Evaluating quality of life tools in North American patients with erythropoietic protoporphyria and X-linked protoporphyria.

BackgroundErythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare photodermatoses presenting with severe phototoxicity. Although anecdotally, providers who treat EPP patients acknowledge their life-altering effects, tools that fully capture their impact on quality of life (QoL) are lacking.MethodsAdult patients with EPP/XLP were given four validated QoL tools: the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), the Hospital Anxiety and Depression Scale (HADS), the Illness Perception Questionnaire Revised (IPQR), and an EPP-Specific tool. All patients received the PROMIS-57 while the HADS, IPQR, and EPP-Specific tools were introduced at a later date. Associations between responses and clinical phenotypes were explored.ResultsTwo hundred and two patients were included; 193 completed PROMIS-57, 104 completed IPQR, 103 completed HADS, and 107 completed the EPP-Specific tool. The IPQR showed that patients strongly believed EPP/XLP had a negative impact on their lives. Mean scores in anxiety and depression domains of both HADS and PROMIS-57 were normal; however, anxiety scores from HADS were borderline/abnormal in 20% of patients. The EPP-Specific tool revealed a decreased QoL in most patients. The PROMIS-57 showed that 21.8% of patients have clinically significant pain interference. Several tool domains correlated with measures of disease severity, most being from the PROMIS-57.ConclusionsImpaired QoL is an important consequence of EPP/XLP. PROMIS-57 was most sensitive in evaluating impaired QoL in EPP/XLP. Further research is needed to compare the effectiveness of it for assessing response to treatment

Laboratory Evaluations of Stabilized Flue Gas Desulfurization Sludge (Scrubber Sludge) and Aggregate Mixtures

The Kentucky Transportation Research Program has completed a laboratory study involving the use of flue gas desulfurization sludge (scrubber sludge) for potential application as a highway subbase and/or embankment material. Scrubber sludge is a waste produet formed when fly ash (and other residue) is combined with a lime dust slurry filter cake and stabilized with quicklime (calcium oxide). Samples of stockpiled (field) sludge and dry sludge components were obtained from the Robert Reid Station (Big Rivers Electric Corporation) in Sebree, Kentuclty. Dry sludge components (fly ash, filter cake, and quicklime) were uaed to prepare sludge samples in the laboratory, allowing a higher degree of quality control for compariaon purposes. Mixtures for testing included scrubber sludge, scrubber sludge with pond ash (bottom ash), and scrubber sludge with dense graded limestone aggregate (DGA). One objective of laboratory analyses was the determination of optimum mixture proportions. A mixture of 20-percent scrubber sludge and 80-percent pond ash was determined to be the optimum design mix. That mixture showed significant strength gain with curing and had a static-chord modulus of elasticity approximately 118 times the compressive strength. Strength and modulus tests indicated that mixtures of scrubber sludge and pond ash were superior to mixtures of scrubber sludge and DGA. The scope of the study, however, did not permit complete explanation of these observations. An economic study showed that scrubber sludge with pond ash can be used economically as a highway subbase material, especially on low-fatigue roads, by partially replacing more expensive pavement layers. Triaxial tests and computer simulations indicated that scrubber sludge could be used as an embankment material in some applications. However, this would be economical only if suitable fill material was not available at or near the fill site

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of non-communicable diseases in adulthood, potentially mediated by chronic low-grade inflammation. Glycoprotein acetyls (GlycA) is a marker of chronic and cumulative inflammation. We investigated associations between ACEs and GlycA at different ages, in two generations of the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS: ALSPAC offspring's total ACE scores were generated for two age periods using prospectively collected data: 0-7y and 0-17y. GlycA was measured using high-resolution proton nuclear magnetic resonance at mean ages 8y, 18y, and 24y. Sample sizes ranged from: n = 5116 (8y) to n = 3085 (24y). ALSPAC mothers (n = 4634) retrospectively reported ACEs experienced before age 18y and GlycA was assessed at mean age 49y. We used multivariable linear regression to estimate associations between ACEs (total ACE score and individual ACEs) and subsequent GlycA in both samples, adjusting for key confounders. RESULTS: Mean GlycA levels were similar in offspring and mothers and over time. In offspring, there was no evidence that ACEs (total score or individual ACE) were associated with GlycA at age 8y or 18y, or 24y after adjustment for maternal age at birth and parity, maternal marital status, household occupational social class, maternal education, maternal smoking, own ethnicity, sex, and age in months. In mothers, there was evidence of a positive association between the total ACE score and GlycA at age 49y (adjusted mean difference 0.007 mmol/L; 95%CI: 0.003, 0.01). Emotional neglect was the only individual ACE associated with higher GlycA after adjusting for confounders and other ACEs. CONCLUSION: Results suggest the association between ACEs and GlycA may emerge in middle age. Future research should explore the extent to which inflammation in adulthood mediates well-documented associations between ACEs and adverse health outcomes in later life

The 1+1-dimensional Kardar-Parisi-Zhang equation and its universality class

We explain the exact solution of the 1+1 dimensional Kardar-Parisi-Zhang equation with sharp wedge initial conditions. Thereby it is confirmed that the continuum model belongs to the KPZ universality class, not only as regards to scaling exponents but also as regards to the full probability distribution of the height in the long time limit.Comment: Proceedings StatPhys 2

Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of non-communicable diseases in adulthood, potentially mediated by chronic low-grade inflammation. Glycoprotein acetyls (GlycA) is a marker of chronic and cumulative inflammation. We investigated associations between ACEs and GlycA at different ages, in two generations of the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS: ALSPAC offspring’s total ACE scores were generated for two age periods using prospectively collected data: 0-7y and 0-17y. GlycA was measured using high-resolution proton nuclear magnetic resonance at mean ages 8y, 18y, and 24y. Sample sizes ranged from: n = 5116 (8y) to n = 3085 (24y). ALSPAC mothers (n = 4634) retrospectively reported ACEs experienced before age 18y and GlycA was assessed at mean age 49y. We used multivariable linear regression to estimate associations between ACEs (total ACE score and individual ACEs) and subsequent GlycA in both samples, adjusting for key confounders. RESULTS: Mean GlycA levels were similar in offspring and mothers and over time. In offspring, there was no evidence that ACEs (total score or individual ACE) were associated with GlycA at age 8y or 18y, or 24y after adjustment for maternal age at birth and parity, maternal marital status, household occupational social class, maternal education, maternal smoking, own ethnicity, sex, and age in months. In mothers, there was evidence of a positive association between the total ACE score and GlycA at age 49y (adjusted mean difference 0.007 mmol/L; 95%CI: 0.003, 0.01). Emotional neglect was the only individual ACE associated with higher GlycA after adjusting for confounders and other ACEs. CONCLUSION: Results suggest the association between ACEs and GlycA may emerge in middle age. Future research should explore the extent to which inflammation in adulthood mediates well-documented associations between ACEs and adverse health outcomes in later life

Profiles of miRNAs in serum in severe acute drug induced liver injury and their prognostic significance

Background & AimsDrug induced liver injury (DILI) is challenging because of the lack of biomarkers to predict mortality. Our aim was to describe miRNA changes in sera of subjects with acute idiosyncratic DILI and determine if levels of miRNAs were associated with 6 month mortality.MethodsClinical data and sera were collected from subjects enrolled in the Drug Induced Liver Injury Network prospective study. miRNAs were isolated from serum obtained from 78 subjects within 2 weeks of acute DILI and followed up for 6 months or longer. miRNAs were compared to 40 normal controls and 6 month survivors vs non‐survivors.ResultsThe mean age of the DILI cohort was 48 years, and 55% were female. Eleven (14.1%) subjects died, 10 within 6 months of DILI onset, 5 (45%) liver related. Lower levels of miRNAs‐122, ‐4463 and ‐4270 were associated with death within 6 months (P<.05). None of the subjects with miRNA‐122 greater than the median value died within 6 months for a sensitivity of 100% and specificity of 57%. In subjects with a serum albumin <2.8 g/dL and miR‐122<7.89 RFU the sensitivity, specificity, positive and negative predictive values for death within 6 months were 100%, 57%, 38% and 100% respectively.ConclusionsSerum miRNA‐122 combined with albumin accurately identified subjects who died within 6 months of drug induced liver injury. If confirmed prospectively, miRNA‐122 and albumin may be useful in identifying patients at high risk for mortality or liver transplantation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136681/1/liv13312_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136681/2/liv13312.pd

Report of the Coding Committee of the Association for European Paediatric Cardiology

IN 1999 AND EARLY 2000, THE ASSOCIATION FOR European Paediatric Cardiology published the European Paediatric Cardiac Code as independent but linked Short and Long Lists, containing 650 and 3876 primary terms respectively. The historical background and rationale for development of this coding system has been previously detailed, but essentially it followed a series of meeting of the coding committee of the Association between 1997-1999, during which a pre-existing Long List was adopted and then used to create the condensed Short List. The system was published as the recommended standard coding system for use across Europe, covering the diagnosis and therapy of children with congenital and acquired cardiac disease. The scope of the lists was to encompass the needs of all those involved with such patients, from the fetal cardiologist through to the specialist in adult congenital heart disease; and from the general paediatric cardiologist and cardiac surgeon, to those specialising in transcatheter interventions, paediatric electrophysiology, and paediatric echocardiographers. In addition, the code was crossmapped to the 9th and 10th revisions of the International Classification of Diseases ("ICD-9” and "ICD-10”) provided by the World Health Organisation in order to facilitate returns to central government, a requirement in most countries. In so doing, it was hoped to address the concerns of many centres that such information submitted by professional coding staff was often inaccurate due to the complex nature of congenital cardiac disease, together with the limited scope and vague terminology of the International listing

Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases

The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 +/- 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 +/- 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 +/- 6 percent, T4+4B4+: 23.0 +/- 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 +/- 3 percent, T4+4B4+: 33.1 +/- 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 +/- 7 percent) and gout (14.3 +/- 7 percent) was decreased compared with that of normal controls (19.0 +/- 6 percent) (osteoarthritis versus normal controls p &lt;0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity. The results indicate that diminished proportions of CD4+2H4+ (suppressor-inducer) cells and increased proportions of CD4+4B4+ (helper) cells are a common feature of CD4+ cells in synovial fluid in rheumatoid arthritis as well as a variety of other inflammatory disorders, whereas modest changes in CD4+2H4+ peripheral blood lymphocytes are seen in older individuals and more marked decreases are observed only in a more selected group of patients. These changes may be of potential functional importance in the regulation of the immune response in a variety of clinical settings.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27324/1/0000347.pd