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Gérard Reach,1 Laurent Benarbia,2 Pierre-Yves Benhamou,3 Brigitte Delemer,4 Séverine Dubois,5 Didier Gouet,6 Bruno Guerci,7 Nathalie Jeandidier,8 Karim Lachgar,9 Gilles Le Pape,10 Rémy Leroy,11 Jean-Hugues Masgnaux,12 Philippe Raclet,13 Yves Reznik,14 Jean-Pierre Riveline,15,16 Pauline Schaepelynck,17 Anne Vambergue,18 Bruno Vergès19 1Health Education and Promotion Laboratory (LEPS EA 3412), Sorbonne Paris Nord University, Bobigny, France; 2Marketing Studio, Paris, France; 3Department of Endocrinology, Grenoble University Hospital; Grenoble Alpes University, INSERM U1055, LBFA, Grenoble, France; 4Service d’Endocrinologie – Diabète – Nutrition, CHU de Reims - Hôpital Robert Debré, and Université de Reims Champagne Ardenne, UFR Sciences Exactes Et Naturelles, Reims, France; 5Department of Diabetology and Endocrinology, CHU Angers, Angers, France; 6Department of Diabetology and Endocrinology, Saint Louis Hospital, La Rochelle, France; 7Department of Endocrinology, Diabetology and Nutrition, CHRU of Nancy, Brabois Hospital, and ILCV Lorraine University, Vandoeuvre-les-Nancy, France; 8Department of Endocrinology, Diabetes and Nutrition, Hôpitaux Universitaires de Strasbourg, and Université de Strasbourg, Strasbourg, France; 9Department of Diabetology and Endocrinology, Centre Hospitalier Simone Veil, Eaubonne, France; 10General Practice, Penmarc’h, France; 11Private Medical Practice, Endocrinology and Diabetology, Lille, France; 12M&M Conseil, Boulogne, France; 13Association Française des Diabétiques de Bourgogne Franche-Comté, Dijon, France; 14Department oEndocrinology and Diabetology, CHU Côte de Nacre, Caen, and University of Caen Basse-Normandie, Medical School, Caen, France; 15Department of Diabetology and Endocrinology, Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France; 16Unité INSERM U1138 Immunity and Metabolism in Diabetes, ImMeDiab Team, Centre de Recherches des Cordeliers, and Université de Paris, Paris, France; 17Department of Nutrition-Endocrinology-Metabolic Diseases, Pôle ENDO, APHM-Hôpital la Conception, Marseille, France; 18Department of Diabetology, Endocrinology, Metabolism and Nutrition, CHU Lille, and University Hospital European Genomic Institute for Diabetes, Lille, France; 19Department of Endocrinology-Diabetology,CHU Dijon, and University of Burgundy, INSERM LNC UMR1231, Dijon, FranceCorrespondence: Gérard Reach, Health Education and Promotion Laboratory (LEPS EA 3412), Sorbonne Paris Nord University, 74 Rue Marcel Cachin, Bobigny Cedex, 93017, France, Tel + 33 (0)6 60 84 53 25, Email gerardreach@icloud.comBackground: Support programs are provided to people with diabetes to help them manage their disease. However, adherence to and persistence in support programs are often low, making it difficult to demonstrate their effectiveness.Aim: To identify the determinants of patients’ perceived interest in diabetes support programs because it may be a powerful determinant of effective participation in such programs.Patients and Methods: An online study conducted in April 2021 in metropolitan France on 600 people with diabetes recruited from a consumer panel. A 64-item psychosocial questionnaire including a question asking to evaluate the helpfulness of a support program was used. Univariate, multivariate, and multiple correspondence analyses were performed.Results: The existence of a typology, known as Unsafe/Safe, was discovered, in which patients with type 2 diabetes respond in two distinct ways. Type U (unsafe) patients, who believe that a support program would be helpful, are more likely to be nonadherent to their treatment, have high hemoglobin A1c levels, have at least one diabetic complication, lack information regarding their disease and treatment, rate the burden of their disease and impairment of their quality of life as high, worry about their future, and are pessimistic. Type S (safe) patients have the opposite characteristics. Type U patients can be dichotomized into two broad classes: one in which they lack information regarding disease and treatment and the other in which alterations in the quality of life and burden of the disease predominate. Insulin-treated patients give more importance to the lack of information, whereas noninsulin-treated patients complain primarily about the burden of the disease and impairment of quality of life.Conclusion: This study describes this new U/S typology, proposes a simple method based on a nine-item questionnaire to identify type U patients by calculating a Program Helpfulness Score described herein, and clarifies the nature of the intervention to be provided to them. This novel approach could be applied to other chronic diseases.Keywords: type 2 diabetes, adherence, support programs, typology, personality traits, clinical outcomes, patients’ expectations

Abstract Background Public health concern over college students mixing caffeine-containing energy drinks (EDs) and alcohol has contributed to an array of ED-focused research studies. One review found consistent associations between ED use and heavy/problem drinking as well as other drug use and risky behaviors (Nutr Rev 72:87–97, 2014). The extent to which similar patterns exist for other sources of caffeine is not known. The present study examined associations between coffee and ED consumption and alcohol, tobacco and other drug use; alcohol use problems; and parental substance abuse and mental health problems in a sample of college freshmen. Methods Subjects were N = 1986 freshmen at an urban university who completed an on-line survey about demographics; caffeine; alcohol, tobacco and other drug use; and family history. The sample was 61% female and 53% White. Chi-square analyses and multivariable binary or ordinal logistic regression were used to compare substance use, problem alcohol behavior, and familial risk measures across 3 caffeine use groups: ED (with or without Coffee) (ED + Co; N = 350); Coffee but no ED (Co; N = 761); and neither coffee nor ED (NoCE; N = 875) use. Results After adjusting for gender and race, the 3 caffeine use groups differed on 8 of 9 symptoms for alcohol dependence. In all cases, the ED + Co group was most likely to endorse the symptom, followed by the Co group and finally the NoCE group (all p

Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants (

Background: Recent literature suggests that state-level legislation is effective in reducing postoperative opioid prescribing after total joint arthroplasty but has not addressed the effect on opioid antagonist coprescribing. This study aims to describe the change in postoperative opioid and opioid antagonist prescribing patterns after total joint arthroplasty following passage of state-level opioid-limiting legislation and to determine the comorbidities associated with increased opioid prescribing in this population. Methods: Billing data were used to identify all patients who underwent primary total hip or knee arthroplasty admitted between March 2016 and March 2018 at our institution. The data were divided into 2 cohorts comprising the year before (671 subjects) and after (713 subjects) the legislation. Discharge prescriptions were reviewed, and the median morphine milligram equivalents (MME) per day and naloxone prescriptions were recorded. International Classification of Diseases codes were used to identify comorbid conditions of interest present during previous inpatient or outpatient encounters. Results: There was a significant reduction in both the minimum and maximum median MME per day after introduction of state legislation and a substantial increase in opioid antagonist coprescription. Total knee arthroplasty, younger age, male sex, chronic pain disorders, post-traumatic stress disorder, and prior opioid abuse were correlated with increased opioid prescribing. Conclusion: Our findings suggest that state-level legislation is effective in decreasing the MME per day prescribed and increasing opioid antagonist coprescription in the postoperative period for patients undergoing total hip and knee arthroplasties at our institution. These changes may lead to a decrease in opioid-related morbidity and mortality in the patient population undergoing total hip and knee arthroplasties.

A nontargeted plasma metabolomic analysis was conducted to compare differentially expressed metabolites in women with and without fibromyalgia (FM) using data and samples collected from two parent studies in women with FM (n = 20) and comparative data collected from newly recruited age‐matched women (n = 20). Blood plasma samples were analyzed for metabolite content using liquid chromatography mass spectrometry. Consolidation of positive and negative ion mode metabolomics data with fold change (>2 or

Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more indirect pathways through neuroinflammation, both of which can be worsened by opioid co-exposure. To assess whether excitotoxicity and/or neuroinflammation might drive depressive behaviors in persons infected with HIV (PWH) and those who use opioids, male mice were exposed to HIV-1 Tat for eight weeks, given escalating doses of morphine during the last two weeks, and assessed for depressive-like behavior. Tat expression decreased sucrose consumption and adaptability, whereas morphine administration increased chow consumption and exacerbated Tat-induced decreases in nesting and burrowing—activities associated with well-being. Across all treatment groups, depressive-like behavior correlated with increased proinflammatory cytokines in the PFC. Nevertheless, supporting the theory that innate immune responses adapt to chronic Tat exposure, most proinflammatory cytokines were unaffected by Tat or morphine. Further, Tat increased PFC levels of the anti-inflammatory cytokine IL-10, which were exacerbated by morphine administration. Tat, but not morphine, decreased dendritic spine density on layer V pyramidal neurons in the anterior cingulate. Together, our findings suggest that HIV-1 Tat and morphine differentially induce depressive-like behaviors associated with increased neuroinflammation, synaptic losses, and immune fatigue within the PFC.

RVA Breathes, a community program to improve asthma management and care coordination among children living in a low-income, urban area, is being evaluated in a randomized clinical trial. In March 2020, RVA Breathes was converted to a remote program due to the COVID-19 pandemic; this report provides an update on the modifications made to the RVA Breathes trial. Additionally, given that families in the program have been disproportionally impacted by both COVID-19 and significant social unrest at both the local and national level, strategies used to enroll and engage families in the trial who bore disproportionately high burdens during this time period are outlined. Remote sessions (telephone or video) for families enrolled in the program prior to the onset of COVID-19 began in April 2020; enrollment of new families began remotely in July 2020 using adapted consent procedures. Baseline, intervention, and follow-up sessions were delivered either via the telephone or video depending upon family preference. Strategies were implemented to engage caregivers and children in completing measures over the telephone or video versus in person. Tangible intervention materials and participant payments were dropped off at family homes using contactless procedures. Our team was able to adapt and safely continue a large, community-based clinical trial, despite the increased health risks and social isolation mandates from the pandemic, by transitioning to a remote format. Challenges remain in determining whether RVA Breathes as a remote program has had the same impact on child asthma as the face-to-face interventions that comprised its original format.

Abstract Background Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies like rheumatoid factor (RF), anti-cyclic citrullinated peptide-2 (anti-CCP2), and anti-carbamylated protein (anti-CarP) antibodies. It is currently unclear whether changes in autoantibody levels are associated with disease activity/treatment outcomes and whether they are modified by treatment intensity. Therefore, we determined longitudinal changes in RA-autoantibody levels, the association between these changes and activity score (DAS) and treatment outcomes, and the effect of intensity of immunosuppressive treatment on levels. Methods In 381 seropositive RA patients from the IMPROVED study, we measured IgG, IgM, and IgA of anti-CCP2 and anti-CarP; IgM and IgA of RF; and IgG against four citrullinated and two acetylated peptides at 4-month intervals over the first year of treatment. Following initial prednisone and methotrexate (MTX), treatment was changed every 4 months aiming for DAS

Abstract Background While therapy services may start in the Neonatal Intensive Care Unit (NICU) there is often a gap in therapy after discharge. Supporting Play Exploration and Early Development Intervention (SPEEDI) supports parents, helping them build capacity to provide developmentally supportive opportunities starting in the NICU and continuing at home. The purpose of this single blinded randomized pilot clinical trial was to evaluate the initial efficacy of SPEEDI to improve early reaching and exploratory problem solving behaviors. Methods Fourteen infants born very preterm or with neonatal brain injury were randomly assigned to SPEEDI or Usual Care. The SPEEDI group participated in 5 collaborative parent, therapist, and infant interventions sessions in the NICU (Phase 1) and 5 at home (Phase 2). Parents provided daily opportunities designed to support the infants emerging motor control and exploratory behaviors. Primary outcome measures were assessed at the end of the intervention, 1 and 3 months after the intervention ended. Reaching was assessed with the infant supported in an infant chair using four 30 s trials. The Early Problem Solving Indicator was used to evaluate the frequency of behaviors during standardized play based assessment. Effect sizes are including for secondary outcomes including the Test of Infant Motor Performance and Bayley Scales of Infant and Toddler Development. Results No group differences were found in the duration of toy contact. There was a significant group effect on (F1,8 = 4.04, p = 0.08) early exploratory problem-solving behaviors with infants in the SPEEDI group demonstrating greater exploration with effect sizes of 1.3, 0.6, and 0.9 at the end of the intervention, 1 and 3 months post-intervention. Conclusions While further research is needed, this initial efficacy study showed promising results for the ability of SPEEDI to impact early problem solving behaviors at the end of intervention and at least 3 months after the intervention is over. While reaching did not show group differences, a ceiling effect may have contributed to this finding. This single blinded pilot RCT was registered prior to subject enrollment on 5/27/14 at ClinicalTrials.Gov with number NCT02153736.

ABSTRACT HIV causes neurodegeneration and dementia in AIDS patients, but its function in milder cognitive impairments in virologically suppressed patients on antiretroviral therapy is unknown. Such patients are immunocompetent, have low peripheral and brain HIV burdens, and show minimal brain neuropathology. Using the model of HIV-related memory impairment in EcoHIV-infected conventional mice, we investigated the neurobiological and cognitive consequences of efficient EcoHIV expression in the mouse brain after intracerebral infection. HIV integrated and persisted in an expressed state in brain tissue, was detectable in brain monocytic cells, and caused neuroinflammatory responses and lasting spatial, working, and associative memory impairment. Systemic antiretroviral treatment prevented direct brain infection and memory dysfunction indicating the requirement for HIV expression in the brain for disease. Similarly inoculated murine leukemia virus used as a control replicated in mouse brain but not in monocytic cells and was cognitively benign, linking the disease to HIV-specific functions. Memory impairment correlated in real time with hippocampal dysfunction shown by defective long-term potentiation in hippocampal slices ex vivo and with diffuse synaptodendritic injury in the hippocampus reflected in significant reduction in microtubule-associated protein 2 and synapsin II staining. In contrast, there was no evidence of overt neuronal loss in this region as determined by neuron-specific nuclear protein quantification, TUNEL assay, and histological observations. Our results reveal a novel capacity of HIV to induce neuronal dysfunction and memory impairment independent of neurotoxicity, distinct from the neurotoxicity of HIV infection in dementia. IMPORTANCE HIV neuropathogenesis has been attributed in large measure to neurotoxicity of viral proteins and inflammatory factors produced by infected monocytic cells in the brain. We show here that HIV expression in mouse brain causes lasting memory impairment by a mechanism involving injury to hippocampal synaptodendritic arbors and neuronal function but not overt neuronal loss in the region. Our results mirror the observation of minimal neurodegeneration in cognitively impaired HIV patients on antiretroviral therapy and demonstrate that HIV is nonneurotoxic in certain brain abnormalities that it causes. If neurons comprising the cognition-related networks survive HIV insult, at least for some time, there is a window of opportunity for disease treatment.

BackgroundCirrhosis can alter several metabolic pathways. Metabolomics could prognosticate outcomes like hepatic encephalopathy (HE), transplant, hospitalization and death.AimDetermine changes in serum and urine metabolomics in cirrhotics who develop outcomes.MethodsCirrhotic outpatients underwent data, serum/urine collection and were followed for 90 days. Demographics, cirrhosis details and medications were collected. Metabolomics was performed on urine/serum using GC/MS with subsequent bioinformatics analyses (ChemRICH, MetaMAPP and PLS-DA). Logistic regression adjusting for covariates (demographics, alcohol etiology, prior HE, PPI, SBP prophylaxis, rifaximin/lactulose) were performed and ROC curves comparing MELD to adjusted serum & urine metabolites were created.Results211 patients gave serum, of which 64 were hospitalized, 19 developed HE, 13 were transplanted and 11 died. 164 patients gave urine of which 56 were hospitalized, 18 developed HE, 12 were transplanted and 11 died. Metabolomics: Saturated fatty acids, amino acids and bioenergetics-related metabolites differentiated patients with/without outcomes. After regression, 232, 228, 284 and 229 serum metabolites were significant for hospitalization, HE, death and transplant. In urine 290, 284, 227 & 285 metabolites were significant for hospitalization, HE, death and transplant respectively. AUC was higher for serum metabolites vs MELD for HE (0.85 vs.0.76), death (0.99 vs.0.88), transplant (0.975 vs.0.94) and hospitalizations (0.84 vs.0.83). Similarly, urinary metabolite AUC was also higher than MELD for HE (0.87 vs.0.72), death (0.92 vs 0.86), transplant (0.99 vs.0.90) and hospitalizations (0.89 vs.0.84).ConclusionsIn this exploratory study, serum and metabolites focused on lipid, bioenergetics and amino acid metabolism are altered in cirrhotics who develop negative outcomes.

Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O2 every 90 s) and sustained hypoxia (SH; 10% O2) during sleep for up to 14 days on the induction of nitric oxide synthase (NOS) isoforms in the brain were examined in the cortex of Sprague–Dawley rats. No significant changes of endothelial NOS (eNOS) and neuronal NOS (nNOS) occurred over time with either IH or SH. Similarly, inducible NOS (iNOS) was not affected by SH. However, increased expression and activity of iNOS were observed on days 1 and 3 of IH (P < 0.01 vs. control; n = 12/group) and were followed by a return to basal levels on days 7 and 14. Furthermore, IH-mediated neurobehavioral deficits in the water maze were significantly attenuated in iNOS knockout mice. We conclude that IH is associated with a time-dependent induction of iNOS and that the increased expression of iNOS may play a critical role in the early pathophysiological events leading to IH-mediated neurobehavioral deficits.

Hypoxia alters cellular metabolism and although the effects of sustained hypoxia (SH) have been extensively studied, less is known about chronic intermittent hypoxia (IH), commonly associated with cardiovascular morbidity and stroke. We hypothesize that impaired glutamate homeostasis after chronic IH may underlie vulnerability to stroke-induced excitotoxicity. P16 organotypic hippocampal slices, cultured for 7 days were exposed for 7 days to IH (alternating 2 min 5% O2-15 min 21% O2), SH (5% O2) or RA (21% O2), then 3 glutamate challenges. The first and last exposures were intended as a metabolic stimulus (200 µM glutamate, 15 min); the second emulated excitotoxicity (10 mM glutamate, 10 min). GFAP, MAP2, and EAAT1, EAAT2 glutamate transporters expression were assessed after exposure to each hypoxic protocol. Additionally, cell viability was determined at baseline and after each glutamate challenge, in presence or absence of ceftriaxone that increases glutamate transporter expression. GFAP and MAP2 decreased after 7 days IH and SH. Long-term IH but not SH decreased EAAT1 and EAAT2. Excitotoxic glutamate challenge decreased cell viability and the following 200 µM exposure further increased cell death, particularly in IH-exposed slices. Ceftriaxone prevented glutamate transporter decrease and improved cell viability after IH and excitotoxicity. We conclude that IH is more detrimental to cell survival and glutamate homeostasis than SH. These findings suggest that impaired regulation of extracellular glutamate levels is implicated in the increased brain susceptibility to excitotoxic insult after long-term IH.

Adverse childhood experiences (ACEs) are linked to multiple adverse health outcomes. This study examined the association between ACEs and cancer diagnosis.Data from the 2010 Behavioral Risk Factor Surveillance System (BRFSS) survey were used. The BRFSS is the largest ongoing telephone health survey, conducted in all US states, the District of Columbia, Puerto Rico, Guam and the U.S. Virgin Islands, and provides data on a variety of health issues among the non-institutionalized adult population. Principal component analysis (PCA) was used to derive components for ACEs. Multivariable logistic regression models were used to provide adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between ACE components and overall, childhood and adulthood cancer, adjusting for confounders such as age, gender, race/ethnicity, income, educational status, marital status, and insurance status.Approximately 62% of respondents reported being exposed to ACEs and about one in ten respondents reported ever having been diagnosed with cancer. Component 1, which had the sexual abuse variables with the highest weights, was significantly associated with adulthood cancer (adjusted OR: 1.21; 95% CI: 1.03-1.43).The association between ACEs and adulthood cancer may be attributable to disease progression through association of ACEs with risk factors for other chronic diseases. More research should focus on the impact of sexual abuse ACEs and adverse health outcomes.

Sporadic inclusion-body myositis (s-IBM) is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer’s disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer’s disease.

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is a widely distributed single-stranded DNA parvovirus that has been responsible for major losses in wild and farmed penaeid shrimp populations on the northwestern Pacific coast of Mexico since the early 1990's. IHHNV has been considered a slow-evolving, stable virus because shrimp populations in this region have recovered to pre-epizootic levels, and limited nucleotide variation has been found in a small number of IHHNV isolates studied from this region. To gain insight into IHHNV evolutionary and population dynamics, we analyzed IHHNV capsid protein gene sequences from 89 Penaeus shrimp, along with 14 previously published sequences. Using Bayesian coalescent approaches, we calculated a mean rate of nucleotide substitution for IHHNV that was unexpectedly high (1.39x10(-4) substitutions/site/year) and comparable to that reported for RNA viruses. We found more genetic diversity than previously reported for IHHNV isolates and highly significant subdivision among the viral populations in Mexican waters. Past changes in effective number of infections that we infer from Bayesian skyline plots closely correspond to IHHNV epizootiological historical records. Given the high evolutionary rate and the observed regional isolation of IHHNV in shrimp populations in the Gulf of California, we suggest regular monitoring of wild and farmed shrimp and restriction of shrimp movement as preventative measures for future viral outbreaks.

Background and aimsAcute kidney injury (AKI) has a poor prognosis in cirrhosis. Given the variability of creatinine, the prediction of AKI and dialysis by other markers is needed. The aim of this study is to determine the role of serum and urine metabolomics in the prediction of AKI and dialysis in an inpatient cirrhosis cohort.Approach and resultsInpatients with cirrhosis from 11 North American Consortium of End-stage Liver Disease centers who provided admission serum/urine when they were AKI and dialysis-free were included. Analysis of covariance adjusted for demographics, infection, and cirrhosis severity was performed to identify metabolites that differed among patients (1) who developed AKI or not; (2) required dialysis or not; and/pr (3) within AKI subgroups who needed dialysis or not. We performed random forest and AUC analyses to identify specific metabolite(s) associated with outcomes. Logistic regression with clinical variables with/without metabolites was performed. A total of 602 patients gave serum (218 developed AKI, 80 needed dialysis) and 435 gave urine (164 developed AKI, 61 needed dialysis). For AKI prediction, clinical factor-adjusted AUC was 0.91 for serum and 0.88 for urine. Major metabolites such as uremic toxins (2,3-dihydroxy-5-methylthio-4-pentenoic acid [DMTPA], N2N2dimethylguanosine, uridine/pseudouridine) and tryptophan/tyrosine metabolites (kynunerate, 8-methoxykyunerate, quinolinate) were higher in patients who developed AKI. For dialysis prediction, clinical factor-adjusted AUC was 0.93 for serum and 0.91 for urine. Similar metabolites as AKI were altered here. For dialysis prediction in those with AKI, the AUC was 0.81 and 0.79 for serum/urine. Lower branched-chain amino-acid (BCAA) metabolites but higher cysteine, tryptophan, glutamate, and DMTPA were seen in patients with AKI needing dialysis. Serum/urine metabolites were additive to clinical variables for all outcomes.ConclusionsSpecific admission urinary and serum metabolites were significantly additive to clinical variables to predict AKI development and dialysis initiation in inpatients with cirrhosis. These observations can potentially facilitate earlier initiation of renoprotective measures.

Gender differences in the natural history of chronic liver disease have been well-described. Women have lower rates of chronic liver disease and slower fibrosis progression, yet higher rates of waitlist mortality.1,2 Although previous studies have identified several clinical factors including height and creatinine that explain some of this transplant disparity, most have used data from administrative records, which are limited in their ability to identify clinically relevant differences and opportunities for intervention to reduce disparities.3-5 Additionally, most studies have focused on the period between waitlist and transplant, failing to capture gender differences in access to transplant.3,6 In the present study, we took advantage of a multicenter inpatient cohort with granular clinical data to characterize how women and men with cirrhosis differ, to stimulate future research aimed at reducing the well-established gender disparity in liver transplantation.

Background & aimsInpatients with cirrhosis have high rates of acute-on-chronic failure (ACLF) development and high mortality within 30 days of admission to the hospital. Better biomarkers are needed to predict these outcomes. We performed metabolomic analyses of serum samples from patients with cirrhosis at multiple centers to determine whether metabolite profiles might identify patients at high risk for ACLF and death.MethodsWe performed metabolomic analyses, using liquid chromatography, of serum samples collected at time of admission to 12 North American tertiary hepatology centers from 602 patients in the North American Consortium for the Study of End-Stage Liver Disease sites from 2015 through 2017 (mean age, 56 years; 61% men; mean model for end-stage liver disease score, 19.5). We performed analysis of covariance, adjusted for model for end-stage liver disease at time of hospital admission, serum levels of albumin and sodium, and white blood cell count, to identify metabolites that differed between patients who did vs did not develop ACLF and patients who did vs did not die during hospitalization and within 30 days. We performed random forest analysis to identify specific metabolite(s) that were associated with outcomes and area under the curve (AUC) analyses to analyze them in context of clinical parameters. We analyzed microbiomes of stool samples collected from 133 patients collected at the same time and examined associations with serum metabolites.ResultsOf the 602 patients analyzed, 88 developed ACLF (15%), 43 died in the hospital (7%), and 72 died within 30 days (12%). Increased levels of compounds of microbial origin (aromatic compounds, secondary or sulfated bile acids, and benzoate) and estrogen metabolites, as well as decreased levels of phospholipids, were associated with development of ACLF, inpatient, and 30-day mortality and were also associated with fecal microbiomes. Random forest analysis and logistic regression showed that levels of specific microbially produced metabolites identified patients who developed ACLF with an AUC of 0.84 (95% confidence interval [CI] 0.78-0.88; P = .001), patients who died while in the hospital with an AUC of 0.81 (95% CI 0.74-0.85; P = .002), and patients who died within 30 days with an AUC of 0.77 (95% CI 0.73-0.81; P = .02). The metabolites were significantly additive to clinical parameters for predicting these outcomes. Metabolites associated with outcomes were also correlated with microbiomes of stool samples.ConclusionsIn an analysis of serum metabolites and fecal microbiomes of patients hospitalized with cirrhosis at multiple centers, we associated metabolites of microbial origin and lipid moieties with development of ACLF and death as an inpatient or within 30 days, after controlling for clinical features.

To guarantee equal opportunities and treatment in employment for individuals with disabilities, Congress enacted Title I of the Americans with Disabilities Act (ADA) in 1992. This law states, "No covered entity shall discriminate against a qualified individual on the basis of disability in regard to job application procedures, the hiring, advancement, or discharge of employees, employee compensation, job training, and other terms, conditions, and privileges of employment" (Americans with Disabilities Act of 1990). However, disability advocates expressed concern that Americans with disabilities appeared to be less protected in the workplace than was expected under Title I of the ADA. This raised concerns in Congress that the original intent of the ADA was not being upheld. To restore the intended purposes and protections of the ADA, Congress proposed the ADA Amendments Act of 2008 (ADAAA) which was designed to have less emphasis on the evaluation of whether an individual was qualified for coverage and more emphasis on whether or not an employer had unlawfully discriminated against that individual (Vierling, 2009). The purpose of this study was to identify where to focus resources regarding specific aspects of employment based on perceived discrimination and outcome resolutions from individuals with visual impairments. The following research questions guided this study: (1) Are there differences between discrimination charges filed with the U.S. Equal Employment Opportunity Commission (EEOC) before and after the enactment of the ADAAA regarding a visual impairment? and (2) Are there differences between outcome resolutions before and after the enactment of the ADAAA regarding a visual impairment?

ObjectivesNosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis.MethodsNorth American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality.ResultsThe study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death.DiscussionNIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.

BackgroundHepatic encephalopathy (HE) can adversely affect outcomes in both in-patients and out-patients with cirrhosis.AimTo define targets for improving quality of care in HE management in the multi-centre North American Consortium for End-Stage Liver Disease (NACSELD) cohort.MethodNACSELD in-patient cohort was analysed for (a) medication-associated precipitants, (b) aspiration pneumonia development, (c) HE medication changes, and (d) 90-day HE recurrence/readmissions. Comparisons were made between patients on no-therapy, lactulose only, rifaximin only or both. Ninety-day HE-readmission analysis was adjusted for MELD score.ResultsTwo thousand eight hundred and ten patients (1102 no-therapy, 659 lactulose, 154 rifaximin, 859 both) were included. HE on admission, and HE rates during hospitalisation were highest in those on lactulose only or dual therapy compared to no-therapy or rifaximin only (P

ObjectivesAntibiotic prophylaxis is recommended for prevention of the first episode of spontaneous bacterial peritonitis (SBP; primary prophylaxis 1°) and subsequent episodes (secondary prophylaxis 2°). We aimed to compare outcomes in cirrhotic inpatients on 1° vs 2° SBP prophylaxis.MethodsData from North American Consortium for the Study of End-Stage Liver Disease were evaluated for cirrhosis details, reasons for admission/medications, inpatient course recorded, and outcomes over 90 days. Outcomes (intensive care units, acute kidney injury, inpatient/90-day mortality) were compared between the 2 groups after propensity-matching on admission model for end-stage liver disease (MELD) score and serum albumin.ResultsAmong the 2,731 patients enrolled, 305 were on 1° and 187 on 2° SBP prophylaxis. After propensity-matching, 154 patients remained in each group. Patients on 1° prophylaxis were more likely to have admission systemic inflammatory response syndrome (P = 0.02), with higher intensive care unit admissions (31% vs 21%; P = 0.05) and inpatient mortality (19% vs 9%; P = 0.01) than the 2° prophylaxis group. Patients on 2° prophylaxis had higher total (22% vs 10%; P = 0004), readmission (16% vs 9%; P = 0.03), and nosocomial (6% vs 0.5%; P = 0.01) SBP rates with predominant Gram-negative organisms compared to 1° prophylaxis patients. At 90 days, 1° prophylaxis patients had a higher mortality (35% vs 22%; P = 0.02) and acute kidney injury incidence (48% vs 30%; P = 0.04) compared to 2° prophylaxis patients.DiscussionIn this inpatient cirrhosis study, despite prophylaxis, a high proportion of patients developed SBP, which was associated with mortality. Cirrhotic inpatients on 1° prophylaxis had worse outcomes than those on 2° prophylaxis when propensity-matched for the MELD score and serum albumin during the index admission and 90-day follow-up.

BackgroundCirrhosis can alter several metabolic pathways. Metabolomics could prognosticate outcomes like hepatic encephalopathy (HE), transplant, hospitalization and death.AimDetermine changes in serum and urine metabolomics in cirrhotics who develop outcomes.MethodsCirrhotic outpatients underwent data, serum/urine collection and were followed for 90 days. Demographics, cirrhosis details and medications were collected. Metabolomics was performed on urine/serum using GC/MS with subsequent bioinformatics analyses (ChemRICH, MetaMAPP and PLS-DA). Logistic regression adjusting for covariates (demographics, alcohol etiology, prior HE, PPI, SBP prophylaxis, rifaximin/lactulose) were performed and ROC curves comparing MELD to adjusted serum & urine metabolites were created.Results211 patients gave serum, of which 64 were hospitalized, 19 developed HE, 13 were transplanted and 11 died. 164 patients gave urine of which 56 were hospitalized, 18 developed HE, 12 were transplanted and 11 died. Metabolomics: Saturated fatty acids, amino acids and bioenergetics-related metabolites differentiated patients with/without outcomes. After regression, 232, 228, 284 and 229 serum metabolites were significant for hospitalization, HE, death and transplant. In urine 290, 284, 227 & 285 metabolites were significant for hospitalization, HE, death and transplant respectively. AUC was higher for serum metabolites vs MELD for HE (0.85 vs.0.76), death (0.99 vs.0.88), transplant (0.975 vs.0.94) and hospitalizations (0.84 vs.0.83). Similarly, urinary metabolite AUC was also higher than MELD for HE (0.87 vs.0.72), death (0.92 vs 0.86), transplant (0.99 vs.0.90) and hospitalizations (0.89 vs.0.84).ConclusionsIn this exploratory study, serum and metabolites focused on lipid, bioenergetics and amino acid metabolism are altered in cirrhotics who develop negative outcomes.

Objective This study tested a randomized controlled trial of RVA Breathes, a community asthma program, in reducing asthma-related healthcare utilization among children living in an area with a high poverty rate. Methods Participants included 250 caregivers (78% African American/Black; 73.3% household income<$25,000/year) and their children with asthma (5–11 years). Inclusion criteria included an asthma-related emergency department (ED) visit, hospitalization, unscheduled doctor's visit, or systemic steroids in the past 2 years. Families were randomized to a full active intervention (asthma education with community health workers [CHWs], home remediation with home assessors, and a school nurse component; n  = 118), partial active intervention (asthma education and home remediation; n  = 69), or a control group (n  = 63) for 9 months. Measures on healthcare utilization and asthma-related factors were collected. Follow-up assessments occurred across a 9-month period. Results Although we did not find any significant effects, there was a trend toward significance for a group by time effect with objective healthcare utilization as the outcome (F 4,365   =   2.28, p  =  .061). The full intervention group experienced a significant decrease from baseline to 9-month follow-up compared with the other groups (p  <  .001). Only the full intervention group experienced a significant increase in reported asthma action plans across time (no significant group effect). Conclusions In the context of the unprecedented COVID-19 pandemic, which led to a substantial global decrease in healthcare utilization, the study's main hypotheses were not supported. Nevertheless, findings support the benefit of community asthma programs that integrate care across multiple settings and connect families with CHWs. [ABSTRACT FROM AUTHOR]