizations. We found that a ‘virtual hospitalization’ for AAD loading with remote electrocardiographic monitoring and twice daily virtual rounding is feasible using existing digital health technologies., Graphical Abstract Graphical Abstract

Midlife vascular disease increases risk for dementia and effects of vascular dysfunction on brain health differ between men and women. Elevated pulse pressure, a surrogate for arterial stiffness, contributes to cerebrovascular pathology and white matter damage that may advance cognitive aging; however, it remains unclear how associations between pulse pressure and neural integrity differ by sex and age. This study used restriction spectrum imaging to examine associations between pulse pressure and brain microstructure in community-dwelling women (N=88) and men (N=55), aged 56 to 97 (mean, 76.3) years. Restricted isotropic (presumed intracellular), hindered isotropic (presumed extracellular), neurite density, and free water diffusion were computed in white matter tracts and subcortical regions. After adjustment for age and sex, higher pulse pressure correlated with lower restricted isotropic diffusion in global white matter, with more pronounced associations in parahippocampal cingulum, as well as in thalamus and hippocampus. Subgroup analyses demonstrated stronger correlations between pulse pressure and restricted isotropic diffusion in association fibers for participants ≤75 years than for older participants, with stronger effects for women than men of this age group. Microstructure in parahippocampal cingulum and thalamus differed by pulse pressure level regardless of antihypertensive treatment. Increased pulse pressure may lead to widespread injury to white matter and subcortical structures, with greatest vulnerability for women in late middle to early older age. Restriction spectrum imaging could be useful for monitoring microstructural changes indicative of neuronal loss or shrinkage, demyelination, or inflammation that accompany age-related cerebrovascular dysfunction.

Background The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared. Objective To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools. Methods An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures. Results The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other. Conclusion Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

Summary Objective Systematically review and synthesize guidelines, systematic reviews, or randomized controlled trials (RCTs) published between April 1, 2019 and April 30, 2020 which evaluated or made recommendations for rehabilitation of persons with osteoarthritis. Design Five electronic databases (Medline, EMBASE, Cochrane CENTRAL, CINHAL, Web of Science) were searched with a comprehensive search strategy. Guidelines for rehabilitation of persons with osteoarthritis, and systematic reviews and RCTs evaluating osteoarthritis rehabilitation that included at least one patient-reported outcome measure and/or clinical test of function were included. Two authors independently screened records and assessed methodological quality using the AGREE-II (guidelines), AMSTAR-2 (systematic reviews) or PEDro scale (RCTs). Data were extracted to summarize included records and a narrative synthesis of findings related to core recommended osteoarthritis rehabilitation treatments performed. Results Of 2,479 potential records, 253 records were reviewed. Two guidelines, 18 systematic reviews and 38 RCTs were included. 84% (n = 49) of included records related to knee osteoarthritis, 13% (n = 8) to hip, 10% (n = 6) to hand, 3% (n = 2) to mixed, and 1% (n = 1) to foot osteoarthritis. Exercise-therapy, methods to deliver exercise-therapy remotely, and approaches to facilitate exercise-therapy behaviour change were the most commonly evaluated interventions (n = 27). 94% of systematic reviews and 63% of RCTs rated high-quality. Conclusions Osteoarthritis rehabilitation research continues to focus on knee osteoarthritis and exercise-based interventions. Emerging topics include rehabilitation of comorbid populations, exercise behaviour change and technology supports. A better understanding of rehabilitation of osteoarthritis in joints other than the knee, and methods to determine and promote ideal exercise-therapy prescription are needed.

Background We examined the associations between dual impairments in visual and hearing acuity and aging-related cognitive decline. Methods This was a longitudinal study of adults who had visual and hearing acuity and cognitive function assessed in 1992–1996 and were followed for up to 24 years (mean = 7.3 years), with up to five additional cognitive assessments. Visual impairment was defined as vision worse than 20/40, hearing impairment as pure-tone average thresholds >25 dB. Associations were tested using linear mixed-effects regressions. Results Of 1,383 participants, 293 had visual impairment, 990 had a hearing impairment and 251 had both deficits. In fully adjusted models, low visual acuity was associated with poorer Mini-Mental State Examination (MMSE; β = −0.29) and Trail-Making Test Part B (Trails B; β = 13.22) performance, and with faster declines in MMSE (β = −0.12) and Trails B (β = 1.84). The combination of low visual and low hearing acuity was associated with poorer MMSE (β = −0.44) and Trails B (β = 11.20) scores, and with faster declines in MMSE (β = −0.19), Trails B (β = 3.50), and Verbal Fluency Test (VFT; β = −0.14) performance. Associations were similar in men and women. Conclusion Impairments in both vision and hearing are associated with a more rapid decline in cognitive function with aging.

We examined the association between dietary potassium intake and all-cause and cause-specific mortality among community-dwelling older adults. Potassium intake was assessed with a food frequency questionnaire administered to 1,363 older adults (mean age 71.0 ± 10.6 years). Cox proportional hazard regressions estimated hazard ratios for sex-specific quintiles of calorie-adjusted potassium in relation to all-cause and cause-specific (cardiovascular disease, CVD, and stroke) mortality, adjusting for numerous covariates. There were 855 deaths (63% mortality) during the 20-year follow-up. Relative to the third quintile, potassium intake in the lowest quintile only was associated with increased risk of all-cause mortality (fully-adjusted hazard ratio 1.33; 95% CI 1.06, 1.67). Potassium intake was not significantly associated with CVD or stroke mortality. These results suggest that low potassium intake is associated with increased risk of mortality independent of overall health status. Ensuring adequate potassium in the diet may be an important strategy for reducing risk of earlier mortality among older adults.

Among the most common causes of U.S. adult hospitalizations, pneumonia accounted for nearly 50,000 deaths in the United States in 2017. This article provides nurses with a thorough update on pneumonia risk factors, signs and symptoms, and diagnostic criteria, as well as inpatient treatment recommendations and recommendations for discharge and prevention, including the nurse's role in patient and family teaching. The article also details key similarities and differences between the new 2019 guideline jointly developed by the American Thoracic Society and the Infectious Diseases Society of America on diagnosis and treatment of adults with community-acquired pneumonia and their earlier 2007 guideline. One crucial difference is the growing recognition that the etiology of pneumonia is changing, necessitating the abandonment of prior categorizations of pneumonia type when determining antibiotic coverage in favor of reliance on local epidemiology and validated risk factors for antimicrobial resistance.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Duodenal eosinophilia may play a role in functional dyspepsia (FD), but existing study results are conflicted. We investigated the association between duodenal eosinophils (count and degranulation) and FD symptoms, accounting for atopic conditions, medications, and seasonal variations. In a cross-sectional study conducted in the Michael E. DeBakey VA Medical Center in Houston, Texas, we analyzed duodenal histopathology of 436 patient samples from a prospective cohort with a validated symptom survey data and chart reviews. FD was defined using Rome II symptom criteria. Eosinophil count was number per 5 high-power fields (HPF), and eosinophil degranulation was eosinophilic granules in the stroma both determined by two independent investigators. The study cohort was predominantly male (87.4%) with a mean age of 59.3 (standard deviation (SD) ± 9.8). Mean and median eosinophil counts were 75.5 (± 47.8) and 63 (IQR: 43, 101) per five HPF, respectively. Duodenal eosinophilia (defined as ≥ 63 per 5 HPF) and eosinophil degranulation were present in 50.5% and 23.1% of patient samples, respectively. FD was observed in 178 patients (41.7%), but neither the mean eosinophil count nor duodenal eosinophilia was associated with FD. Eosinophil degranulation was independently associated with FD overall (OR 1.74; 95% CI 1.08, 2.78; p = 0.02) and early satiety (OR 2.04; 95% CI 1.26, 3.30; p = 0.004). In this large, ethnically diverse cohort of adult patients, we found no significant association between duodenal eosinophilia and FD. However, the presence of duodenal eosinophilic degranulation, an activated eosinophil marker, was significantly associated with FD, especially early satiety.

With respect to supporting student well-being and success, the current research developed a peer support scheme, built on the principles of Social Identity Theory (SIT). This was targeted towards f...

Aim. To analyse the prevalence of self-care practices in T2D patients in KSA. Methods. The study was conducted in King Fahad Medical City (KFMC) in Saudi Arabia, and 385 patients were selected as samples. Data were collected using the Summary of Diabetes Self-Care Activities-Arabic (SDSCA) and consisted of 14 items related to self-care activities of T2D patients related to management and control of disease and four other aspects related to education and advice from healthcare members regarding management of T2D. Results. The self-care attributes including adherence to medication commitment activities ( M = 6.13 , SD = 1.25 ) were the most practised of all the domains. Glucose monitoring ( M = 4.15 , SD = 2.42 ) and foot care ( M = 3.28 , SD = 1.69 ) were at an average level, and adherence to the diet plan and exercise was found to be at a poor level ( M = 2.57 , SD = 1.73 and M = 2.13 , SD = 2.00 ) respectively. About 179 patients (74.3%) were found to be advised to follow a low-fat eating plan, and only 89 patients (36.9%) had received information concerning fruits and vegetables in their diet. More than 90% patients were found to be advised to strictly carry out exercise and blood sugar monitoring. Conclusion. It was found that adherence to self-care activities including diet, exercise, and foot care was relatively poor while intake of medication was strictly followed. The education provided by healthcare providers related to self-management attributes was found to be significant and had positive effects on the overall health and well-being of T2D patients.

Although a substantial body of evidence documents the potential effectiveness of the community school strategy, we are still determining why community schools have shown uneven results. To address ...

To identify and categorize barriers, facilitators, and strategies to boost exercise therapy adherence in youth with musculoskeletal conditions to inform research and clinical practice.Scoping review.We searched MEDLINE, CINAHL, SPORTDiscus, Scopus, PEDro, and ProQuest from inception to October 1, 2019.Studies written in English, with original data featuring an adherence barrier, facilitator, or boosting strategy for exercise therapy in youth (age, 19 years or younger) with musculoskeletal conditions, were included.Arksey and O'Malley's framework and the PRISMA Extension for Scoping Reviews guided data synthesis. Study quality was assessed with the Mixed Methods Appraisal Tool. Descriptive consolidation included study and sample characteristics, exercise therapy details, and adherence measurement specifics. Inductive thematic analysis of adherence barriers, facilitators, and boosting strategies followed Braun and Clarke's 6-step guide.Of 5705 potentially relevant records, 41 studies, representing 2020 participants (64% girls; age range, 2-19 years) with 12 different musculoskeletal conditions and multiple exercise therapy interventions, were included. Despite poor reporting of adherence concepts, time constraints, physical environment (eg, location), and negative exercise experiences were commonly identified barriers. Social support and positive exercise experiences were frequently identified facilitators. Reinforcement, exercise program modification, and education were recurring boosting strategies, despite being infrequent barriers or facilitators.A diversity of barriers to and facilitators of exercise therapy for youth with musculoskeletal conditions were identified. Efforts to link adherence-boosting strategies to an individual's needs should be considered. Making exercise enjoyable, social, and convenient may be important to maximizing adherence in this population.

Summary Background In‐person assessments of physical activity (PA) and body weight can be burdensome for participants and cost prohibitive for researchers. This study examined self‐reported PA and weight accuracy and identified patterns of misreporting in a diverse sample. Methods King, Pierce and Yakima county residents, aged 21–59 years (n = 728), self‐reported their moderate‐to‐vigorous PA (MVPA) and weight, in kilograms. Self‐reports were compared with minutes of bout‐level MVPA, from 3 days of accelerometer data, and measured weights. Regression models examined characteristics associated with underreporting and overreporting of MVPA and weight, the potential bias introduced using each measure and the relation between perceived and measured PA and weight. Results MVPA underreporting was higher among males and college educated participants; however, there was no differential MVPA overreporting. Weight underreporting was higher among males, those age 40–49 years and persons with obesity. Weight overreporting was higher among Hispanic participants and those reporting stress, unhappiness and fair or poor health. The estimated PA–obesity relation was similar using measured and self‐reported PA but not self‐reported weight. Perceived PA and weight predicted measured values. Conclusion Self‐reported PA and weight may be useful should objective measurement be infeasible; however, though population‐specific adjustment for differential reporting should be considered.

The purpose of this investigation was to assess the acute changes in growth factors associated with cognitive health following two ecologically valid, intense resistance exercise sessions. Twenty-nine late-middle-aged adults performed one session of either (a) moderate-load resistance exercise or (b) high-load resistance exercise. Venous blood was collected prior to warm-up, immediately following exercise and 30 min following exercise. Serum was analyzed for brain-derived neurotrophic factor, insulin-like growth factor 1, and vascular endothelial growth factor. Session intensity was determined by blood lactate concentration and session rating of perceived exertion. Postexercise blood lactate was greater following moderate-load when compared with high-load resistance exercise. Subjective session intensity was rated higher by the session rating of perceived exertion following moderate-load when compared with high-load resistance exercise. No differences were observed in serum growth factor levels between groups. Ecologically valid and intense moderate-load or high-load exercise methods do not alter serum growth factor levels in late-middle-aged adults.

During a 6-mo period, two 5-6 mo old female chinchillas (Chinchilla lanigera) were examined at the University of Colorado Anschutz Medical Campus after the discovery of firm, nonmobile masses in the left ventral cervical and left axillary region. Other than these findings and mild weight loss, both chinchillas' physical exams were normal. Bloodwork revealed an inflammatory leukogram characterized by leukocytosis, toxic neutrophils, lymphopenia, and monocytosis with mild, nonregenerative anemia. At necropsy, both masses were identified as abscesses. Streptococcus equi, subspecies zooepidemicus (S. zooepidemicus) was isolated in pure culture. Histology of the lungs, liver, spleen, and kidneys showed a marked increase in the numbers of both polymorphonuclear leukocytes and lymphocytes. Both animals were deemed unsuitable for research and were euthanized under isoflurane anesthesia by an intracardiac injection of pentobarbital sodium solution. S. zooepidemicus is an opportunistic, commensal organism found in the upper respiratory tract of horses. This organism has been documented to cause disease in other species and is zoonotic. Infections in humans have been reported, resulting in glomerulonephritis, endocarditis, septic arthritis, osteomyelitis, meningitis, and death. To aid in diagnosis and prospective surveillance of this bacteria, oral and nasal swabs were collected from the remaining cohort of chinchillas, and a qPCR screening assay was implemented. Within 12 mo, 4 of 41 additional females tested positive by culture or qPCR, resulting in a disease prevalence of 14% (6 of 43). However, only 2 of the additional 4 S. zooepidemicus positive animals developed clinical signs. The potential for the spread of infection, zoonosis, and adverse effects on research demonstrate that surveillance for S. zooepidemicus should be considered in a biomedical research environment.

This study determined what principals need to successfully lead community schools and the extent principals are prepared to lead them. The authors of this qualitative study collected data from a br...

The ability of sustained treatment of a single extraocular muscle with glial cell line-derived neurotrophic factor (GDNF) to produce a strabismus in infant non-human primates was tested. Six infant non-human primates received a pellet containing GDNF, releasing 2 µg/day for 90 days, on one medial rectus muscle. Eye alignment was assessed up to 6 months. Five of the six animals showed a slow decrease in eye misalignment from the significant exotropia present at birth, ending with approximately 10° of exotropia. Controls became orthotropic. Misalignment averaged 8° three months after treatment ended. After sustained GDNF treatment, few changes were seen in mean myofiber cross-sectional areas compared to age-matched naïve controls. Neuromuscular junction number was unaltered in the medial rectus muscles, but were significantly reduced in the untreated lateral recti. Neuromuscular junctions on slow fibers became multiply innervated after this sustained GDNF treatment. Pitx2-positive cells significantly decreased in treated and contralateral medial rectus muscles. Our study suggests that balanced GDNF signaling plays a role in normal development and maintenance of orthotropia. Sustained GDNF treatment of one medial rectus muscle resulted in a measurable misalignment largely maintained 3 months after treatment ended. Structural changes suggest mechanisms for producing an imbalance in muscle function.

Rationale & Objective Pulmonary hypertension (PH) contributes to cardiovascular disease and mortality in patients with chronic kidney disease (CKD), but the pathophysiology is mostly unknown. This study sought to estimate the prevalence and consequences of PH subtypes in the setting of CKD. Study Design Observational retrospective cohort study. Setting & Participants We examined 12,618 patients with a right heart catheterization in the Duke Databank for Cardiovascular Disease from January 1, 2000, to December 31, 2014. Exposures Baseline kidney function stratified by CKD glomerular filtration rate category and PH subtype. Outcomes All-cause mortality. Analytical Approach Multivariable Cox proportional hazards analysis. Results In this cohort, 73.4% of patients with CKD had PH, compared with 56.9% of patients without CKD. Isolated postcapillary PH (39.0%) and combined pre- and postcapillary PH (38.3%) were the most common PH subtypes in CKD. Conversely, precapillary PH was the most common subtype in the non-CKD cohort (35.9%). The relationships between mean pulmonary artery pressure, pulmonary capillary wedge pressure, and right atrial pressure with mortality were similar in both the CKD and non-CKD cohorts. Compared with those without PH, precapillary PH conferred the highest mortality risk among patients without CKD (HR, 2.27; 95% CI, 2.00-2.57). By contrast, in those with CKD, combined pre- and postcapillary PH was associated with the highest risk for mortality in CKD in adjusted analyses (compared with no PH, HRs of 1.89 [95% CI, 1.57-2.28], 1.87 [95% CI, 1.52-2.31], 2.13 [95% CI, 1.52-2.97], and 1.63 [95% CI, 1.12-2.36] for glomerular filtration rate categories G3a, G3b, G4, and G5/G5D). Limitations The cohort referred for right heart catheterization may not be generalizable to the general population. Serum creatinine data in the 6 months preceding catheterization may not reflect true baseline CKD. Observational design precludes assumptions of causality. Conclusions In patients with CKD referred for right heart catheterization, PH is common and associated with poor survival. Combined pre- and postcapillary PH was common and portended the worst survival for patients with CKD

Schizophrenia is a complex disorder that is diagnosed mainly with clinical observation and evaluation. Recent studies suggest that many people with schizophrenia have abnormalities in the function of the N-methyl- d -aspartate receptor (NMDAR). The retina is part of the central nervous system and expresses the NMDAR, raising the possibility of the early detection of NMDAR-related schizophrenia by detecting differences in retinal function. As a first-step, we used two non-invasive outpatient tests of retinal function, the photopic negative response (PhNR) of the light-adapted flash-electroretinogram (PhNR-fERG) and the pattern ERG (PERG), to test individuals with schizophrenia and controls to determine if there were measurable differences between the two populations. The PhNR-fERG showed that males with schizophrenia had a significant increase in the variability of the overall response, which was not seen in the females with schizophrenia. Additionally at the brightest flash strength, there were significant increases in the PhNR amplitude in people with schizophrenia that were maximal in controls. Our results show measurable dysfunction of retinal ganglion cells (RGCs) in schizophrenia using the PhNR-fERG, with a good deal of variability in the retinal responses of people with schizophrenia. The PhNR-fERG holds promise as a method to identify individuals more at risk for developing schizophrenia, and may help understand heterogeneity in etiology and response to treatment.

Background Infection is a well‐recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter‐defibrillator (S‐ICD). Although the AHA/ACC/HRS guidelines include recommendations for S‐ICD use, currently there are no clinical trial data that address the diagnosis and management of S‐ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S‐ICD infections. Two face‐to‐face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S‐ICD infections. Results Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. Conclusion Achieving expert panel consensus by process mapping methodology in S‐ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

An increasing number of national, state, and local programs have offered grants or other monetary incentives to encourage homeowners to retrofit their homes to reduce damage from natural hazard events. Despite this fact, little is known about how these offerings influence a homeowner’s decision to carry out such structural retrofits. This paper studies the impact that different grant program designs in particular have on the decision to undertake different types of retrofits to mitigate against hurricane damage. Using data from a survey of homeowners in the eastern half of North Carolina, we implement a mixed logit model that allows for the combination of both revealed-preference and stated-preference data available from the survey. Our findings show that offering a grant results in households being, on average, 3 times as likely to retrofit as when a grant is not offered. In addition, both the percentage of retrofit cost and the maximum dollar amount covered by the grant have a substantial impact on the probability that households choose to retrofit. Living closer to the coastline also has a significant impact on the probability that households will choose to retrofit. Counter to some previous research, we find that households who have experienced two or more hurricanes are less likely to choose to retrofit their homes. From our research, we find that the percentage of retrofit cost covered by the grant and the total cost are both important factors when deciding on the best grant program configuration.

Safely returning underserved youth to school during the coronavirus disease 2019 (COVID-19) pandemic through diagnostic testing and health education is imperative to mitigate the ongoing negative impact of COVID-19 and reduce health inequalities in underserved communities. The Rapid Acceleration of Diagnostics-Underserved Populations program is a consortium of research projects across the United States funded by the National Institutes of Health to understand the factors associated with the disproportionate burden of the pandemic among underserved populations and to leverage mitigation strategies, including diagnostic testing, with a focus on reducing health disparities. In this article, we provide an overview and introduce the articles from 8 Rapid Acceleration of Diagnostics-Underserved Populations projects featured in the supplement “Navigating a Pandemic in the K–12 Setting: Keeping Our School Communities Safe” published in Pediatrics. These projects funded in the program’s first phase focus on COVID-19 diagnostic testing approaches for youth and employees at schools in underserved communities to support safe in-person learning. In the articles comprising the supplement, researchers present barriers and facilitators of the community engagement process necessary to establish school-academic partnerships. These efforts showcase school-based implementation testing strategies during the COVID-19 pandemic but are translatable to tackling other challenges related to reducing health disparities.

Evidence suggests that coronavirus disease 2019 (COVID-19) testing in schools can add a layer of protection to reduce the spread of Severe Acute Respiratory Syndrome Coronavirus 2 and facilitate a safer return to in-person learning. Despite this evidence, implementation of testing in school settings has been challenging initially because of a lack of funding and limited availability of testing, but, as the pandemic has progressed and more funding and resources have been devoted to testing, other implementation challenges have arisen. We describe key implementation barriers and strategies that have been operationalized across 5 projects working to help schools with predominantly underserved populations who have faced significant COVID-19–related health disparities. We leveraged a key framework from the implementation science field to identify the challenges and used a matching tool to align implementation strategies to these challenges. Our findings suggest that the biggest obstacles to COVID-19 testing were the perceived relative advantages versus burden of COVID-19 testing, limited engagement with the target beneficiaries (eg, families, students, staff), and innovation complexity. Common strategies to overcome these challenges included identifying and preparing testing champions, altering incentive and allowance structures, assessing for readiness, and identifying barriers and facilitators. We aim to augment existing implementation guidance for schools by describing common barriers and recommended solutions from the implementation science field. Our results indicate a clear need to provide implementation support to schools to facilitate COVID-19 testing as an added layered mitigation strategy.

Background Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle chemoresistant prostate cancer by enhancing the efficacy of docetaxel. Methods We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs (n = 857) from repurposing libraries, with cytotoxicity quantified using High Content Imaging Analysis. Results Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment, no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival. Conclusions Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants further clinical evaluation.

What courage is required for an emerging leader to run for office as an independent candidate in a contested election? What changes when that leader is a young woman, challenging the status quo in a male-dominated political field? And finally, how does courage intersect leadership, what is required, learned, and tested when running for office means risking one’s life? This is the story of an emerging leader, Linda K. Sibanyoni, a candidate for political office from Zimbabwe, who is leading change in her community and who is willing to exercise the courage required to do so in new, different, and unexpected ways. Her lived experience is underpinned by the intersection of gender, power, and politics. From this story of trial, courage, and risk comes discussion around the leadership practices required for change in uncertain and unstable systems.

Women overdue for cervical cancer screening often have other preventive care gaps. We examined whether mailing unsolicited human papillomavirus (HPV) self-sampling kits to increase cervical cancer screening impacted receipt of other preventive services women were due for: mammography, colorectal cancer (CRC) screening, influenza vaccination, depression screening, and diabetic HbA1c monitoring. From 2014 to 2016, 16,590 underscreened women were randomized to receive a mailed kit or usual care Pap reminders within Kaiser Permanente Washington. We used logistic regression to estimate odds ratios (ORs) of preventive services receipt within 12-months between the intervention vs. control arms, and within the intervention arm (comparing those returning a kit vs. attending Pap vs. nothing), adjusting models for demographic variables. There were no significant between-arm differences in uptake of any of the preventive services: intervention vs. control: mammography OR = 1.01 (95% confidence interval:0.88-1.17), CRC screening OR = 0.98 (0.86-1.13), influenza vaccination OR = 0.99 (0.92-1.06), depression screening OR = 1.07 (0.99-1.16), HbA1c OR = 0.84 (0.62-1.13). Within the intervention arm, preventive services uptake was higher in women who completed cervical cancer screening vs. did not, with stronger effects for women who attended Pap: Pap vs. nothing: mammography OR = 11.81 (8.11-17.19), CRC screening OR = 7.31 (5.57-9.58), influenza vaccination OR = 2.06 (1.82-2.32), depression screening OR = 1.79 (1.57-2.05), HbA1c OR = 3.35 (1.49-7.52); kit vs. nothing: mammography OR = 2.26 (1.56-3.26), CRC screening OR = 5.05 (3.57-7.14), influenza vaccination OR = 1.67 (1.41-1.98), depression screening OR = 1.09 (0.89-1.33), HbA1c OR = 1.23 (0.57-2.65). Mailing HPV self-sampling kits to underscreened women did not negatively impact uptake of other preventive services. However, overall preventive service uptake was the highest among women who attended in-clinic cervical cancer screening.

Background Eosinophil-rich mucus plugs are a recognised feature of asthma and are believed to contribute to airflow obstruction. However, little is known about the incidence of plugging in severe eosinophilic asthma (SEA) and the relationship of plugging to other characteristics of this phenotype. In addition, it is unknown whether patients with evidence of plugging have a differential response to the eosinophil depleting anti-IL-5R therapy benralizumab. Methods Pre-biologic CT scans of patients with SEA treated with benralizumab were assessed by two radiologists independently. Patients were given a mucus score out of 20 (per segment plugged; score of 1–3 classed as plugging-low, score 34 as plugging-high). Baseline characteristics and clinical outcome following 1 year of treatment was compared between patients with and without evidence of plugging. Results CT scans of 116 patients with SEA were reviewed. 69/116 (59.5%) exhibited mucus plugging of which 40/116 (34.5%) were classed as plugging-high. Median (IQR) number of segments plugged was 4 (2–10.5). Baseline characteristics were similar between the plugging and no-plugging groups, with a trend towards lower baseline FEV1 in the plugging group (p=0.06). Nasal polyposis was more frequent in the plugging-high group (45%) compared to plugging low (24%) and unplugged (21%) groups (ANOVA p=0.04). Response to benralizumab at 1 year was comparable between those with and without plugging: AER reduction 3.67+/- 4.1 vs 3.17+/-3.47; change in ACQ6 0.73+/-1.1 vs 0.77+/-1.38; change in FEV1% 6.72+/-17.35 vs 6.50+/-18.3 (all p=NS). The number of plugged segments at baseline did not correlate with improvement in FEV1. Discussion Mucus plugging is identified in 60% of patients with SEA and is more commonly seen at high levels in patients with co-morbid nasal polyposis. Individuals with SEA and mucus plugging have a similar clinical response to eosinophil targeted therapy with benralizumab compared to patients with SEA but absent plugging on CT imaging.