Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Hemophilic siblings provide a unique population to explore the natural history of chronic hepatitis C

Identifying barriers to evidence-based care for sickle cell disease: Results from the Sickle Cell Disease Implementation Consortium cross-sectional survey of healthcare providers in the USA

OBJECTIVES: Sickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD. METHODS: The SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers\u27 perspective. RESULTS: Respondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients\u27 medical needs were addressed while only 22% felt their mental health needs were met. CONCLUSIONS: A substantial number of providers did not know about NHLBI\u27s SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers\u27 specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model.

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. RESULTS: Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02-1.10, 95% CI range [1.004-1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58-3.28 95% CI range [1.18-4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46-0.64, 95% CI range [0.34-0.86]). CONCLUSIONS: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes

Examining mental health, education, employment, and pain in sickle cell disease

IMPORTANCE: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain. OBJECTIVE: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022. MAIN OUTCOMES AND MEASURES: Electronic medical record abstraction and a participant survey provided demographic data, mental health diagnosis, and Adult Sickle Cell Quality of Life Measurement Information System pain scores. Multivariable regression was used to examine the associations of education, employment, and mental health with the main outcomes (pain frequency and pain severity). RESULTS: The study enrolled a total of 2264 participants aged 15 to 45 years (mean [SD] age, 27.9 [7.9] years; 1272 female participants [56.2%]) with SCD. Nearly one-half of the participant sample reported taking daily pain medication (1057 participants [47.0%]) and/or hydroxyurea use (1091 participants [49.2%]), 627 participants (28.0%) received regular blood transfusion, 457 (20.0%) had a depression diagnosis confirmed by medical record abstraction, 1789 (79.8%) reported severe pain (rated most recent pain crises as ≥7 out of 10), and 1078 (47.8%) reported more than 4 pain episodes in the prior 12 months. The mean (SD) pain frequency and severity t scores for the sample were 48.6 (11.4) and 50.3 (10.1), respectively. Educational attainment and income were not associated with increased pain frequency or severity. Unemployment (β, 2.13; 95% CI, 0.99 to 3.23; P \u3c .001) and female sex (β, 1.78; 95% CI, 0.80 to 2.76; P \u3c .001) were associated with increased pain frequency. Age younger than 18 years was inversely associated with pain frequency (β, -5.72; 95% CI, -7.72 to -3.72; P \u3c .001) and pain severity (β, 5.10; 95% CI, -6.70 to -3.51; P \u3c .001). Depression was associated with increased pain frequency (β, 2.18; 95% CI, 1.04 to 3.31; P \u3c .001) but not pain severity. Hydroxyurea use was associated with increased pain severity (β, 1.36; 95% CI, 0.47 to 2.24; P = .003), and daily use of pain medication was associated with both increased pain frequency (β, 6.29; 95% CI, 5.28 to 7.31; P \u3c .001) and pain severity (β, 2.87; 95% CI, 1.95 to 3.80; P \u3c .001). CONCLUSIONS AND RELEVANCE: These findings suggest that employment status, sex, age, and depression are associated with pain frequency among patients with SCD. Depression screening for these patients is warranted, especially among those experiencing higher pain frequency and severity. Comprehensive treatment and pain reduction must consider the full experiences of patients with SCD, including impacts on mental health

Patient Reported Outcomes in Sickle Cell Disease Examined Within a Conceptual Model

Objective: To examine the relations between patient reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD related factors and barriers to care would independently contribute to functioning as measured using the PRO domains. Additionally, pain and other SCD related complications are expected to impact the relation between the variables. Methods: Participants completed a 48-item survey that included socio-demographics and PRO measures, such as social functioning, pain impact emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency, timing and severity, and barriers to medical care. Healthcare utilization was obtained from medical records abstractions. Results: Higher pain frequency and severity and history of treatment for depression were associated with higher odds of worse outcomes in almost all PRO domains, controlling for age and gender for the 2,054 participants. Such social determinants of health as lower household income and unemployment, particularly due to disability status, were associated with higher odds of worse outcomes. Reports of fewer individual barriers to care were associated with better outcomes in emotion, social, cognitive and fatigue domains, while reports of fewer self-reported SCD complications/treatments were associated with better outcomes in emotion and sleep impact domains. Conclusions: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes. @font-face {font-family: Cambria Math ; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face {font-family:Times; panose-1:2 0 5 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1342185562 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent: ; margin:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family: Times New Roman ,serif; mso-fareast-font-family: Times New Roman ;}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-family: Calibri ,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family: Times New Roman ; mso-bidi-theme-font:minor-bidi;}div.WordSection1 {page:WordSection1;

Bicuspid and unicuspid aortic valves: Different phenotypes of the same disease? Insight from the GenTAC Registry

BackgroundUnicuspid aortic valve (UAV) is a rare disorder, often difficult to distinguish from bicuspid aortic valve (BAV). BAV and UAV share valve pathology such as the presence of a raphe, leaflet fusion, aortic stenosis, aortic regurgitation, and/or ascending aortic dilatation, but a comprehensive echocardiographic comparison of patients with UAV and BAV has not been previously performed.MethodsWe investigated UAV and BAV patients at an early stage of disease included in GenTAC, a national registry of genetically related aortic aneurysms and associated cardiac conditions. Clinical and echocardiographic data from the GenTAC Registry were compared between 17 patients with UAV and 17 matched‐controls with BAV.ResultsBaseline characteristics including demographics, clinical findings including family history of BAV and aortic aneurysm/coarctation, and echocardiographic variables were similar between BAV and UAV patients; aortic stenosis was more common and more severe in patients with UAV. This was evidenced by higher mean and peak gradient, smaller aortic valve area, and more advanced valvular degeneration (all P < .05). There were no significant differences in aortic dimensions, with a similar pattern of enlargement of the ascending aorta.ConclusionsThe similar baseline characteristics with more accelerated aortic valve degeneration and stenosis suggest that UAV represents an extreme in the spectrum of BAV syndromes. Therefore, it is reasonable to consider application of recommendations for the management of patients with BAV to those with the rarer UAV.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139976/1/chd12520.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139976/2/chd12520_am.pd

HLA-B*35-Px–mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses

A subset of HLA-B*35 alleles, B*35-Px, are strongly associated with accelerated HIV-1 disease progression for reasons that are not understood. Interestingly, the alternative set of B*35 subtypes, B*35-PY, have no detectable impact on HIV-1 disease outcomes, even though they can present identical HIV-1 epitopes as B*35-Px molecules. Thus, the differential impact of these alleles on HIV-1 disease progression may be unrelated to interactions with HIV-1–specific CD8+ T cells. Here, we show that the B*35-Px molecule B*3503 binds with greater affinity to immunoglobulin-like transcript 4 (ILT4), an inhibitory MHC class I receptor expressed on dendritic cells, than does the B*35-PY molecule B*3501, even though these two B*35 molecules differ by only one amino acid and present identical HIV-1 epitopes. The preferential recognition of B*3503 by ILT4 was associated with significantly stronger dendritic cell dysfunction in in vitro functional assays. Moreover, HIV-1–infected carriers of B*3503 had poor dendritic cell functional properties in ex vivo assessments when compared with carriers of the B*3501 allele. Differential interactions between HLA class I allele subtypes and immunoregulatory MHC class I receptors on dendritic cells thus provide a novel perspective for the understanding of MHC class I associations with HIV-1 disease progression and for the manipulation of host immunity against HIV-1

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogeni

Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

<p>Abstract</p> <p>Background</p> <p>Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS).</p> <p>Methods</p> <p>In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV) seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with <it>P</it>_trend≤ 0.15 were retained in a backward elimination regression model.</p> <p>Results</p> <p>Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (OR_adj) 0.96, 95% confidence interval (CI) 0.73 - 1.25, <it>P</it>_trend= 0.87], nor was it related to any factor scores or cluster of plants (<it>P </it>= 0.11 to 0.81). In the elimination regression model, KS risk was associated with five plants (<it>P</it>_trend= 0.02 to 0.10) and with residential exposure to six soils (<it>P</it>_trend= 0.01 to 0.13), including three soils (eutric regosol, chromic/pellic vertisol) used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (OR_adj4.69, 95% CI 1.97 - 11.17), but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (OR_adj7.47, 95% CI 3.04 - 18.35) and lower for current and former smokers (OR_adj0.26 and 0.47, respectively, <it>P</it>_trend= 0.05).</p> <p>Conclusions</p> <p>KS risk was associated with exposure to a few plants and soils, but these may merely be due to chance. Study of the effects of durum wheat, which was previously associated with cKS, may be warranted.</p

Circulating interleukin-6 (IL-6) levels are associated with aortic dimensions in genetic aortic conditions.

BACKGROUND:Biomarkers that reflect progression of dilatation of the aorta in patients with aortic conditions are needed as surrogate tools to assist in monitoring the condition in a non-invasive manner in combination with imaging procedures. This study aimed to investigate whether biomarkers are associated with aortic dimensions in patients enrolled in the Genetically-Triggered Thoracic Aortic Conditions (GenTAC) registry. METHODS:Plasma samples of 159 patients enrolled in the GenTAC registry were assessed for circulating biomarkers [interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2) and transforming growth factor-β1 (TGFβ1)]. Association of circulating biomarker levels with aortic dimensions was investigated. RESULTS:IL-6 showed significant positive correlations with aortic dimensions at each segment of the aorta, with the correlation increasing in more distal aortic regions (ascending aorta, R = 0.26, p = 0.004; proximal arch, R = 0.35, p<0.0001; transverse arch, R = 0.30, p = 0.0005; mid-descending thoracic aorta, R = 0.40, p<0.0001; thoracoabdominal aorta, R = 0.38, p<0.0001; suprarenal abdominal aorta, R = 0.42, p<0.0001; and infrarenal aorta, R = 0.43, p<0.0001). TIMP-1 showed a significant correlation albeit weaker than IL-6, and also showed increasing correlation towards the distal areas of the aorta. CONCLUSIONS:Circulating IL-6 and TIMP-1 were associated with aortic dimensions in patients with aortopathies enrolled in the GenTAC cohort