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Thirty to seventy percent of all venous thromboembolism (VTE) events are associated with hospitalization. The absolute and relative risks during and after hospitalization are poorly characterized.Quantify the absolute rate and relative risk of VTE during and up to 3 months after medical and surgical hospitalizations.We conducted an observational cohort study between 2010 and 2016 of patients cared for by the University of Vermont (UVM) Health Network's primary care population. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate VTE risk.Over 4.3 years of follow-up, 55 220 hospitalizations (156 per 1000 person-years) and 713 first venous thromboembolism events (2.0 per 1000 person-years) occurred. Among individuals not recently hospitalized, the rate of venous thromboembolism was 1.4 per 1000 person-years and 71.8 per 1000 person-years during hospitalization. During the first, second, and third months after discharge, the rates of venous thromboembolism were 35.1, 11.3, and 5.2 per 1000 person-years, respectively. Relative to those not recently hospitalized, the age- and sex-adjusted HRs of venous thromboembolism were 38.0 (95% CI 28.0, 51.5) during hospitalization, and 18.4 (95% CI 15.0, 22.6), 6.3 (95% CI 4.3, 9.0), and 3.0 (95% CI 1.7, 5.4) during the first, second, and third months after discharge, respectively. Stratified by medical versus surgical services the rates were similar.Hospitalization and up to 3 months after discharge were strongly associated with increased venous thromboembolism risk. These data quantify this risk for use in future studies.

Background: Type 2 diabetes mellitus (DM) is more common in Black than White adults in the US. The inflammatory cytokine interleukin-6 (IL-6) is implicated in DM pathogenesis and circulates at higher levels in Black people. Metabolic syndrome (MetS), a group of conditions related to insulin resistance, often precedes or coexists with DM. Little evidence is available on associations of IL-6 with these disorders in Black people. Methods: REGARDS enrolled 30,239 Black and White adults in 2003-07 and conducted a follow up visit 9.5 years later. Baseline IL-6 was measured in a sample of 4,400 participants (equal by race/sex groups) attending both visits. Modified Poisson regression estimated relative risk (RR) by level of baseline IL-6 for incident DM among those without prevalent DM; similar analyses were conducted for MetS. Inverse odds weighting estimated the percent mediation of the racial disparity in incident DM by IL-6. Results: Incident DM occurred in 460/3,399 (14%) at risk, and there were 384/1,957 (20%) cases of incident MetS. As shown in the Figure , DM and MetS incidence increased across baseline IL-6 quartiles overall, with a steeper rise and higher incidence among Black than White adults. Adjusting for confounders, the RR of DM for IL-6 in the 4 th vs 1 st quartile was 1.91 (95% CI 1.38-2.65). Higher IL-6 was also associated with MetS (RR 1.65 (95% CI 1.22-2.22)). In adjusted models there were no material differences in these associations by race. The RR of DM in Black compared with White people was 1.90 (95% CI 1.59-2.27); there was no association of race with MetS. IL-6 significantly mediated 13.4% of the racial disparity in DM adjusting for demographic factors. Conclusions: Higher IL-6 is a risk factor for incident DM and MetS in Black and White adults. The race disparity in DM was partly mediated by IL-6. Interventions to reduce IL-6 may lower risk of DM and MetS and lessen the racial disparity in DM. Figure: Diabetes and Metabolic Syndrome Incidence (bars) and Relative Risk (95% CI) by Baseline IL-6 Quartile

Introduction: A prothrombotic state is implicated in the vascular complications of type 2 diabetes (DM), and such complications disproportionately affect Black compared to White adults. However, it is not known if this is due to DM or whether coagulation factor levels are related to DM incidence. Higher coagulation factor IX (FIX) was related to increased risk of CHD and stroke among Black but not White participants in the REGARDS cohort. We hypothesized higher FIX antigen would be associated with incident DM risk, with stronger relationships in Black versus White adults. Methods: REGARDS enrolled 30,239 Black and White adults from across the contiguous US from 2003-2006 with a second in-home visit from 2013-2016. The Biomarkers as MEDiators of Racial Disparities in Risk Factors (BioMedioR) nested cohort study included 4,400 participants who completed both visits, balanced on race and sex. Modified Poisson regression models estimated the RR of incident DM per 1-SD increment log FIX. We tested for a FIX-by-race interaction a priori due to differential associations of FIX with CHD and stroke by race in REGARDS. Results: Among 3,381 participants without baseline DM (mean age 63 years, 44% Black race, 51% women), 456 (13.5%) developed incident DM over 9.5-years. Adjusting for age, sex, and race, there was a significant difference in the association of FIX with DM by race (p-interaction Conclusions: Higher FIX levels were associated with incident DM risk. Relationships between FIX and incident DM were stronger for White than Black adults. The FIX-DM association may be due to adverse clinical and behavioral risk factors.

OBJECTIVES To quantify the extent of patient-level agreement among 3 published measures of low-value imaging for acute low back pain (LBP). STUDY DESIGN In this retrospective cohort study using commercial insurance claims from MarketScan, we assessed 3 published measures of low-value imaging for agreement in identifying LBP diagnoses (denominator), red-flag diagnoses (denominator exclusions), and imaging procedures (numerator). METHODS Using a cohort of patients, aged 18 to 64 years, with a diagnosis of LBP in 2014, we assessed agreement surrounding both the overuse event (imaging procedures) and inclusion in the reference population (LBP definition and exclusion diagnoses) using percent agreement and Fleiss κ among 3 overuse measures. RESULTS In our cohort of 1,835,620 patients with acute LBP, the 3 measures agreed 100% on the presence of acute LBP and also had excellent agreement (99%; κ = 0.98) in identifying imaging for LBP. However, there was substantial disagreement on whom to exclude for red-flag diagnoses, leading to lower agreement (75%; κ = 0.61) on whom to include in the reference population of acute LBP without red flags, among whom imaging for LBP is considered of low value. CONCLUSIONS Our findings demonstrate the need for further consensus surrounding how to translate guideline recommendations to administrative measures that assess overuse of imaging for acute LBP, particularly with respect to defining which patients should be excluded from the measures. This finding is also important for other overuse measures that rely on exclusions.

INTRODUCTION Television (TV) viewing may be associated with increased venous thromboembolism (VTE) risk independent of VTE risk factors including physical activity. This association was assessed in a large biracial US cohort of Black and White adults. METHODS Between 2003 and 2007 The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study recruited 30,239 participants aged ≥45 years, who were surveyed for baseline TV viewing and followed for VTE events. TV viewing was categorized as

Participatory research with young people centres their knowledge and experiences to generate research outcomes which are meaningful to them. In recent years, there has been an increase in participatory research within education, yet there is still little methodological insight into this approach. In this project, which explored adolescents’ reading motivation and engagement, a young people’s advisory panel was convened to ensure the perspectives and experiences of young people were central to the research. The panel consisted of 6 young people (13 – 15-years-old) from 3 schools in Scotland. The panel worked with researchers at the Universities of XX and XX and a national literacy organisation across one academic year to plan and design the project, carry out data collection and interpret the findings. To achieve this, online group meetings, an online interview training workshop, online 1-1 interviews with the first author and in person peer-interviews were conducted. In this article, the methodological practice of working with a young people’s advisory panel to carry out a research project is evaluated using thematic analysis of panel members’ reflections and meeting content. A discussion of the benefits, limitations, and practicalities are provided for researchers interested in working closely and collaboratively with young people to conduct educational research.

Distal arthrogryposis (DA) is a collection of rare disorders characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Remarkably, Botox and a dietary fatty acid that modulates PIEZO2 activity markedly reduce DA5-like deficits. This reveals an unexpected role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development.

Books have the power to take us on great adventures, immerse us in fantasy worlds, change our points of view, scare us, and make us laugh or cry. The characters bring the stories to life and join us on the journeys through the pages of our favorite reads. But have you ever thought about what might be happening in our brains when we let Harry Potter or Bella Swan take us on a fictional adventure? Psychologists have come up with some ingenious techniques to measure how we connect with characters in books, and they are still discovering how fictional characters might help us better understand ourselves and others. By conjuring up vivid images of different characters and letting us connect or empathize with them, books help us explore our own identities and put ourselves in other people’s shoes. Our favorite characters really can take us on the most incredible journeys!

Little information exists on incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts, and whether risk factors differ by race, sex or region in the US.Observational cohort study.4,198 Black and 7,799 White participants age ≥45, recruited 2003-2007 across the continental US with baseline eGFR60 ml/min/1.73mAge, sex, race (Black/White), region (stroke belt/other), education, income, systolic blood pressure, body mass index (BMI), diabetes, coronary heart disease, hyperlipidemia, smoking, albuminuria.1) eGFR change 2) incident CKD, defined as eGFR60 ml/min/1.73mLinear regression and modified Poisson regression were used to determine the association of risk factors with eGFR change and incident CKD, and stratified by race, sex and region.Participants were 63±8 years old, 54% female, and 35% Black. After 9.4±1.0 years follow-up, 9% developed CKD. In an age-, sex- and race-adjusted model, Black race (β -0.13, p0.0001) was associated with higher risk of eGFR change, but this was attenuated in the fully-adjusted model (β 0.02, p=0.54). Stroke belt residence was independently associated with eGFR change (β -0.10, p=0.0007) and incident CKD (RR 1.14 95%CI 1.01,1.30). Albuminuria was more strongly associated with eGFR change (β -0.26 vs β -0.17, pExcluded Hispanics, unknown duration and/or severity of risk factors.Established CKD risk factors accounted for higher risk of incident CKD in Black vs. White individuals. Albuminuria was a stronger risk factor for eGFR decline and incident CKD in Black compared to White individuals. Living in the US stroke belt is a novel risk factor for CKD.

Background: High C-reactive protein (a nonspecific inflammatory biomarker) is a risk factor for incident hypertension. The role of specific inflammation pathways in hypertension’s origins are unresolved. E-selectin, ICAM-1, and VCAM are cell adhesion molecules expressed by endothelial cells that aid leukocyte adhesion during inflammation. Their association with incident hypertension is unclear. Objective: To determine risk of incident hypertension by level of E-selectin, ICAM-1, and VCAM. Methods: REGARDS enrolled 30,239 Black and White US adults aged ≥45 years from across the continental US in 2003-2006, with a second exam in 2013-2016. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study included 4,400 REGARDS participants who attended both exams. We excluded participants with hypertension or missing biomarkers of interest at baseline. Hypertension was defined using a 140/90 mm Hg threshold or self-reported use of blood pressure (BP) lowering medications. Modified Poisson regression estimated relative risk (RR) of incident hypertension by baseline E-Selectin, ICAM-1, and VCAM. Results: Among 1,923 normotensive participants (mean [SD] age 71 [8] years, 36% Black race, 51% women) with 9 years median follow up, 37% developed hypertension. Baseline E-selectin and ICAM-1 but not VCAM were higher among Black participants and obese participants. In multivariable adjusted models, higher E-selectin was associated with greater risk of incident hypertension among White but not Black adults (P interaction = 0.05) in all but the final model ( Table ). Higher ICAM-1 and VCAM were not associated with risk of hypertension in any model. Conclusion: In a prospective study of Black and White US adults, E-selectin was associated with incident hypertension among White adults except when adjusting for medical comorbidities, including baseline systolic BP. Modification of E-selectin through behavioral interventions or medical therapies might be tested to lower risk of hypertension development.

Background: Much of chronic kidney disease (CKD) is unexplained by traditional risk factors. Endothelial dysfunction is highly prevalent in CKD and may be a potential target for reducing CKD incidence or progression. We sought to determine the association of plasma biomarkers of endothelial dysfunction with incident CKD in a large prospective cohort. Methods: REGARDS is a prospective population-based cohort of 30,239 Black and White US adults aged ≥45. Baseline biomarkers of endothelial dysfunction (plasma factor VIII, E-selectin, intercellular cellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1)) were measured in individuals without CKD who attended a second visit a median of 9.4 years after baseline. Incident CKD was defined as eGFR 2 and a decline of 40%. We used sequential logistic regression models adjusted for confounders to assess associations and tested for interactions by each of age, sex, race, and diabetes. Results: After exclusions, we studied 3,300 participants (median age 62, 49% women, 46% Black, 50% hypertensive, 15% diabetic). 228 (6.9%) developed CKD by the second visit. Substantial interactions were observed for several markers, so stratified analyses were presented (Table). In minimally adjusted models, independent positive associations with CKD were seen with higher levels of each marker: factor VIII in White non-diabetics, E-selectin in women Conclusion: Several plasma markers of endothelial dysfunction were highly relevant to CKD incidence in important subgroups, which may reveal insights into reducing the burden of CKD.

Background: Hypertension is a modifiable stroke risk factor, but hypertension severity isn't completely captured by blood pressure (BP) alone. Prior studies have shown that among adults with similar systolic BP, those taking a greater number of antihypertensive medications have greater stroke risk. However, count of antihypertension medications does not consider relative dose across classes and incompletely characterizes hypertension medical therapy. The recently described Hypertension Daily Dose (HDD) metric quantifies total dose of BP-lowering medications across multiple classes. The association between HDD and BP with stroke risk is unknown. Objective: Determine stroke risk by HDD and BP levels. Methods: We included Black and White adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study without prevalent stroke at visit 2 (2013-2017; treated as baseline) with follow-up data and full BP assessment. We classified systolic BP using JNC7 groupings and HDD by no BP medications and tertiles among those on BP medications. Cox proportional hazards models estimated hazard ratios (HR) for incident stroke by HDD group and BP group. Results: Of 13,265 participants included (mean age 72 [SD 8.5], 36% Black race, 56% women), 344 incident stroke events occurred during a median follow-up of 5.5 years. The stroke rate was higher among Black than White participants (5.6 vs. 5.0/1000 person-years). Relative to no BP medications and normotension, those with systolic BP ≥140 mm Hg and HDD in tertiles ≥2 had a 2.3x to 3.7x greater risk of incident stroke ( Table ). Those with systolic BP Conclusion: Among Black and White US adults without prevalent stroke, higher HDD was associated with greater risk of incident stroke in those with systolic BP ≥140 mm Hg, possibly reflecting greater disease severity and treatment resistance. These findings support aggressive BP control with antihypertensive medications to lower stroke risk among adults with hypertension.

Background: Cardiovascular disease is a major risk for cognitive impairment. The opioid precursor peptide pro-enkephalin A (PENK-A) is a circulating hormone associated with several cardiovascular diseases and possibly vascular dementia. The objective of this study was to test the association of plasma PENK-A with incident cognitive impairment and describe potential differences by age, race, and sex. Methods: REGARDS is a prospective population-based cohort of 30,239 Black and White adults. Baseline plasma PENK-A was measured in 462 participants who developed cognitive impairment over a median 4.7 years and 556 who did not develop this. PENK-A’s association with incident cognitive impairment was assessed by logistic regression models adjusted for confounders. We tested for differences by age, sex, and race with interaction terms. Results: PENK-A concentration was comparable between cases and controls, but higher with White race, female sex, greater age, coronary artery disease, and chronic kidney disease. Categorical and linear models did not reveal an association with cognitive impairment. Spline plots showed a non-linear association with decreased odds at very high PENK-A values (adjusted OR for 95 th vs 50 th percentiles 0.66, 95% CI 0.46-0.95). This association was only apparent after final adjustment for kidney function. Interaction testing showed substantial interactions by each age and sex (all P < 0.06). In subgroup analyses, shapes of association differed but no independent trends were discernable (Figure). Conclusions: Circulating PENK-A was not particularly associated with cognitive impairment odds. High levels may be protective; this finding could be spurious. Differences by sex and age may exist, expanding upon prior findings in REGARDS of differing non-linear associations with stroke by sex and race. Further work is needed to characterize the importance of endogenous opioid pathways to cardiovascular health and differences by demographic factors.

Background: Primary school children engage in a wide range of reading activities, yet we lack insights into why children choose to read different text types. Furthermore, recent studies of reading motivation have been dominated by quantitative research; however, qualitative research is necessary to ensure that children's voices are represented when we study their motivations to read. Methods: Thirty-three children (aged 9–11) from a single school in Scotland participated in individual interviews that focused on understanding their breadth of reading activities and why they chose to read different text types. Interviews were transcribed in full, and a data-driven inductive thematic analysis approach was used to ensure that the full complexity of the data was realised. Results: Children's reading motivation varied considerably across the different text types. For example, children read books to feel happy, relaxed, excited or to become immersed in the story. They also read books to develop their reading skills, because they felt reading was important, or because it was a habit or familiar. On the other hand, children read newspapers to stay informed, comics as they were fun and easy to read, interactive games as they could direct the narrative and audio books when they were tired. Overall, children reported a wide and diverse range of reading motivations, these being closely linked to the different text types they read. Conclusions: This study provides new insights into why children choose to read different text types and provides a strong foundation for further qualitative research aimed at gaining a detailed and comprehensive account of children's motivation for reading.

The authors explored adolescents’ reasons for reading or not reading books. In individual interviews with 39 adolescents (ages 15 and 16) in the United Kingdom, they reported that reading books offered an opportunity to relax, learn, escape the real world, and become immersed; was exciting, developed their empathy skills, and provided a form of social capital. However, challenges to book reading included a lack of time; that it was too effortful; that it was not encouraged, was expensive, or was uncool, or that students had simply lost the habit or grown out of it. Implications for high school classrooms are discussed, and the researchers argue that time, space, and/or initiatives to read for pleasure are important. Collaborative work among researchers, teachers, and engaged/disengaged adolescent readers is essential to ensure that these initiatives are optimal and reach and resonate with their intended audience.

Reading interventions measuring motivational outcomes in adolescence vary in terms of their theoretical frameworks, methodological approaches and findings. However, a review of these is not currently available. Drawing on narrative review principles, this article synthesises academic and grey literature to outline the breadth and scope of interventions which have measured changes in adolescents’ reading motivation and reflects upon those interventions identified. Key characteristics from the existing literature include a strong focus on struggling readers and skills-based goals. Outcomes of reading interventions measuring motivational effects among adolescents are mixed, and often not explicitly grounded in theory. There is also a notable absence of research taking account of the opinions and experiences of adolescents. There is need for much deeper exploration of “what works” for motivating adolescents to read; this should be based in established theory and centre the experiences of adolescents themselves.

Background Care homes have been particularly badly affected by the events of 2020. We acquired short-term resource from two streams to improve system resilience during winter. Aims To assess the impact of enhanced specialist palliative care to care homes regarding responsiveness, professional support and education, referrals, advance care planning (ACP), hospital admissions and deaths in preferred place of death (PPD). Methods A free education programme was offered to all care homes in Preston, Chorley and South Ribble commencing in November 2020. This was complemented by input from a Clinical Nurse Specialist over a total of six months. Results Between 1 January and 31 May 2021, 56 patients were referred. 69% from the hospital palliative care team. 46% of patients had cancer. Four patients died before they were assessed. 68% of patients were seen within seven days of referral. 29 patients died during the project timescale and 93% of deaths were in a care home. The only hospital admission was precipitated by an acute event. We found evidence that documentation of ACP and escalation of treatment plans improved by our intervention. Potential hospital admissions were avoided in 14 cases due to ACPs. There were challenges for carers in attending education, with 172 attendees over 34 sessions. With regard to visiting during a time of societal restrictions, 28% of review appointments took place face-to-face. Conclusions Education was well-received but further work is required to improve accessibility and to assess longevity of benefit. We responded clinically in a more timely manner, as compared to ‘normal care’. We identified a theme of inadequate and inconsistent documentation of future care planning.

OBJECTIVES: Hypercoagulability may be a key mechanism for acute organ injury and death in patients with severe coronavirus disease 2019, but the relationship between elevated plasma levels of D-dimer, a biomarker of coagulation activation, and mortality has not been rigorously studied. We examined the independent association between D-dimer and death in critically ill patients with coronavirus disease 2019. DESIGN: Multicenter cohort study. SETTING: ICUs at 68 hospitals across the United States. PATIENTS: Critically ill adults with coronavirus disease 2019 admitted to ICUs between March 4, 2020, and May 25, 2020, with a measured D-dimer concentration on ICU day 1 or 2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was the highest normalized D-dimer level (assessed in four categories: < 2×, 2–3.9×, 4–7.9×, and ≥ 8× the upper limit of normal) on ICU day 1 or 2. The primary endpoint was 28-day mortality. Multivariable logistic regression was used to adjust for confounders. Among 3,418 patients (63.1% male; median age 62 yr [interquartile range, 52–71 yr]), 3,352 (93.6%) had a D-dimer concentration above the upper limit of normal. A total of 1,180 patients (34.5%) died within 28 days. Patients in the highest compared with lowest D-dimer category had a 3.11-fold higher odds of death (95% CI, 2.56–3.77) in univariate analyses, decreasing to a 1.81-fold increased odds of death (95% CI, 1.43–2.28) after multivariable adjustment for demographics, comorbidities, and illness severity. Further adjustment for therapeutic anticoagulation did not meaningfully attenuate this relationship (odds ratio, 1.73; 95% CI, 1.36–2.19). CONCLUSIONS: In a large multicenter cohort study of critically ill patients with coronavirus disease 2019, higher D-dimer levels were independently associated with a greater risk of death.

OBJECTIVES: The opioid neuropeptide pro-enkephalin A (PENK-A) may be a circulating marker of cardiovascular risk, with prior findings relevant to heart failure, kidney disease, and vascular dementia. Despite these findings, the association of PENK-A with ischemic stroke is unknown, so we examined this association in a prospective cohort study and analyzed differences by race and sex. MATERIALS AND METHODS: The REasons for Geographic and Racial Differences in Stroke study (REGARDS) is a prospective cohort study of 30,239 Black and White adults. Plasma PENK-A was measured in 473 participants that developed first-time ischemic stroke over 5.9 years and 899 randomly selected participants. Cox models adjusted for demographics and stroke risk factors were used to calculate hazard ratios (HRs) of stroke by baseline PENK-A. RESULTS: PENK-A was higher with increasing age, female sex, White race, lower body mass index, and antihypertensive medication use. Each SD higher increment of PENK-A was associated with an adjusted HR of 1.20 (95% CI 1.01–1.42) for stroke, with minimal confounding by stroke risk factors. Spline plots suggested a U-shaped relationship, particularly in White men, with an adjusted HR 3.88 (95% CI 1.94–7.77) for the 95(th) versus 50(th) percentile of PENK-A in White men. CONCLUSIONS: Higher baseline plasma PENK-A was independently associated with future stroke risk in REGARDS. This association was most apparent among White men. There was little confounding by established stroke risk factors, suggesting a possible causal role in stroke etiology. Further research is needed to understand the role of endogenous opioids in stroke pathogenesis.

Background: Over the last two decades, the reading habits of children and adolescents have evolved. Research shows some similarities in the reading experiences of children and adolescents, but there are also differences. For example, adolescents are more likely to read digitally and generally report poorer attitudes towards reading. With this in mind, we asked: how do young people define a reader?Purpose: This small scale, in-depth study sought to understand how children and adolescents describe ‘a reader’ and examine similarities and differences in their responses.Methods: In total, 33 children aged 9–11 and 30 adolescents aged 15–16 from one primary school to one secondary school in the UK were individually interviewed, to explore their perceptions and descriptions of a reader. Using a participatory approach, adult researchers interviewed student researchers, who then in turn interviewed their peers. Transcribed data were analysed qualitatively, using a data-driven, inductive thematic analysis approach.Results: Our analysis revealed some common themes in terms of children and adolescents’ perceptions of a reader. For example, readers were described as those who enjoy reading, read frequently, choose to read and, primarily, read print books. Readers were also described as those who are skilled at reading. However, subtle differences between children and adolescents were also found. For example, adolescents were more likely to say that readers choose a broader range of reading matter and did not need to read as frequently to be described a reader.Conclusions and implications: Our analysis offers insights into how children and adolescents defined a reader. Understanding more about how children and young people describe readers may help teachers who are working towards strengthening reading cultures in their primary or secondary school contexts. Broadening the conceptualisation of what it means to be a reader could arguably lead to a more inclusive use of the term and ultimately encourage more children and adolescents to self-identify as readers. Further, from a methodological point of view, we encourage researchers to consider a participatory research approach where appropriate, as this involvement in the research process can support primary and secondary school students in the development of their own research skills.

Introduction: Multiple regulatory agencies and professional societies recommend risk assessment of hospitalized medical patients for hospital-acquired (HA) venous thromboembolism (VTE) and provision of pharmacologic prophylaxis to those at risk. Extant risk assessment models (RAMs) include risk factors not knowable or difficult to assess at admission and often do not include risk factors reflecting illness acuity (such as laboratory studies and vital signs at admission). We developed a RAM for HA-VTE that reports absolute VTE risk, as opposed to arbitrary risk categories, using only objective risk factors measured within the first 24 hours of admission. Methods: The study setting was a combined academic and community 540-bed teaching hospital in northwest Vermont (The University of Vermont Medical Center). Using validated electronic health record (EHR) derived phenotypes (computable phenotypes), we captured all medical admissions between 2010-2019 and examined patient demographics, past medical history, and presenting vital and laboratory measures as potential risk factors for HA-VTE. As risk assessment should happen within 24 hours of admission, we only assessed risk factors knowable within this timeframe. Individuals with VTE at admission were excluded. Key outcome and risk factor definitions were validated using chart review. Bayesian logistic regression with a least absolute shrinkage and selection operator (LASSO) prior probability distribution was used to select risk factors for the model. Variables with a t-statistic ≥1.5 or ≤-1.5 were included in the final model. Full or prophylactic anticoagulation use was adjusted for in the final model. Model performance was assessed using bootstrap resampling to estimate area under the receiver operating characteristic (AUC) curve and calibration slope with 95% confidence interval (CI). Results: There were 62,468 medical admissions in the study period with 219 HA-VTE events. Chart review demonstrated the positive predictive value of our HA-VTE computable phenotype to be 84% and the negative predictive value 99%. Mean age was 65 years and 51% were male. Comorbid conditions were common in this hospitalized population, including active cancer (29%), congestive heart failure (25%), diabetes (27%), hypertension (59%), and prior myocardial infarction (13%). Seven risk factors met the criteria for inclusion in the final model: prior history of VTE (OR 2.7; 95% CI 1.8, 3.8), red cell distribution width ≥14.7% (OR 1.6; 95% CI 1.2, 2.2), creatinine ≥2.0 mg/dL or on dialysis (OR 2.0; 95% CI 1.4, 2.8), serum sodium Discussion: We developed and internally validated a RAM for HA-VTE during medical hospitalization which incorporates simple, objective risk factors knowable within the first 24 hours of admission. Unlike most prior RAMs, this model also incorporates risk factors reflecting illness severity such as laboratory results. The RAM has good fit and calibration and will be moved forward to external validation. Future applications include incorporating the RAM into hospital admission workflows and assessing VTE prophylaxis rates and the incidence of HA-VTE and HA-bleeding. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Bleeding risk is understudied in recently discharged medical patients and often less appreciated than venous thrombosis risk. Knowledge of both absolute and relative bleeding risk in people recently discharged from medical hospitalizations is needed to balance the risks of thrombosis and bleeding. We therefore quantified the relative and absolute risk of bleeding requiring hospitalization in patients recently discharged (up to 3 months) after a bleeding-free medical admission. Methods: We followed all primary care patients aged ≥18 at the University of Vermont Medical Center's primary care clinics from July 2010 to September 2019, capturing all hospitalizations and bleeding events that followed these hospitalizations for 3 months after discharge. Using International Classification of Disease (ICD) 9 and 10 discharge diagnoses, laboratory values, current procedure terminology (CPT) codes and flowsheet data for transfusion support, we developed and validated computable phenotypes to identify bleeding events. Validation was performed manually by abstracting 150 charts with bleeding events detected by the phenotype and 40 charts without a bleeding event. Present on admission (POA)-bleeding was defined if bleeding occurred Results: From 2010-2019, among 67,571 people with a mean age of 48 years (56.7% female) followed for a median of 6.2 years, there were a total of 14,266 medical hospitalizations and 1,784 hospitalized bleeding events (568 HA and 1216 POA). The bleeding computable phenotype had a positive predictive value of 79% and a negative predictive value of >99%. The rate of bleeding in people with no hospitalizations within the past 3 months was 2.88 per 1000 person-years. Over the 1 month after discharge, the rate was 153.8 per 1000 person-years decreasing to 61 per 1000 person-years in the second month after discharge and 29 per 1000 person-years in the third month after discharge. The age- and sex-adjusted HR for bleeding was 26.9 the first month after discharged and decreased respectively to 15.3 and 8 over successive 1-month intervals after discharge, relative to those with no hospitalization in the past 3 months (Table). Conclusion: In this northern Vermont population, the three months after a medical hospitalization was associated with dramatically increased risk of hospitalization for bleeding compared to people with no recent hospitalizations. Findings demonstrate how common bleeding is after hospitalization and emphasize on the need to develop methods to quantify bleeding risk. Figure 1 Figure 1. Disclosures Al-Samkari: Novartis: Consultancy; Moderna: Consultancy; Argenx: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding.

Introduction Electronic health records (EHRs), allow use of large clinical databases to inform the practice of medicine. The impact of EHRs on research has been modest due to the lack of validated computable phenotypes for risk factors and outcomes. We developed and validated a computable phenotype for hospital-acquired (HA) venous thrombosis (VTE) to aid future studies about of HA-VTE. Methods The study population consisted of all admissions to the medical services (general medicine, cardiology, intensive care unit, and hematology / oncology) between 2010-19 at the University of Vermont (UVM) Medical Center, a 540-bed tertiary acute care hospital. HA-VTE was defined as a deep vein thrombosis of a lower or upper extremity or pulmonary embolism. Data used to develop the computable phenotype include International Classification of Disease (ICD) 9 or 10 discharge codes with the present on admission (POA) flag and current procedure terminology (CPT) codes with dates/times (which include imaging studies). We divided VTE into three groups; upper extremity deep venous thrombosis, lower extremity deep venous thrombosis, and pulmonary embolism, and selected CPT codes which could have diagnosed each VTE group. Our final definition consisted of a VTE ICD code not POA with a VTE site-specific CPT code (but not on the day of admission). We validated the algorithm by randomly abstracting 110 charts in 6 groups; 1) no VTE ICD codes, 2) VTE ICD code POA, 3) VTE ICD code not POA and no CPT code, 4) VTE ICD code not POA and with a CPT code on day 1 of admission, 5) VTE ICD code not POA with a CPT code on day 1 of admission and another 1+ day of admission (this group was incidentally discovered during our initial chart abstraction and validation) and 6) VTE ICD code not POA and with a CPT code after day 1 of admission (our computable phenotype of HA-VTE). We used survey methodology to determine the sensitivity and specificity of our computable phenotype for HA-VTE. Results Figure 1 shows our methodology and the results from the computable phenotype including how many admissions were analyzed and the total number of HA-VTE identified. For validation we abstracted 110 hospitalizations from the 6 identified groups using a standardized form. The results of the validation by abstraction group are presented in the Table. Using survey methodology, we estimate the incidence of HA-VTE to be 4.9 per 1000 admissions. Among the 20 patients with no VTE ICD code, there were no VTE events. Among the hospitalizations with VTE ICD codes which did not meet our computable phenotype definition of HA-VTE, 5 of 91 individuals had a HA-VTE. One individual had an incorrect POA flag, another had a non-vascular ultrasound which diagnosed the HA-VTE, and 3 admissions with HA-VTE were excluded due to having an imaging study on day 1. Among the 19 patients abstracted for our computable phenotype for HA-VTE, 16 had a HA-VTE. Among the three failures of our HA-VTE computable phenotype, 1 individual had a HA-superficial venous thrombosis (miscoded), the second individual had multiple imaging studies due to a high clinical suspicion, and the third had a VTE on admission (erroneous POA flag). The sensitivity and specificity of our computable phenotype for HA-VTE was 84.2% (CI 78.7-88.9%) and 99.8% (CI 99.77-99.84%). Conclusions We developed a computable phenotype for HA-VTE with adequate specificity and excellent sensitivity. This phenotype will be used to assess risk factors for HA-VTE and with appropriate validation to estimate the rates of HA-VTE at other institutions. Disclosures No relevant conflicts of interest to declare.

Introduction: Bleeding is an uncommon event but it is causes significant increase in morbidity and mortality. Identifying bleeding events using electronic health record data (both resulting from hospitalization and causing hospitalization) would allow the development of risk assessment models (RAM) to identify those at most risk. Traditional prospective cohorts for rare events are time consuming and expensive. We suggest a more efficient method using the electronic health record (EHR) data by developing and validating an algorithm to detect bleeding in hospitalized patients, ie, a "computable phenotype". Methods: We captured all admissions to the University of Vermont (UVM) Medical Center between 2010-19, a tertiary care medical center in northwest Vermont. Using International Classification of Disease (ICD) 9 and 10 discharge diagnoses, "present on admission" flags, problem lists, laboratory values, vital signs, current procedure terminology (CPT) codes, medication administration, and flowsheet data for transfusion support, we developed computable phenotypes for bleeding. Classification was based on the gold standard International Society of Thrombosis and Haemostasis definitions for clinically relevant non-major bleeding (CRNMB) and major bleeding (MB) and validated by medical record review. To improve sensitivity and specificity, algorithms were developed by bleeding site (intracerebral, intraspinal, pericardial, retroperitoneal, orbital, intramuscular, gastrointestinal, genitourinary, gynecologic, pulmonary, nasal, post-procedure, or miscellaneous). We preliminary validated the computable phenotype by randomly abstracting 10 medical records from each bleeding site. Results: Among 62,468 admissions, our computable phenotype for bleeding identified 10,202 bleeding events associated with hospitalization; 4,650 were CRNMB and 5,552 were MB. On chart abstraction, 135 of 153 hospitalizations had either a MB or CRNMB (88%, Figure). For MB, 95 of 119 (80%) of the computed MB phenytope events were validated. Of the 24 of 119 (20%) not validated, 14% (16) were CRNMB and 7% (8) the bleeding was present on coding but was not detected by chart review. Only 29%(10/34) of the CRNMB were validated. The most common error in the CRNMB computable phenotype was misclassification of 14 MB as CRNMB (41% of CRNMB. For individual bleeding sites, (figure), the algorithms performed well for most sites including intracerebral hemorrhage, gastrointestinal, and intramuscular bleeding, but performed less well for unusual and rarer bleeding sites (i.e. nasal). Conclusion: We developed a computable phenotype for bleeding which can be applied to our EHR system. The computable phenotype was specific for MB, but underestimated the severity of potential CRNMB. Importantly, we correctly classified specific important bleeding sites such as intracerebral, gastrointestinal, and retroperitoneal. This computable phenotype forms the basis for further refinement, and provides a road map for future studies on epidemiology of hospital-acquired bleeding and hospitalization for bleeding. Figure: Major and Clinically relevant non-major bleeding as detected by Electronic Health Record compared to the chart validation Figure 1 Disclosures No relevant conflicts of interest to declare.

In 2012-13, the Design Research Institute (DRI) at the RMIT University in Melbourne hosted a Design Challenge on ageing. For the institute, which is based around trans-disciplinary design research, the challenge provides a unique opportunity to introduce a rigorous framework and focus to its activities. Katherine Wilkinson, the Senior Manager of the DRI and initiator of the annual Design Challenge, describes how students, designers and experts from industry, business and the community were brought together by the issue of ageing to generate innovative ideas and solutions.

The clock drawing (CD) task involves visual integration skills associated with parietal lobe function. Seven mild Alzheimer's Disease (AD) patients and 11 healthy elderly controls (EC) underwent functional magnetic resonance imaging (fMRI) scanning while viewing a radial motion (RM) task. This RM task in EC activated the bilateral secondary visual cortex and parietal regions, whereas AD patients activated only the right-sided secondary visual cortex. The magnitude of the fMRI signal in the left superior parietal lobe was positively correlated with performance on the CD task in AD patients. These findings suggest that complex visuospatial processing impairments reflect the underlying AD neuropathology in parietal regions.

Although functional brain imaging can lateralize language functioning and has the potential to assess the functional integrity of the mesial temporal lobe memory structures, imaging protocols are not currently available for clinical use. Assessing the risk of post-epilepsy surgery memory decline is an important part of treatment planning, and the Wada test remains the current technique. The Wada test is invasive and has limitations with respect to sensitivity and specificity. We describe an audit of 141 consecutive Wada test results looking at the base rate of failure and clinical characteristics of failure. The objective was to provide base rate data that support decision making regarding selective use of the Wada test. We conclude that right-handed patients with right temporal lesions who have strong verbal memory are very unlikely to fail and probably do not need to undergo the Wada test. Patients with left temporal lesions are more likely to fail regardless of handedness and regardless of baseline neuropsychological test data. We propose that until functional imaging protocols become available to supersede the Wada test, patients should be considered for the Wada test on a case-by-case basis.

Background “Effort tests” (i.e., tests that indicate whether appropriate effort is being made) are increasingly used in neuropsychological assessments. However, not all failures on effort tests are necessarily attributable to lack of effort. Understanding the factors that contribute to failure on effort tests has important clinical implications. Objectives This study aimed (a) to establish the extent to which patients with medically unexplained symptoms (MUS) presenting to neurology fail effort tests, (b) examine the performance of “mild” and “strong” simulators on effort tests, and (c) compare the performance of simulators and MUS patients. Methods Forty-three MUS patients, 35 mild simulators, and 39 strong simulators undertook a battery of effort tests. The groups were matched for age, estimated IQ, and gender. The MUS patients were not involved in litigation. Results The failure rate (defined as failing two or more effort tests) was 11% in the MUS group, 94% in the mild simulation groups, and 100% in the strong simulation group. Conclusions A minority of nonlitigant MUS patients who present to neurology fail effort tests. Possible reasons for this are discussed. In that they do not produce below-chance performance (in contrast with many of the simulators), there is no clear indication of deliberate failure, though this cannot be ruled out. The very high failure rate in the mild simulation group (who were instructed not to overact) indicates the sensitivity of effort tests to lack of effort and the value of including such tests in neuropsychological assessments.

Overactive bladder is a common condition that can be treated effectively in primary care by nurses. Supplementary nurse prescribing enables nurses with the appropriate qualification to provide holistic programmes of care for individuals with an overactive bladder. This article provides a summary of the current position of nurse prescribing in England and how it can be applied to this aspect of continence care.

Uses experiences in Bulgaria to exemplify market entry and control strategies employed by franchisors in a business environment that is geographically and culturally remote from the West. Carries out interviews in 1996 with Bulgarian franchisors and franchisees to test a number of hypotheses relating to issues including the type of franchisor, system densities, market entry strategies and monitoring tactics. Identifies 17 environmental factors ‐ cultural, organisational, political and legal ‐ which represent possible areas of conflict between the franchisor and franchisee. Establishes that franchisors adapt to a remote business environment in a variety of ways in respect of both market entry and monitoring strategies ; establishes some significant correlations between different types of franchisors and their strategies. Finds that western franchisors and Bulgarian owned firms often place different emphasis on the relative importance of environmental factors. Observes a broad variation in market entry tactics. Recommends that franchisors need to establish criteria to establish risks in remote business environments and devise appropriate strategies prior to entry.

This article provides a brief overview of the causes of urinary incontinence in older people and the factors that need to be taken into account when assessing and treating the condition.

Identifying and assessing patients in primary care helps to ensure effective treatment.

The prostate gland lies directly beneath the bladder in men. It is doughnut-shaped and fits around the urethra. The gland produces a milky fluid that contains nutrients (used by sperm) and several enzymes including phosphate specific antigen (PSA). Secretions from the gland enter the urethra via prostatic ducts and make up part of the volume of semen. They also contribute to sperm motility and viability. For unknown reasons, the prostate enlarges in the majority of men beyond middle age--a condition known as benign prostatic hyperplasia (BPH). Urinary symptoms often accompany the enlargement of the prostate.

Aim To investigate the perceptions and experience of Pakistani women who have urinary incontinence problems. Method Data were collected from a sample group of six Pakistani women with incontinence problems. A female Miripuri Punjabi speaker conducted and recorded semi-structured interviews with the women. The interviewer interpreted these recordings onto another tape. Data were then analysed and categorised. Results The women had low self-esteem and also felt sinful because of their incontinence. Muslim women are obliged to perform ritual cleansing and prayer five times a day. If they pass urine or faeces, or experience incontinence, they become unclean and prayer is denied until the act of ritual cleansing is repeated. The women used prayer to relieve stress caused by incontinence, but being unclean denied them this comfort, thus increasing stress. Some participants had become secretive and isolated. The women had developed three strategies to help them live with incontinence: risk reduction to reduce the number of incidents; management, which focused on coping with incontinent episodes; and problem-sharing with other women. Their inhibitions and language limitations prevented them from disclosing their problems clearly to health professionals and fully understanding advice they received. These inhibitions were reduced when they were treated by a female health professional. Having an interpreter present also increased satisfaction with treatment. Conclusion To provide an effective continence service to Pakistani women with incontinence, it is necessary for healthcare professionals to understand their cultural and religious identities.