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Asthma morbidity disproportionately impacts children from low-income and racial/ethnic minority communities. School-supervised asthma therapy improves asthma outcomes for up to 15 months for underrepresented minority children, but little is known about whether these benefits are sustained over time. We examined the frequency of emergency department (ED) visits and hospital admissions for 83 children enrolled in Asthma Link, a school nurse-supervised asthma therapy program serving predominantly underrepresented minority children. We compared outcomes between the year preceding enrollment and years one-four post-enrollment. Compared with the year prior to enrollment, asthma-related ED visits decreased by 67.9% at one year, 59.5% at two years, 70.2% at three years, and 50% at four years post-enrollment (all p-values< 0.005). There were also significant declines in mean numbers of total ED visits, asthma-related hospital admissions, and total hospital admissions. Our results indicate that school nurse-supervised asthma therapy could potentially mitigate racial/ethnic and socioeconomic inequities in childhood asthma.

This study summarizes employment benefits from across 155 U.S. allopathic medical schools, investigates differences in employment benefits according to institutional characteristics, and explores possible connections between employment benefits and institutional wealth. Employment benefits data were extracted from institutions' websites across four categories: time-off, time-away, retirement contributions, and Employee Assistance Programs (EAPs)/family benefits. This dataset was mixed with other publicly available datasets sourced through the Association of American Medical Colleges (AAMC), the American Council on Education (ACE), and the American Association of University Professors (AAUP) to conduct additional analyses. Nationally, medical schools offered an average of 31 vacation/sick days and 12 paid holidays. Schools typically offered 4 out of 8 time-away benefits. Employers' retirement contributions ranged from 3.0% to 15.5%, with a mean contribution of 8.5%. A total of 43.2% (67 of 155) of medical schools offered a pension. Collectively, private medical schools offered fewer time-away benefits and more EAP/family benefits compared to public schools. Universities with larger endowments per student were associated with a higher number of EAP/family benefits offerings (r = 0.543, p < 0.001). Institutional wealth did not influence other benefits offerings. The quantity/quality of most employment benefits offered at allopathic medical schools were wide-ranging, tended not to vary by region or school control, and were not a function of institutional wealth.

Coaching is a key lever for supporting professional learning in early childhood, and coaches serve a critical role in the coaching process. However, little is known about coaches themselves which is a critical gap in evaluating the efficacy of coaching and for making decisions around coaching policies and practices. This mapping review synthesizes the early childhood coaching research to identify the background characteristics and training experiences of early childhood (0--8) coaches. We reviewed 374 studies for information about coaches and their experiences in early childhood coaching. "Research Findings:" Coaches were experienced and educated; however, qualification requirements varied across studies. Coaches were generally part of the research team that conducted the study. Over 15 different terms were used to describe coaching. Only 145 studies provided information about coach training, which tended to be via workshops and focused on implementing a specific coaching model. Overall, we noted inconsistency in reporting and the absence of information across studies. "Practice and Policy:" These findings are a call to action for researchers. More consistency and thoroughness is needed in reporting of coach-level characteristics as well as the coach training process. Additionally, there is a need for a consensus on the definition of key coaching terms.

Background: Mast cells (MCs) have recently been implicated in lymphocytic scarring alopecias, which may share a common pathogenesis. MCs in central centrifugal cicatricial alopecia (CCCA) have not been studied. Objective: We looked for the presence of MCs in CCCA using 2 different stains to see if their numbers correlated with the number of hair follicles, the degree of inflammation and perifollicular fibrosis, disease duration and severity, and patient symptoms. Methods: We performed a retrospective review of biopsies of patients diagnosed with CCCA, tabulated MC counts and correlated them with histopathologic and clinical findings. Results: MC counts were significantly greater using immunoperoxidase staining with CD117 than Giemsa stain, and more were present when the isthmus level was included with the infundibulum. MC counts with CD117 immunostain significantly correlated with the degree of inflammation. MC counts with both stains were significantly associated with the degree of fibrosis independently and after controlling for other factors. Limitations: The study was limited by insufficient tissue remaining in a small number of the transversely cut blocks. Conclusion: Our findings may have therapeutic implications for CCCA and other types of lymphocytic scarring alopecia.

Abstract Achilles tendinopathy is a disabling condition that affects more than 50% of runners. Pre-clinical studies in a large animal model of naturally-occurring tendinopathy similar to human Achilles tendinopathy has shown benefits of autologous bone marrow-derived mesenchymal stem cell (MSC) implantation. However, MSCs are advanced therapies medicinal products (ATMPs), with strict regulatory requirements. Guided by the regulator we carried out a first in man study to assess the safety and efficacy of autologous MSC injection in human patients with non-insertional Achilles tendinopathy. Ten patients, mean age 47 with mid-portion Achilles tendon pain and swelling for more than 6 months, underwent autologous cultured cell injections (median 12.2 × 106, range 5–19 × 106 cells) into their Achilles tendon. At 24 weeks follow-up, no serious adverse reactions or important medical events were observed. MOXFQ, EQ-5D-5L, and VISA-A scores improved clinically at 12 and 24 weeks. VAS pain improved increasingly at 6, 12 and 24 weeks. MOXFQ Pain and VISA-A Scores improved > 12 points from baseline to 24 weeks in 8 patients. Maximum anteroposterior tendon thickness as measured by greyscale US decreased by mean 0.8 mm at 24 weeks. This phase IIa study demonstrated the safety of autologous MSC injection for non-insertional Achilles tendinopathy and provides proof-of-concept of the technique in patients, all of whom had previously failed conservative treatments for chronic disease and leads the way for a larger randomised controlled trial.

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen. Methods: Experiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, stimulated Raman scattering (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy. Main findings: 1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to low density lipoprotein (LDL) density; 3) Both in vitro and in vivo, when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress. Conclusion: The results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be an important factor in the partitioning of TG between cytosolic LDs and VLDL particles.

Esophageal dysmotility is identified as a contraindication to lung transplantation at some centers due to increased risks of acute rejection, pulmonary infection, and chronic lung allograft dysfunction. Phosphodiesterase-type 5 inhibitors (PDE5i) are a cornerstone pharmacotherapy for pulmonary arterial hypertension (PAH) and are known to exert off-target effects that may impact lung transplant candidacy, including impaired esophageal contractility and decreased lower esophageal sphincter tone. We report 2 patients with PAH who were initially declined listing for lung transplantation due to iatrogenic esophageal dysmotility induced by PDE5is. Upon discontinuation of PDE5i therapy, these patients experienced significant improvement in esophageal motility within 14 days and met the criteria for transplant listing at their centers. Recognizing and mitigating the off-target effects of PDE5i medications is critical for maximizing access to transplant for patients with PAH.

Summary: Background: Approximately 20% of adults in Vietnam have hypertension, and management of this chronic condition remains challenging. This study aimed to assess the effectiveness of a multicomponent intervention in reducing blood pressure (BP) in adults with uncontrolled hypertension. Methods: This cluster randomised controlled trial was conducted in sixteen communities (8 intervention and 8 comparison) in a rural setting in Vietnam (2017–2022). Consenting adults (aged ≥ 18 years) with uncontrolled hypertension were enrolled. Sixteen communities were equally randomised to an intervention or comparison group stratified by district. Consenting adults were assigned to study groups by community. The comparison arm received training sessions about hypertension prevention and management for health workers, and patient education materials. The intervention arm received training sessions about hypertension prevention and management for health workers, and patient education materials and three enhancement components including a storytelling intervention, home BP self-monitoring, and expanded community health worker services. The primary outcome was the difference in changes in patient's levels of systolic BP between the study groups over a 12-month follow-up period. Patients and outcome assessors were masked. Findings: A total of 671 patients (340: intervention, 331: comparison) were enrolled in the trial. The mean age was 66 years and 45% were men. At the 12-month follow-up, the mean systolic BP declined by 18.4 mmHg in the intervention group and 3.7 mmHg in the comparison group (differential decline of 14.7 mmHg [95% CI: 11.8–17.6]). The intervention group also achieved better BP control and medication adherence than the comparison group. There were no serious adverse events related to study participation. Interpretation: The results of this trial demonstrate that a multicomponent intervention can effectively reduce elevated BP in individuals with uncontrolled hypertension in Vietnam. Trial registration: This trial was registered at ClinicalTrials.gov, NCT03590691. Funding: National Heart, Lung, and Blood Institute.

Background: Infants with hypoplastic left heart syndrome (HLHS) or a variant are at risk of ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) prior to superior cavopulmonary connection (SCPC). Although the impact of these complications in isolation has been described, their effect in combination on attrition is poorly defined. Methods: A retrospective observational study of patients with HLHS or variants undergoing a Norwood procedure between 2008 and 2020 at a single center was performed. VD and AVVR were defined as moderate or severe when seen on 2 sequential echocardiograms outside the perioperative period. Attrition was defined as death, listing for heart transplant, or unsuitability for SCPC or transplant. Descriptive statistics and regression models were used for analysis. Results: A total of 397 patients were included, of whom 75% had HLHS and 57% had received a Blalock-Thomas-Taussig shunt. Isolated VD occurred in 9% of patients, AVVR occurred in 13%, and both occurred in 6%. Attrition prior to SCPC occurred in 19% of the overall cohort, in 52% of patients with combined VD and AVVR (odds ratio [OR], 5.2; 95% confidence interval [CI], 2.3-12.0; P

Acute cellular rejection (ACR) is one of the main risk factors for chronic allograft dysfunction, the primary contributor to poor long-term survival in lung transplant recipients. We sought to develop a blood-based transcriptomic risk score (TRS) to detect ACR in lung transplant recipients. We tested for the association of the TRS with ACR in a logistic mixed model. We analyzed 101 samples from 75 individuals. We identified 4 genes after application of the least absolute shrinkage and selection operator. The TRS was significantly associated with ACR (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.86-7.14, p

Introduction Brain cancer is the leading cause of cancer-related deaths in children and the majority of childhood brain tumors are diagnosed without determination of their underlying etiology. Little is known about risk factors for childhood brain tumors in Vietnam. The objective of this case-control study was to identify maternal and perinatal factors associated with brain tumors occurring in young Vietnamese children and adolescents. Methods We conducted a hospital-based case-control study at Viet Duc University Hospital in Hanoi, Vietnam. Cases consisted of children with brain tumors aged 0-14 years old admitted to the hospital from January 2020 to July 2022 while the controls were age and sex-matched hospitalized children diagnosed with head trauma. Perinatal characteristics were abstracted from hospital medical records and maternal medical, behavioral, and sociodemographic factors were collected through in-person interviews. Conditional logistic regression models were used to examine maternal and perinatal factors associated with childhood brain tumors. Results The study sample included 220 children (110 cases and 110 controls) whose average age was 8.9 years and 41.8% were girls. Children born to mothers aged greater than 30 years at the time of the child’s birth had a higher risk of childhood brain tumors compared to those born to mothers aged from 18 to 30 years old (OR = 2.55; 95% CI: 1.13-5.75). Additionally low maternal body mass index prior to the current pregnancy of

Abstract Background Heart failure and chronic obstructive pulmonary disease (COPD) are leading cause of death throughout the world. Few recent studies have, however, examined possible sex and type of heart failure (HFpEF, HFrEF, and unspecified/other heart failure) differences in the prevalence of these chronic conditions among nursing home residents. Objectives The aim of this study is to examine the magnitude of concomitant COPD and differences according to sex and heart failure type, in terms of the prevalence of COPD among nursing home residents with heart failure. Methods The principal study outcomes were examined in a cross‐sectional study of 97 495 US nursing home residents with heart failure using the 2018 Minimum Data Set. The diagnoses of heart failure and COPD were operationalized through a review of nursing home admission, progress notes, and physical examination findings. Results The average age of this study population was 81.3 ± 11.0 years, 67.3% were women, and 53.8% had COPD. A slightly higher prevalence of COPD was found among men than women. A higher proportion of unspecified heart failure type was found in both men and women, than reduced and preserved ejection fractions, respectively. In both men and women, there was a higher prevalence of COPD among those with various chronic conditions and current tobacco users. Conclusions COPD is highly prevalent among medically complex middle‐aged and older nursing home residents with heart failure. Future research should focus on increasing our understanding of factors that influence the risk and optimal management of COPD and heart failure to improve the quality of life for nursing home residents.

Abstract Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80–100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduces muscle FA uptake, raises circulating FAs, which remain in blood vessels, and lowers glucose, mimicking prominent Cd36 −/− mice phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.

Abstract Objective HbA1c is an insensitive marker for assessing real‐time dysglycemia in obesity. This study investigated whether 1‐h plasma glucose level (1‐h PG) ≥155 mg/dL (8.6 mmol/L) during an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) measurement of glucose variability (GV) better reflected dysglycemia than HbA1c after weight loss from metabolic and bariatric surgery. Methods This was a prospective cohort study of 10 participants with type 2 diabetes compared with 11 participants with non‐diabetes undergoing sleeve gastrectomy (SG). At each research visit; before SG, and 6 weeks and 6 months post‐SG, body weight, fasting lipid levels, and PG and insulin concentrations during an OGTT were analyzed. Mean amplitude of glycemic excursions (MAGE), a CGM‐derived GV index, was analyzed. Results The 1‐h PG correlated with insulin resistance markers, triglyceride/HDL ratio and triglyceride glucose index in both groups before surgery. At 6 months, SG caused 22% weight loss in both groups. Despite a reduction in HbA1c by 3.0 ± 1.3% in the diabetes group (p

Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3−/−) whereupon we observed ∼50% reduction of apolipoprotein B100 (ApoB100) secretion, accompanied by an increase in ApoB100 early presecretory degradation via a predominantly lysosomal mechanism. Despite defective particle secretion in ANGPTL3−/− cells, targeted lipidomic analysis did not reveal neutral lipid accumulation in ANGPTL3−/− cells; rather ANGPTL3−/− cells demonstrated decreased secretion of newly synthesized triglycerides and increased fatty acid oxidation. Furthermore, RNA sequencing demonstrated significantly altered expression of key lipid metabolism genes, including targets of peroxisome proliferator-activated receptor α, consistent with decreased lipid anabolism and increased lipid catabolism. In contrast, CRISPR/Cas9 LDL receptor (LDLR) deletion in ANGPTL3−/− cells did not result in a secretion defect at baseline, but proteasomal inhibition strongly induced compensatory late presecretory degradation of ApoB100 and impaired its secretion. Additionally, these ANGPTL3−/−;LDLR−/− cells rescued the deficient LDL clearance of LDLR−/− cells. In summary, ANGPTL3 deficiency in the presence of functional LDLR leads to the production of fewer lipoprotein particles due to early presecretory defects in particle assembly that are associated with adaptive changes in intrahepatic lipid metabolism. In contrast, when LDLR is absent, ANGPTL3 deficiency is associated with late presecretory regulation of ApoB100 degradation without impaired secretion. Our findings therefore suggest an unanticipated intrahepatic role for ANGPTL3, whose function varies with LDLR status.

Abstract The early effects of progressive collapsing foot deformity (PCFD) on the ankle and syndesmotic joints have not been three-dimensionally quantified. This case-control study focused on using weight bearing CT (WBCT) distance (DM) and coverage maps (CM) and volumetric measurements as 3D radiological markers to objectively characterize early effects of PCFD on the ankle and syndesmotic joints. Seventeen consecutive patients with symptomatic stage I flexible PCFD and 20 matched controls that underwent foot/ankle WBCT were included. Three-dimensional DM and CM of the ankle and syndesmotic joints, as well volumetric assessment of the distal tibiofibular syndesmosis was performed as possible WBCT markers of early PCFD. Measurements were compared between PCFD and controls. Significant overall reductions in syndesmotic incisura distances were observed in PCFD patients when compared to controls, with no difference in the overall syndesmotic incisura volume at 1, 3, 5 and 10 cm proximally to the ankle joint. CMs showed significantly decreased articular coverage of the anterior regions of the tibiotalar joint as well as medial/lateral ankle joint gutters in PCFD patients. This study showed syndesmotic narrowing and decreased articular coverage of the anterior aspect of the ankle gutters and talar dome in stage I PCFD patients when compared to controls. These findings are consistent with early plantarflexion of the talus within the ankle Mortise, and absence of true syndesmotic overload in early PCFD, and support DM and CM as early 3D PCFD radiological markers.

Modern Orthodoxy is a sect of Judaism which aims to combine a high level of commitment to Jewish observance with immersion in modern society. Alumni of Modern Orthodox parochial high schools have varying degrees of commitment towards religion. This study was designed to better understand the factors that lead adolescents towards internalizing traditional Orthodox beliefs. Previous studies on religion in general are lacking in quality and depth, using superficial factors such as church attendance to attest to religious commitment. Studies on Modern Orthodox Jewish teens are limited in quantity, with very few studies published on this population. This study focused on 1341 students from 18 Modern Orthodox high schools in the United States using the JewBALE 2.0 to collect the data. The design evaluated the relationship between spirituality and self-esteem, spiritual struggle, religious homogeny between parents and adolescents, and gender. Factors such as mental health, positive Judaic studies experience, and relationships with Judaic studies teachers were examined as potential mediators. The data indicated that students with high levels of spirituality would also have high levels of self-esteem and religious homogeny with their parents, as well as high levels of agreement with the Orthodox communal norms. Positive relationships with teachers and experiences in Jewish studies classes mediated the otherwise negative relationship between spirituality and disagreement with communal norms. Females were more likely to have high levels of spirituality than males. This study is important for those who want to better understand the factors involved in helping students enrolled in Jewish Modern Orthodox high schools achieve high levels of spirituality.

Objectives: We developed a questionnaire-based risk-scoring system to identify children at risk for rheumatic heart disease (RHD) in rural India. The resulting predictive model was validated in Nepal, in a population with a similar demographic profile to rural India. Methods: The study involved 8646 students (mean age 13.0 years, 46% boys) from 20 middle and high schools in the West Midnapore district of India. The survey asked questions about the presence of different signs and symptoms of RHD. Students with possible RHD who experienced sore throat and joint pain were offered an echocardiogram to screen for RHD. Their findings were compared with randomly selected students without these symptoms. The data were analyzed to develop a predictive model for identifying RHD. Results: Based on our univariate analyses, seven variables were used for building a predictive model. A four-variable model (joint pain plus sore throat, female sex, shortness of breath, and palpitations) best predicted the risk of RHD with a C-statistic of 0.854. A six-point scoring system developed from the model was validated among similarly aged children in Nepal. Conclusions: A simple questionnaire-based predictive instrument could identify children at higher risk for this disease in low-income countries where RHD remains prevalent. Echocardiography could then be used in these high-risk children to detect RHD in its early stages. This may support a strategy for more effective secondary prophylaxis of RHD.

Abstract We present time‐correlated ultra‐high‐speed video camera and electromagnetic field measurements of the attachment processes in a natural negative cloud‐to‐ground stroke. The video camera frame exposure time and pixel resolution were 740 ns and 0.91 m/pixel, respectively. The common streamer zone (CSZ) was first observed 2.52 µs preceding the first frame showing the return stroke (RS) in progress, when the upward and downward leader‐tips were 9.8 m apart. In the next frame, the two leaders were observed to have propagated toward each other within the CSZ, with their tips being 0.91 m apart. Our observations show with unprecedented precision/clarity that (a) the slow front in the field waveform is associated with the CSZ, and (b) the “proper” start of the RS is marked by the onset of the fast transition in the field waveform which occurs at the completion of the attachment processes (when the upward and downward leaders have merged).

Abstract Background Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. Methods A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. Results In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p

Abstract Background Pulmonary artery hypertension (PAH) is a progressive disease that result in right heart dysfunction. Lung transplantation (LTx) improve survival in end-stage disease. The aim of this study is to assess heart recovery after LTx for patients with primary and secondary pulmonary hypertension. Methods We conducted a single center retrospective review for patients with primary and secondary PAH underwent LTx between the period of January 2015 and December 2020. Baseline characteristics and echocardiographic measures were assessed pre-operative and after 1 year follow-up. Survival comparison between primary and secondary PAH was estimated by Kaplan–Meier method. Results We identified 43 participants for the study. Among the participants, 11 case had primary PAH. Median age during transplant was 60 years (45.5, 65.5). Left atrium anterio-posterior dimensions, systolic right ventricle pressure tricuspid peal regurgitant velocity and severity of tricuspid regurgitation were found to be significantly improved post-operatively compared to pre-operative echocardiography (p value

ABSTRACT Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

Background: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis. Objectives: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications. Methods: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone. Results: Among patients taking nintedanib ( n = 107) or pirfenidone ( n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients [5.2%], p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients [5.7%], p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant. Conclusion: Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy

Background and Aims: Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events and, thus, may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C. Methods: We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient: first, the 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. Results: The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 2.6% of patients had a large discrepancy exceeding 2%; however, these were all patients with a 3-year probability exceeding >5% in both models. Conclusion: Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest.

ABSTRACT: As the worldwide prevalence of overweight and obesity continues to rise, so too does the urgency to fully understand mediating mechanisms, to discover new targets for safe and effective therapeutic intervention, and to identify biomarkers to track obesity and the success of weight loss interventions. In 2016, the American Heart Association sought applications for a Strategically Focused Research Network (SFRN) on Obesity. In 2017, 4 centers were named, including Johns Hopkins University School of Medicine, New York University Grossman School of Medicine, University of Alabama at Birmingham, and Vanderbilt University Medical Center. These 4 centers were convened to study mechanisms and therapeutic targets in obesity, to train a talented cadre of American Heart Association SFRN‐designated fellows, and to initiate and sustain effective and enduring collaborations within the individual centers and throughout the SFRN networks. This review summarizes the central themes, major findings, successful training of highly motivated and productive fellows, and the innovative collaborations and studies forged through this SFRN on Obesity. Leveraging expertise in in vitro and cellular model assays, animal models, and humans, the work of these 4 centers has made a significant impact in the field of obesity, opening doors to important discoveries, and the identification of a future generation of obesity‐focused investigators and next‐step clinical trials. The creation of the SFRN on Obesity for these 4 centers is but the beginning of innovative science and, importantly, the birth of new collaborations and research partnerships to propel the field forward.

Abstract BackgroundThe high-intensity focused electromagnetic field (HIFEM) procedure is an effective method for noninvasive toning and shaping of buttocks. ObjectivesTo investigate and compare the efficacy of simultaneous application of HIFEM procedure with radiofrequency (RF) heating vs HIFEM standalone procedure on the buttocks. MethodsSixty-seven subjects (21-67 years, BMI 16-34 kg/m2 ResultsData of 32 subjects from group A and 31 subjects from group B were reviewed at 1-month follow-up. On average, subjects from group A showed a 31.3% higher increase in muscle thickness, as shown in the MRI evaluation. The gluteal muscle thickness continued to grow and peaked at a 3-month follow-up, wherein 27 patients were evaluated in each group (n ConclusionsOur results suggest that simultaneous use of HIFEM + RF is safe and significantly more effective for gluteal contouring than the HIFEM procedure alone. Level of Evidence: 2

Abstract Aims The Fontan operation has resulted in improved survival in patients with single‐ventricle congenital heart disease. As a result, there is a growing population of teenagers and adults with a Fontan circulation. Many co‐morbidities have been increasingly recognized in this population due to the unique features of the Fontan circulation. Standardization of how Fontan co‐morbid conditions are defined will help facilitate understanding, consistency and interpretability of research and clinical experience. Unifying common language usage in Fontan is a critical precursor step for data comparison of research findings and clinical outcomes and ultimately accelerating improvements in management for this growing group of patients. This manuscript aimed to create unified definitions for morbidities seen after the Fontan palliation. Methods In association of many congenital heart disease organizations, this work used Delphi methodology to reach a broad consensus among recognized experts regarding commonly used terms in Fontan care and research. Each definition underwent at least three rounds of revisions to reach a final definition through surveys sent to experts in the field of single‐ventricle care. Results The process of reaching a consensus on multiple morbidities associated with the Fontan procedure is summarized in this manuscript. The different versions that preceded reaching the consensus are also presented in the Supporting Information. Table 1 represents the final definitions according to the consensus. Conclusions We propose the use of these definitions for clinical care, future research studies, registry development and clinical trials.

Category: Ankle Arthritis Introduction/Purpose: Despite the increasing numbers of ankle replacements that are being performed there are still limited studies on the survival of ankle replacements and which factors influence survivorship comparisons between different implants. The primary aim of this study is to link NJR data with NHS digital data to determine the true failure rates of ankle replacements and to determine the risk factors for failure of total ankle replacements Methods: A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as the removal or exchange of any components of the implanted device inserted during ankle replacement surgery. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates. Results: 5,562 primary ankle replacement were recorded on the NJR between 1st April 2010 and 31st December 2018. The unadjusted 1-year survivorship of ankle replacements was 98.8% (95% CI 98.4%-99.0the 5-year survival in 2725 patients was 90.2% (95% CI 89.2%-91.1) and the 10-year survival in 199 patients was 86.2% (95% CI 84.6%-87.6%). In univariate cox regression models age, BMI, ASA, Charlson co-morbidity score, indication for surgery were significantly associated with an increased risk of failure. In multivariate cox regression models only age (HR 0.956, 95% CI 0.942-0.970), BMI (HR 1.032, 95% CI 1.006-1.059) and indication (HR 0.880, 95% CI 0.799-0.968) were associated with an increased risk of failure. Conclusion: Ankle replacements have been demonstrated to have higher failure rates in younger patients, those with an increased BMI, and those with osteoarthritis. These findings should be taken into account when deciding which patients should undergo an ankle replacement and in counselling them on the likely survivorship of their ankle replacement

Category: Ankle Arthritis Introduction/Purpose: Total talus replacements have been proposed as a method to treat talar AVN replacing the entire talus. The potential for total talar replacements has increased with the advent of patient specific implants utilising 3D printing based on CT scanning of the ipsilateral or contralateral talus. The primary aim of this systematic review is to analyse the current literature on total talus replacements. It specifically aims to look at the indications, complications, survival and functional outcomes. Methods: A systematic review was undertaken including all levels of evidence and following PRISMA guidelines. Basic percentages and a weighted pooled proportion for failures using the Freeman Tukey double arscine transformation were performed. Results: 9 papers with 151 patients were included. The mean age ranged from 27.6 to 72, with 5 papers having a mean age of less than 50. Mean follow-up ranged from 12.8 to 58 months. The most common indication was avascular necrosis in 103 patients.4 studies used 3D printing and 5 customised implants. 3 studies undertook a talus replacement with an ankle replacement. 4 studies used ceramic prostheses, 3 cobalt chromium 1 stainless steel and 1 titanium with ceramic surface. Post-operative complications ranged from 0 to 33%. 69.6% of 23 functional outcomes scores demonstrated significant improvement in functional scores with the others demonstrating a non-significant improvement.3 of 151 implants failed requiring further surgery with 2 revisions and 1 amputation. 6 of the 8 studies did not report any operations for failure. The cumulative incidence of failure was 0.1 % (95% CI 0.0- 4.9%). Conclusion: Total talus replacements are a potential alternative to tibiotalocalcaneal fusion for patients with avascular necrosis of the talus. Further studies are required to ensure good outcomes prior to an increase in use of this prosthesis.

Category: Ankle Arthritis Introduction/Purpose: There are limited studies on the outcomes of conversion to fusion following a failed ankle replacement. The primary aim of this NJR data linkage study is to determine the outcomes of conversion to fusion following a failed ankle replacement. Methods: A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as a further fusion procedure or amputation. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates. Results: 131 patients underwent conversion to fusion. The mean time from primary replacement was 33.8 months (range 1-100). The mean age was 63.3 (range 33-85), there were 73 males (55.7%). The mean BMI was 30.7 (SD 5.3) mean ASA was 2.0 and the mean Charlson co-morbidity score was 2.5. The most commonly revised implant was the Mobility in 45.0%, Zenith in 16.8% and Box in 11.5%.105 (80.2%) were as a single stage and 26 (19.8%) as a 2 stage procedure. The 1 year survivorship was 96.0% (95% CI 90.6%-98.3%), 2 year survivorship was 83.8% (95% CI 75.4%-89.5%) and 5 year survivorship was 72.4% (95% CI 62.0%-80.4%) A Cox regression model adjusting for individual factors did not find any risk factor significantly increased the risk of failure. Conclusion: Conversion to fusion following a failed ankle replacement has high rates of further surgery. Further prospective studies are required to determine risk factors for failure to improve outcomes for these patients.

Category: Ankle Arthritis; Ankle; Hindfoot; Other Introduction/Purpose: End-stage ankle osteoarthritis (EOA) causes severe pain and chronic disability. Once non operative measures have been exhausted the two main surgical treatments include total ankle replacement (TAR) and ankle fusion (AF). Systematic reviews have confirmed that both procedures are effective but there has never been a robust randomised multicentre level I study comparing the two treatments. Our objective was to investigate and compare the clinical and cost effectiveness of TAR against AF in the treatment of end-stage ankle osteoarthritis in patients aged 50-85 years. Methods: TARVA is a multi-centre, parallel-group, open label randomised trial. Patients with EOA, aged 50-85, suitable for either procedure were recruited at 17 UK hospitals. Randomisation was carried out using a secure on-line service and was stratified by surgeon and the presence or absence of adjacent joint OA (based on an independently reviewed preoperative MRI scan). Participants were randomised 1:1 to either TAR or ankle arthrodesis. The primary outcome was the change in the Manchester Oxford Foot & Ankle Questionnaire (MOXFQ) walking/standing domain scores between pre-operation and 52 weeks post- operation. Secondary outcomes measures included FAAM; FAAM (ADL); and Sport subscale scores. Quality of life was measured using the EQ-5D-5L. Total range of tibia to floor motion was measured using a validated method. Health economic analysis used mean incremental cost per quality-adjusted life years (QALY) gained. Analysis was by intention to treat. The trial registration is ISRCTN60672307. Results: Of 933 eligible patients 303 were randomised. 282 underwent surgery. Mean age 68 (71% male). Aetiology was post- trauma in 55.3%, and inflammatory in 7.1%. Groups were well balanced at baseline on all parameters. 54% TARs were fixed bearing. 61% of fusions were performed arthroscopically. At 2 years the adjusted mean difference in the change in MOXFQ W/S between TAR & AF was -4.4(95% CI -11.38 to 2.68, p=0∙23). Post hoc analysis of the commonest implant type (fixed bearing TAR) did show a statistically significant improvement over AF (p=0∙04, -8.9, 95% CI -17.2 to -0.6). Secondary outcomes, EQ5D-VAS and FAAM were significant. Complications included wound healing issues (13.8% vs 5.5%); nerve injuries (4.3% vs 0.7%). 11.8% of AF patients had plain radiographic evidence of non-union but only 6.9% had symptoms. Reoperation rate was 7.2% for TAR vs 5.2% for AF; and revision rate was 0.7% for TAR vs 2.8% for AF. Conclusion: Patients improved in all outcomes in both arms. We did not show a significant difference in our primary outcome measure between TAR and AF overall(p=0.23), but did show significance when fixed bearing TAR alone was compared against AF(p=0.04). Secondary outcomes did show significance. Adjacent joint arthritis increases the size of effect noted between arms. There were more wound healing issues and nerve injuries in TAR group. The symptomatic non-union rate for AF is 6.9%. TAR is likely to be cost-effective compared to AF at the NICE cost-effectiveness threshold of £20,000 per Quality Adjusted Life Year gained over the patients' lifetime.

Lipid accumulation in nonadipose tissues can cause lipotoxicity, leading to cell death and severe organ dysfunction. Adipose triglyceride lipase (ATGL) deficiency causes human neutral lipid storage disease and leads to cardiomyopathy; ATGL deficiency has no current treatment. One possible approach to alleviate this disorder has been to alter the diet and reduce the supply of dietary lipids and, hence, myocardial lipid uptake. However, in this study, when we supplied cardiac Atgl KO mice a low- or high-fat diet, we found that heart lipid accumulation, heart dysfunction, and death were not altered. We next deleted lipid uptake pathways in the ATGL-deficient mice through the generation of double KO mice also deficient in either cardiac lipoprotein lipase or cluster of differentiation 36, which is involved in an lipoprotein lipase-independent pathway for FA uptake in the heart. We show that neither deletion ameliorated ATGL-deficient heart dysfunction. Similarly, we determined that non-lipid-containing media did not prevent lipid accumulation by cultured myocytes; rather, the cells switched to increased de novo FA synthesis. Thus, we conclude that pathological storage of lipids in ATGL deficiency cannot be corrected by reducing heart lipid uptake.

Measurement(s) tau neutrino Technology Type(s) detector Sample Characteristic - Environment neutrino beam Sample Characteristic - Location Laboratori Nazionali del Gran Sasso Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14979858

CD36 mediates the uptake of long-chain fatty acids (FAs), a major energy substrate for the myocardium. Under excessive FA supply, CD36 can cause cardiac lipid accumulation and inflammation while its deletion reduces heart FA uptake and lipid content and increases glucose utilization. As a result, CD36 was proposed as a therapeutic target for obesity-associated heart disease. However, more recent reports have shown that CD36 deficiency suppresses myocardial flexibility in fuel preference between glucose and FAs, impairing tissue energy balance, while CD36 absence in tissue macrophages reduces efferocytosis and myocardial repair after injury. In line with the latter homeostatic functions, we had previously reported that CD36–/– mice have chronic subclinical inflammation. Lipids are important for the maintenance of tissue homeostasis and there is limited information on heart lipid metabolism in CD36 deficiency. Here, we document in the hearts of unchallenged CD36–/– mice abnormalities in the metabolism of triglycerides, plasmalogens, cardiolipins, acylcarnitines, and arachidonic acid, and the altered remodeling of these lipids in response to an overnight fast. The hearts were examined for evidence of inflammation by monitoring the presence of neutrophils and pro-inflammatory monocytes/macrophages using the respective positron emission tomography (PET) tracers, 64Cu-AMD3100 and 68Ga-DOTA-ECL1i. We detected significant immune cell infiltration in unchallenged CD36–/– hearts as compared with controls and immune infiltration was also observed in hearts of mice with cardiomyocyte-specific CD36 deficiency. Together, the data show that the CD36–/– heart is in a non-homeostatic state that could compromise its stress response. Non-invasive immune cell monitoring in humans with partial or total CD36 deficiency could help evaluate the risk of impaired heart remodeling and disease.

Voisin et al. show that reducing phosphorylation at serine 196 of LXRα (LXRα pS196) in hematopoietic cells attenuates atherosclerosis and obesity of mice fed a high-fat diet. They find that the transcriptional activity of LXRα is reprogrammed in macrophages and T cells to promote an anti-inflammatory phenotype, thus identifying a functional role of LXRα pS196 in immune cells.

Abstract Background Recognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making. Methods Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients. Results After a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting. Conclusions The guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.

The LDL receptor-related protein 1 (LRP1) partakes in metabolic and signaling events regulated in a tissue-specific manner. The function of LRP1 in airways has not been studied. We aimed to study the function of LRP1 in smoke-induced disease. We found that bronchial epithelium of patients with chronic obstructive pulmonary disease and airway epithelium of mice exposed to smoke had increased LRP1 expression. We then knocked out LRP1 in human bronchial epithelial cells in vitro and in airway epithelial club cells in mice. In vitro, LRP1 knockdown decreased cell migration and increased transforming growth factor β activation. Tamoxifen-inducible airway-specific LRP1 knockout mice (club Lrp1−/−) induced after complete lung development had increased inflammation in the bronchoalveolar space and lung parenchyma at baseline. After 6 months of smoke exposure, club Lrp1−/− mice showed a combined restrictive and obstructive phenotype, with lower compliance, inspiratory capacity, and forced expiratory volume0.05/forced vital capacity than WT smoke-exposed mice. This was associated with increased values of Ashcroft fibrotic index. Proteomic analysis of room air exposed-club Lrp1−/− mice showed significantly decreased levels of proteins involved in cytoskeleton signaling and xenobiotic detoxification as well as decreased levels of glutathione. The proteome fingerprint created by smoke eclipsed many of the original differences, but club Lrp1−/− mice continued to have decreased lung glutathione levels and increased protein oxidative damage and airway cell proliferation. Therefore, LRP1 deficiency leads to greater lung inflammation and damage and exacerbates smoke-induced lung disease.

Category: Hindfoot; Midfoot/Forefoot Introduction/Purpose: Peritalar subluxation (PTS) of the hindfoot is a critical finding in Progressive Collapsing Foot Deformity (PCFD). Subluxation of the middle facet and sinus tarsi recently been shown to represent essential markers of pronounced and potentially progressive deformity. Weightbearing CT (WBCT) imaging and three-dimensional (3D) distancing coverage maps (CM) allow a complete and accurate assessment of PTS markers across the entire peritalar surface. This prospective comparative study aimed to assess the effectiveness of joint-sparing realignment surgical treatment for flexible PCFD in reducing PTS and to correlate the improvement with patient-reported outcomes (PROs). We hypothesized that would significantly improve PTS markers, mainly decreasing sinus tarsi coverage/impingement and middle facet subluxation, and that this improvement would correlate with increased PROs. Methods: In this IRB-approved prospective and comparative study, we enrolled patients with flexible PCFD, no prior surgeries, and failed conservative treatment. Included females/3 males, mean age 57.2, range 37-74) underwent joint-sparing surgical realignment procedure by a single surgeon. Standing weightbearing CT (WBCT) was complete 3-months postoperatively. Following automatic bone segmentation, 3D distance maps (DMs) of the entire peritalar surface were generated, and coverage of the subtalar joint (anterior, middle, and posterior) and sinus tarsi were assessed as markers of PTS. Joint coverage was defined as the percentage of articular space where DMs were

The Fontan or Fontan Kreutzer procedure is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease, offering the potential for survival and good quality of life well into adulthood. As more patients with Fontan circulation age, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse hemodynamics and presenting weeks to years after Fontan surgery. The causes are not well understood, but likely include a combination of lymphatic insufficiency, high central venous pressure, loss of heparan sulfate from intestinal epithelial cells, abnormal mesenteric circulation, and intestinal inflammation. A comprehensive evaluation including multimodality imaging and cardiac catheterization is necessary to diagnose and treat any reversible causes. In advanced cases, early referral for heart transplantation evaluation or lymphatic decompression procedures (if the single ventricle function remains adequate) is indicated. Despite the improvement in detection and management options, the mortality remains high. Standardization of protein-losing enteropathy definition and management strategies will help facilitate interpretation of research and clinical experience, potentially fostering the identification of new therapies. Based on the published data, this review suggests a standardized approach to diagnosis and treatment.

Abstract Background Vietnam has been experiencing an epidemiologic transition to that of a lower-middle income country with an increasing prevalence of non-communicable diseases. The key risk factors for cardiovascular disease (CVD) are either on the rise or at alarming levels in Vietnam, particularly hypertension (HTN). Inasmuch, the burden of CVD will continue to increase in the Vietnamese population unless effective prevention and control measures are put in place. The objectives of the proposed project are to evaluate the implementation and effectiveness of two multi-faceted community and clinic-based strategies on the control of elevated blood pressure (BP) among adults in Vietnam via a cluster randomized trial design. Methods Sixteen communities will be randomized to either an intervention (8 communities) or a comparison group (8 communities). Eligible and consenting adult study participants with HTN (n = 680) will be assigned to intervention/comparison status based on the community in which they reside. Both comparison and intervention groups will receive a multi-level intervention modeled after the Vietnam National Hypertension Program including education and practice change modules for health care providers, accessible reading materials for patients, and a multi-media community awareness program. In addition, the intervention group only will receive three carefully selected enhancements integrated into routine clinical care: (1) expanded community health worker services, (2) home BP self-monitoring, and (3) a “storytelling intervention,” which consists of interactive, literacy-appropriate, and culturally sensitive multi-media storytelling modules for motivating behavior change through the power of patients speaking in their own voices. The storytelling intervention will be delivered by DVDs with serial installments at baseline and at 3, 6, and 9 months after trial enrollment. Changes in BP will be assessed in both groups at several follow-up time points. Implementation outcomes will be assessed as well. Discussion Results from this full-scale trial will provide health policymakers with practical evidence on how to combat a key risk factor for CVD using a feasible, sustainable, and cost-effective intervention that could be used as a national program for controlling HTN in Vietnam. Trial registration ClinicalTrials.gov NCT03590691 . Registered on July 17, 2018. Protocol version: 6. Date: August 15, 2019.

Objectives: We examined the level of awareness about Rheumatic Heart Disease (RHD) among school-aged children in a rural district of India and evaluated the effects of a questionnaire-based survey in improving the level of awareness. Methods: The study involved 8,646 students aged 10–16 years from 20 schools in West Midnapore, India which was conducted in August 2017. We examined changes in the level of awareness of RHD using a 29-point scoring system in seven domains. The baseline questionnaire survey assessed students’ knowledge and was followed by a multimedia presentation about RHD and a post-intervention survey using the same questionnaire. The questionnaire included 9 questions on different aspects of RHD including prevalence, nature of disease, symptoms, determinants, treatment options, impact of the disease and diagnosis. Results: The mean age of the study population was 13 years and 46% were boys. At baseline, the mean level of knowledge about RHD was 42% (12.2 out of 29 points). After the school-based presentation, the score improved to a mean of 55% (15.9 points on the 29-point scale), a 31% relative improvement. Improvement in students' knowledge was noted across all seven domains, individually and combined (p

Abstract Background Holistic care models emphasize management of comorbid conditions to improve patient-reported outcomes in treatment of atrial fibrillation (AF). We investigated relations between multimorbidity, physical frailty, and self-rated health (SRH) among older adults with AF. Methods Patients (n = 1235) with AF aged 65 years and older were recruited from five medical centers in Massachusetts and Georgia between 2015 and 2018. Ten previously diagnosed cardiometabolic and 8 non-cardiometabolic conditions were assessed from medical records. Physical Frailty was assessed with the Cardiovascular Health Study frailty scale. SRH was categorized as either “excellent/very good”, “good”, and “fair/poor”. Separate multivariable ordinal logistic models were used to examine the associations between multimorbidity and SRH, physical frailty and SRH, and multimorbidity and physical frailty. Results Overall, 16% of participants rated their health as fair/poor and 14% were frail. Hypertension (90%), dyslipidemia (80%), and heart failure (37%) were the most prevalent cardiometabolic conditions. Arthritis (51%), anemia (31%), and cancer (30%), the most common non-cardiometabolic diseases. After multivariable adjustment, patients with higher multimorbidity were more likely to report poorer health status (Odds Ratio (OR): 2.15 [95% CI: 1.53–3.03], ≥ 8 vs 1–4; OR: 1.37 [95% CI: 1.02–1.83], 5–7 vs 1–4), as did those with more prevalent cardiometabolic and non-cardiometabolic conditions. Patients who were pre-frail (OR: 1.73 [95% CI: 1.30–2.30]) or frail (OR: 6.81 [95% CI: 4.34–10.68]) reported poorer health status. Higher multimorbidity was associated with worse frailty status. Conclusions Multimorbidity and physical frailty were common and related to SRH. Our findings suggest that holistic management approaches may influence SRH among older patients with AF.