A CLINICAL AND SEROLOGIC COMPARISON OF AFRICAN-AMERICAN AND CAUCASIAN PATIENTS WITH SYSTEMIC SCLEROSIS

PubMed Central

Steen, Virginia; Domsic, Robyn T.; Lucas, Mary; Fertig, Noreen; Medsger, Thomas A.

2013-01-01

Objective Epidemiology studies suggest that Systemic Sclerosis is more common, occurs at a younger age and is more severe in African-Americans than Caucasians. However, the scleroderma autoantibody profile is very different between these two ethnic subgroups. This study examines the demographic and disease features, frequency and severity of internal organ system involvement and survival in African-American and Caucasian SSc patients with particular attention to their serum autoantibody profiles. Methods Demographic, clinical, autoantibody, natural history of organ involvement and survival were studied in consecutive African-American and Caucasian patients seen between 1972 and 2007 as part of the Pittsburgh Scleroderma Database. The Medsger Disease Severity Scale was used to determine severe disease. Results African-American patients were more likely to have anti topoisomerase, anti U1RNP and U3 RNP auto-antibodies. Comparing African-American and Caucasians with these antibodies, African-American patients with anti topoisomerase antibody had more frequent and more severe pulmonary fibrosis than Caucasians and an associated decreased survival. Pulmonary fibrosis was also more severe in the U1 RNP patients but was not associated with a difference in survival between African Americans and Caucasians. Anti U3 RNP was associated with more severe gastrointestinal involvement in African-American’s compared to Caucasians. Conclusions African Americans with systemic sclerosis have more severe disease complications than Caucasians both because of the type of autoantibody they have and because they have more severe interstitial lung disease even within the antibody subset. Early aggressive intervention in all African Americans with interstitial lung disease should be a priority. PMID:22576620

White-Nose Syndrome Disease Severity and a Comparison of Diagnostic Methods.

PubMed

McGuire, Liam P; Turner, James M; Warnecke, Lisa; McGregor, Glenna; Bollinger, Trent K; Misra, Vikram; Foster, Jeffrey T; Frick, Winifred F; Kilpatrick, A Marm; Willis, Craig K R

2016-03-01

White-nose syndrome is caused by the fungus Pseudogymnoascus destructans and has killed millions of hibernating bats in North America but the pathophysiology of the disease remains poorly understood. Our objectives were to (1) assess non-destructive diagnostic methods for P. destructans infection compared to histopathology, the current gold-standard, and (2) to evaluate potential metrics of disease severity. We used data from three captive inoculation experiments involving 181 little brown bats (Myotis lucifugus) to compare histopathology, quantitative PCR (qPCR), and ultraviolet fluorescence as diagnostic methods of P. destructans infection. To assess disease severity, we considered two histology metrics (wing area with fungal hyphae, area of dermal necrosis), P. destructans fungal load (qPCR), ultraviolet fluorescence, and blood chemistry (hematocrit, sodium, glucose, pCO2, and bicarbonate). Quantitative PCR was most effective for early detection of P. destructans, while all three methods were comparable in severe infections. Correlations among hyphae and necrosis scores, qPCR, ultraviolet fluorescence, blood chemistry, and hibernation duration indicate a multi-stage pattern of disease. Disruptions of homeostasis occurred rapidly in late hibernation. Our results provide valuable information about the use of non-destructive techniques for monitoring, and provide novel insight into the pathophysiology of white-nose syndrome, with implications for developing and implementing potential mitigation strategies.

Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures?

PubMed

Deutsch, Mariel B; Liang, Li-Jung; Jimenez, Elvira E; Mather, Michelle J; Mendez, Mario F

2016-09-01

Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE). We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD. Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales. We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity.

Are we comparing frontotemporal dementia and Alzheimer disease patients with the right measures?

PubMed Central

Deutsch, Mariel B.; Liang, Li-Jung; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.

2016-01-01

Background Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE). Methods We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD. Results Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales. Conclusion We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity. PMID:27079571

Plasma RANTES and eotaxin levels are correlated with the severity of chronic rhinosinusitis.

PubMed

Chao, Pin-Zhir; Chou, Chi-Ming; Chen, Chen-Ho

2012-11-01

Eosinophilia occurs in up to 75-90% of nasal polyps in Caucasians. The chemokines eotaxin and RANTES increase eosinophil recruitment, activation, and survival, and these chemokines are significantly expressed in nasal polyps. We hypothesized that eotaxin and RANTES plasma levels might be correlated with disease severity. We compared the eotaxin and RANTES plasma levels in 20 Taiwanese patients with chronic rhinosinusitis and nasal polyps and 20 Taiwanese healthy controls. Eotaxin and RANTES plasma levels were measured by ELISA and disease severity was scored by CT scans. Compared to controls, patients with nasal polyps had significantly elevated plasma levels of eotaxin and RANTES and increased peripheral blood eosinophils (p < 0.001). Eotaxin plasma levels were significantly correlated with disease severity in patients with chronic rhinosinusitis to a greater extent than were RANTES levels. RANTES and eotaxin levels were also positively correlated with the percentages of peripheral blood eosinophils. Eotaxin plasma levels are significantly correlated with disease severity in Taiwanese patients with nasal polyposis to a greater degree than are RANTES levels. Additional studies are needed to assess whether eotaxin plasma levels can be used to monitor disease progression and attenuation.

Coral diversity and the severity of disease outbreaks: a cross-regional comparison of Acropora white syndrome in a species-rich region (American Samoa) with a species-poor region (Northwestern Hawaiian Islands).

USGS Publications Warehouse

Aeby, G.S.; Bourne, D.G.; Wilson, B.; Work, Thierry M.

2011-01-01

The dynamics of the coral disease, Acropora white syndrome (AWS), was directly compared on reefs in the species-poor region of the Northwestern Hawaiian Islands (NWHI) and the species-rich region of American Samoa (AS) with results suggesting that biodiversity, which can affect the abundance of susceptible hosts, is important in influencing the impacts of coral disease outbreaks. The diversity-disease hypothesis predicts that decreased host species diversity should result in increased disease severity of specialist pathogens. We found that AWS was more prevalent and had a higher incidence within the NWHI as compared to AS. Individual Acropora colonies affected by AWS showed high mortality in both regions, but case fatality rate and disease severity was higher in the NWHI. The site within the NWHI had a monospecific stand of A. cytherea; a species that is highly susceptible to AWS. Once AWS entered the site, it spread easily amongst the abundant susceptible hosts. The site within AS contained numerous Acropora species, which differed in their apparent susceptibility to infection and disease severity, which in turn reduced disease spread. Manipulative studies showed AWS was transmissible through direct contact in three Acropora species. These results will help managers predict and respond to disease outbreaks.

Periodontal profile class is associated with prevalent diabetes, coronary heart disease, stroke, and systemic markers of C-reactive protein and interleukin-6.

PubMed

Beck, James D; Moss, Kevin L; Morelli, Thiago; Offenbacher, Steven

2018-02-01

This paper focuses on the Periodontal Profile Class (PPC) System that may be more informative and representative of periodontitis phenotypes than current case definitions of periodontitis. This study illustrates the unique aspects of the PPC compared with other periodontal indices for studying associations between periodontal disease and prevalent systemic conditions. We computed odds ratios and 95% confidence intervals to compare associations between periodontal disease and prevalent systemic conditions using our new PPC and two traditional indices. We used the Bayesian Information Criterion (BIC) to determine the fit of the model and the magnitude of the contribution attributable to periodontal disease beyond traditional risk factors. The Atherosclerosis Risk in Communities (ARIC) Study (1996-1998) results were compared with results from the combined National Health and Nutrition Examination Survey 2009-2014 datasets. In the ARIC Study, high gingival inflammation, tooth loss, severe tooth loss, and severe disease PPC components were significantly associated with diabetes, coronary heart disease (CHD), high-sensitivity C-reactive protein, and interleukin (IL)-6, while only severe disease was associated with stroke. Severe disease was associated with CHD using the Centers for Disease Control/American Academy of Periodontology index, and the European Periodontal index was associated with CHD and IL-6. The addition of the PPC to traditional variables associated with prevalent diabetes, stroke, CHD, and systemic measures of inflammation resulted in very strong improvement of the overall models, while the traditional indices were less likely to be associated and, if present, the associations were weaker. The PPC system provides specific insight into the individuals and periodontal characteristics of the phenotype that are associated with systemic conditions that may be useful in designing treatment interventions. © 2018 American Academy of Periodontology.

Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co-existent bronchiectasis.

PubMed

Perry, Elizabeth; Eggleton, Paul; De Soyza, Anthony; Hutchinson, David; Kelly, Clive

2017-12-01

Patients with rheumatoid arthritis (RA) and co-existent bronchiectasis (BRRA) have a five-fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. However, RA disease activity measures such as Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have not been studied, so we assessed these parameters in patients with BRRA and RA alone. BRRA patients (n = 53) had high-resolution computed tomography proven bronchiectasis without any interstitial lung disease and ≥ 2 respiratory infections/year. RA alone patients (n = 50) had no clinical or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor (immunoglobulin M) and anti-CCP were measured in all patients, together with detailed clinical and radiology records. In BRRA, bronchiectasis predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti-CCP (89% vs. 46%) and rheumatoid factor (79% vs. 52%) (P = 0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (P = 0.003). There were no significant differences between groups in smoking history or disease-modifying anti-rheumatic drug/biologic therapy. Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co-existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Urinary Bisphenol A Concentration and Angiography-Defined Coronary Artery Stenosis

PubMed Central

Melzer, David; Gates, Phil; Osborn, Nicholas J.; Henley, William E.; Cipelli, Ricardo; Young, Anita; Money, Cathryn; McCormack, Paul; Schofield, Peter; Mosedale, David; Grainger, David; Galloway, Tamara S.

2012-01-01

Background Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses. Methodology/Principal Findings To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n = 86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD = 5.96 ng/ml OR = 1.43, CI 1.03 to 1.98, p = 0.033), and near significant for intermediate disease (OR = 1.69, CI 0.98 to 2.94, p = 0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined. Conclusions/Significance BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established. PMID:22916252

Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder.

PubMed

Laursen, Thomas Munk; Munk-Olsen, Trine; Agerbo, Esben; Gasse, Christiane; Mortensen, Preben Bo

2009-07-01

Excess mortality from heart disease is observed in patients with severe mental disorder. This excess mortality may be rooted in adverse effects of pharmacological or psychotropic treatment, lifestyle factors, or inadequate somatic care. To examine whether persons with severe mental disorder, defined as persons admitted to a psychiatric hospital with bipolar affective disorder, schizoaffective disorder, or schizophrenia, are in contact with hospitals and undergoing invasive procedures for heart disease to the same degree as the nonpsychiatric general population, and to determine whether they have higher mortality rates of heart disease. A population-based cohort of 4.6 million persons born in Denmark was followed up from 1994 to 2007. Rates of mortality, somatic contacts, and invasive procedures were estimated by survival analysis. Incidence rate ratios of heart disease admissions and heart disease mortality as well as probability of invasive cardiac procedures. The incidence rate ratio of heart disease contacts in persons with severe mental disorder compared with the rate for the nonpsychiatric general population was only slightly increased, at 1.11 (95% confidence interval, 1.08-1.14). In contrast, their excess mortality rate ratio from heart disease was 2.90 (95% confidence interval, 2.71-3.10). Five years after the first contact for somatic heart disease, the risk of dying of heart disease was 8.26% for persons with severe mental disorder (aged <70 years) but only 2.86% in patients with heart disease who had never been admitted to a psychiatric hospital. The fraction undergoing invasive procedures within 5 years was reduced among patients with severe mental disorder as compared with the nonpsychiatric general population (7.04% vs 12.27%, respectively). Individuals with severe mental disorder had only negligible excess rates of contact for heart disease. Given their excess mortality from heart disease and lower rates of invasive procedures after first contact, it would seem that the treatment for heart disease offered to these individuals in Denmark is neither sufficiently efficient nor sufficiently intensive. This undertreatment may explain part of their excess mortality.

Assessing disease severity: accuracy and reliability of rater estimates in relation to number of diagrams in a standard area diagram set

USDA-ARS?s Scientific Manuscript database

Error in rater estimates of plant disease severity occur, and standard area diagrams (SADs) help improve accuracy and reliability. The effects of diagram number in a SAD set on accuracy and reliability is unknown. The objective of this study was to compare estimates of pecan scab severity made witho...

Symptoms of depression and anxiety in Serbian patients with systemic sclerosis: impact of disease severity and socioeconomic factors.

PubMed

Ostojic, Predrag; Zivojinovic, Sladjana; Reza, Tamara; Damjanov, Nemanja

2010-08-01

This study aimed to assess symptoms of depression and anxiety in Serbian patients with systemic sclerosis (SSc) and to estimate the impact of disease severity and socioeconomic factors on development of depression and anxiety in SSc. Thirty-five patients with SSc and 30 age- and gender-matched healthy individuals participated. Symptoms of depression and anxiety were evaluated using the Beck's depression inventory and Zung's anxiety self-assessment scale. We estimated the impact of gender, age, economic status, marital status, disease duration, disease subset (limited or diffuse), and some clinical features on development of depressive symptoms and anxiety in patients with SSc. Symptoms of depression were found in 68.6% of patients (compared with 23.3% in the control group), were more frequent in patients with longer disease duration and in female and older patients, and were more common in unemployed and retired patients than in employed individuals. No differences in anxiety and depressive symptoms was noticed between patients with limited and diffuse SSc or those with or without restrictive lung disease, pulmonary hypertension, finger-tip ulcers, and heart involvement. Symptoms of depression were associated with severe pain. Symptoms of anxiety were found in 80% of patients compared with 13.3% of healthy individuals and were equally as frequent in patients of different gender, age, socioeconomic status, and disease duration and severity. Symptoms of depression and anxiety are common in Serbian patients with SSc. Depressive symptoms depended mostly on socioeconomic factors, disease duration, and pain intensity, whereas disease severity had no significant impact on development of depressive symptoms and anxiety.

[Step Fisher discriminant analysis on severe clinical features of hand foot and mouth disease between enterovirus (EV) 71 and other EV].

PubMed

Ruan, Feng; Tan, Ai-jun; Zhang, Xue-bao; Chen, Xue-qin; Xiao, Song-jian; Ye, Zhong-wen; Wang, Song

2011-07-01

To compare the clinical features of severe hand foot and mouth disease between enterovirus (EV) 71 and other EV to find specific diagnosis index of EV71 severe hand foot and mouth disease. Case definition were adopted from national guideline of hand foot and mouth disease diagnose (Version 2010). Clinical data of severe hand foot and mouth disease came from case history and contents of questionnaire would include the ones between the time of onset and diagnoses being made. EV and EV71, Cox A16 nucleic acid tested were by RT-PCR in stool samples. Clinical features of severe hand foot and mouth disease between EV71 and other EV were compare. There appeared statistical differences between neurologic symptoms such as tremor, myoclonic jerk, listlessness, convulsion and white blood cell counts in CSF (P < 0.05). Results from the step Fisher discriminant analysis showed only tremor and white blood cell had an increase in CSF, with statistically significant differences. The discriminant equation of EV71 was Y = 3.059X(1) + 3.83X(5) - 2.742 and the equation of other EV was Y = 1.634X(1) + 1.623X(5) - 1.693. The specificity of EV71 was 91% and the specificity of other EV was 40%. The increase of clinical features of tremor and white blood cell in CSF could be used as diagnosis index of severe EV71.

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement.

PubMed

Goel, Sachin S; Agarwal, Shikhar; Tuzcu, E Murat; Ellis, Stephen G; Svensson, Lars G; Zaman, Tarique; Bajaj, Navkaranbir; Joseph, Lee; Patel, Neil S; Aksoy, Olcay; Stewart, William J; Griffin, Brian P; Kapadia, Samir R

2012-02-28

With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51-1.69; P=0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P<0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P<0.001). PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.

Periodontal disease and its connection to systemic biomarkers of cardiovascular disease in young American Indian/Alaskan natives.

PubMed

Delange, Nicole; Lindsay, Suzanne; Lemus, Hector; Finlayson, Tracy L; Kelley, Scott T; Gottlieb, Roberta A

2018-02-01

Periodontal disease has been shown to be associated with cardiovascular disease (CVD). No known studies evaluate the relationship between periodontal disease status and biomarkers of CVD risk in the American Indian/Alaskan Native (AI/AN) population despite their disproportionately high rates of poor oral health and cardiovascular disease-related outcomes. This study compared levels of interleukin (IL)-6 and C-reactive protein (CRP) across increasing severity of periodontal disease status among younger adults between the ages of 21 and 43 years. Plasma levels of IL-6 and CRP were measured in adult participants (ages 21 to 43 years) as part of a study of periodontal disease and CVD risk among an AI/AN population in southern California (n = 59). Periodontal evaluations were performed and disease status was classified into three categories based on highest probing depth (none/mild: < 3 mm; moderate: 4 to 5 mm; severe: ≥6 mm). Participants with known systemic disease or active infection were excluded. Severe periodontitis was significantly associated with increased levels of IL-6 compared with those with none or mild periodontitis before controlling for other variables (P = 0.02), but lacked significance after controlling for sex, BMI, smoking status, and high-density lipoprotein (P = 0.09). Moderate periodontal disease was positively associated with IL-6 levels after controlling for potential confounders (P = 0.01). Periodontal status was not associated with CRP, before or after adjusting for covariates. In this otherwise healthy AI/AN adult sample, moderate periodontal disease compared with none or mild periodontal disease was associated with increased levels of IL-6. High levels of CRP found in this population warrant further research. © 2018 American Academy of Periodontology.

Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT.

PubMed

Ciet, Pierluigi; Serra, Goffredo; Bertolo, Silvia; Spronk, Sandra; Ros, Mirco; Fraioli, Francesco; Quattrucci, Serena; Assael, M Baroukh; Catalano, Carlo; Pomerri, Fabio; Tiddens, Harm A W M; Morana, Giovanni

2016-03-01

To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100% (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). PROPELLER MRI does not match CT sensitivity to assess CF lung disease. PROPELLER MRI has lower sensitivity than CT to detect severe bronchiectasis. PROPELLER MRI has good to very good intra- and inter-observer variability. PROPELLER MRI can be used for short-term follow-up studies in CF.

Plus Disease in Retinopathy of Prematurity: Diagnostic Trends in 2016 vs. 2007

PubMed Central

Moleta, Chace; Campbell, J. Peter; Kalpathy-Cramer, Jayashree; Chan, RV Paul; Ostmo, Susan; Jonas, Karyn; Chiang, Michael F.

2017-01-01

Purpose To identify any temporal trends in the diagnosis of plus disease in retinopathy of prematurity (ROP) by experts. Design Reliability analysis Methods ROP experts were recruited in 2007 and 2016 to classify 34 wide-field fundus images of ROP as plus, pre-plus, or normal, coded as “3,” “2,” and “1” respectively in the database. The main outcome was the average calculated score for each image in each cohort. Secondary outcomes included correlation on the relative ordering of the images in 2016 versus 2007, inter-expert agreement, and intra-expert agreement Results The average score for each image was higher for 30/34 (88%) images in 2016 compared to 2007, influenced by fewer images classified as normal (P<0.01), a similar number of pre-plus (P=0.52), and more classified as plus (P<0.01). The mean weighted kappa values in 2006 were 0.36 (range 0.21 – 0.60) compared to 0.22 (range 0 – 0.40) in 2016. There was good correlation between rankings of disease severity between the two cohorts (Spearman’s rank correlation ρ=0.94) indicating near-perfect agreement on relative disease severity. Conclusions Despite good agreement between cohorts on relative disease severity ranking, the higher average score and classifications for each image demonstrate that experts are diagnosing pre-plus and plus disease at earlier stages of disease severity in 2016, compared with 2007. This has implications for patient care, research, and teaching, and additional studies are needed to better understand this temporal trend in image-based plus disease diagnosis. PMID:28087400

Perceived threat, risk perception, and efficacy beliefs related to SARS and other (emerging) infectious diseases: results of an international survey.

PubMed

de Zwart, Onno; Veldhuijzen, Irene K; Elam, Gillian; Aro, Arja R; Abraham, Thomas; Bishop, George D; Voeten, Hélène A C M; Richardus, Jan Hendrik; Brug, Johannes

2009-01-01

To study the levels of perceived threat, perceived severity, perceived vulnerability, response efficacy, and self-efficacy for severe acute respiratory syndrome (SARS) and eight other diseases in five European and three Asian countries. A computer-assisted phone survey was conducted among 3,436 respondents. The questionnaire focused on perceived threat, vulnerability, severity, response efficacy, and self-efficacy related to SARS and eight other diseases. Perceived threat of SARS in case of an outbreak in the country was higher than that of other diseases. Perceived vulnerability of SARS was at an intermediate level and perceived severity was high compared to other diseases. Perceived threat for SARS varied between countries in Europe and Asia with a higher perceived severity of SARS in Europe and a higher perceived vulnerability in Asia. Response efficacy and self-efficacy for SARS were higher in Asia compared to Europe. In multiple linear regression analyses, country was strongly associated with perceived threat. The relatively high perceived threat for SARS indicates that it is seen as a public health risk and offers a basis for communication in case of an outbreak. The strong association between perceived threat and country and different regional patterns require further research.

Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study.

PubMed

Pfitscher, L C; Cecatti, J G; Pacagnella, R C; Haddad, S M; Parpinelli, M A; Souza, J P; Quintana, S M; Surita, F G; Sousa, M H; Costa, M L

2016-05-21

The aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome. A multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling. Among 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7. Respiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

Hispanic Americans and African Americans with multiple sclerosis have more severe disease course than Caucasian Americans.

PubMed

Ventura, Rachel E; Antezana, Ariel O; Bacon, Tamar; Kister, Ilya

2017-10-01

Whether disease course in Hispanic Americans (HA) with multiple sclerosis (MS) is different from Caucasian Americans (CA) or African Americans (AA) is unknown. We compared MS severity in the three main ethnic populations in our tertiary MS clinics using disease duration-adjusted rank score of disability: Patient-Derived Multiple Sclerosis Severity Score (P-MSSS). The age- and gender-adjusted P-MSSS was significantly higher in HA (3.9 ± 2.6) and AA (4.5 ± 3.0) compared to CA (3.4 ± 2.6; p < 0.0001 for both). Adjusting for insurance did not change these results. These findings suggest that HA, as AA, have more rapid disability accumulation than CA.

Cough is less common and less severe in systemic sclerosis-associated interstitial lung disease compared to other fibrotic interstitial lung diseases.

PubMed

Cheng, Jasmine Z; Wilcox, Pearce G; Glaspole, Ian; Corte, Tamera J; Murphy, Darra; Hague, Cameron J; Ryerson, Christopher J

2017-11-01

The objectives of this study were to determine the prevalence and characteristics of cough in idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP) and systemic sclerosis-associated interstitial lung disease (SSc-ILD). Cough severity was measured in consecutive patients with IPF (n = 77), HP (n = 32) and SSc-ILD (n = 67) using a 10-cm visual analogue scale (VAS). Dyspnoea and quality of life were measured using established questionnaires. Cough severity was compared across ILD subtypes and predictors of cough severity were determined using multivariate analysis. Cough was more common in IPF and chronic HP compared to SSc-ILD (87% and 83% vs 68%, P = 0.02). The median (interquartile range) VAS score was 39 (17-65) in the IPF cohort, 29 (11-48) in HP and 18 (0-33) in SSc-ILD (P < 0.0001). Cough was more often productive in chronic HP and IPF (63% and 43% vs 21%, P < 0.001). Cough severity was independently predicted only by ILD diagnosis and higher dyspnoea score. Cough severity was not associated with other common causes of cough. Cough was a significant predictor of quality of life in IPF and SSc-ILD with adjustment for age, sex, dyspnoea and ILD severity; however, cough was not associated with quality of life in chronic HP. Cough is more frequent, more severe and more often productive in IPF and chronic HP compared to SSc-ILD, despite similar ILD severity in these cohorts. Cough severity is strongly and independently associated with dyspnoea and pulmonary function, and is a significant contributor to reduced quality of life in both IPF and SSc-ILD. © 2017 Asian Pacific Society of Respirology.

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients.

PubMed

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. This was a case-control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e': 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function.

Increased severity in patients presenting to hospital with diarrhea in Dhaka, Bangladesh Since emergence of the hybrid strain of Vibrio cholerae O1 is not unique to cholera patients

PubMed Central

Chowdhury, Fahima; Kuchta, Alison; Khan, Ashraful Islam; Faruque, ASG; Calderwood, Stephen B.; Ryan, Edward T.; Qadri, Firdausi

2015-01-01

In 2001, a hybrid strain of Vibrio cholerae O1 El Tor that expresses a classical cholera toxin (CT) emerged and this hybrid variant rapidly replaced the previous El Tor strain around the world. The global emergence of this variant coincided with anecdotal reports that cholera patients were presenting with more severe dehydration and disease in many locations. We compared severity of disease in cholera patients from before and after emergence of the hybrid strain at a diarrheal hospital in Dhaka, Bangladesh. We did indeed find that cholera patients presented with more severe dehydration and severe disease in the latter period; however, this was also true for “all non-cholera patients” as well. In addition, in sub-analyses of patients who presented with rotavirus and enterotoxigenic E. coli (ETEC), we found similar results. Comparing the two periods for differences in patient characteristics, nutritional status, vaccination status and income, we were unable to detect a plausible cause for patients presenting with more severe disease in the latter period. Because we observed a shift in severity for both cholera and non-cholera, our results indicate that the altered El Tor strain cannot fully explain the differences in cholera severity before and after 2001 PMID:26409202

A Role for Neutrophils in Viral Respiratory Disease.

PubMed

Camp, Jeremy V; Jonsson, Colleen B

2017-01-01

Neutrophils are immune cells that are well known to be present during many types of lung diseases associated with acute respiratory distress syndrome (ARDS) and may contribute to acute lung injury. Neutrophils are poorly studied with respect to viral infection, and specifically to respiratory viral disease. Influenza A virus (IAV) infection is the cause of a respiratory disease that poses a significant global public health concern. Influenza disease presents as a relatively mild and self-limiting although highly pathogenic forms exist. Neutrophils increase in the respiratory tract during infection with mild seasonal IAV, moderate and severe epidemic IAV infection, and emerging highly pathogenic avian influenza (HPAI). During severe influenza pneumonia and HPAI infection, the number of neutrophils in the lower respiratory tract is correlated with disease severity. Thus, comparative analyses of the relationship between IAV infection and neutrophils provide insights into the relative contribution of host and viral factors that contribute to disease severity. Herein, we review the contribution of neutrophils to IAV disease pathogenesis and to other respiratory virus infections.

A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan.

PubMed

Bekolo, Cavin Epie; van Loenhout, Joris Adriaan Frank; Rodriguez-Llanes, Jose Manuel; Rumunu, John; Ramadan, Otim Patrick; Guha-Sapir, Debarati

2016-09-01

To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South Sudan on patients who developed cholera disease between 23 April and 20 July 2014 during a large outbreak, a few months after a pre-emptive oral vaccination campaign. Patients who developed severe dehydration were regarded as having a severe cholera infection. Vaccinated and unvaccinated patients were compared and multivariate logistic regression analysis was used to identify factors associated with developing severe disease or death. In total, 4115 cholera patients were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%) deaths occurred. Multivariate analysis showed that patients who received two doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). Pre-emptive vaccination with two doses of oral cholera vaccine was associated with a significant reduction in the likelihood of developing severe cholera disease during an outbreak in South Sudan. Moreover, severe disease was the strongest predictor of death. Two doses of oral cholera vaccine should be used in emergencies to reduce the disease burden.

NON-INFECTIOUS DISORDERS OF WARMWATER FISHES

EPA Science Inventory

Compared with infectious diseases and disorders, few non-infectious diseases and disorders in cultured fish have severe biologic or economic impact. Culture practices, however, often establish environments that promote infectious disease by weakening the immune response or by pro...

Extraintestinal manifestations were common in children with coeliac disease and were more prevalent in patients with more severe clinical and histological presentation.

PubMed

Nurminen, Samuli; Kivelä, Laura; Huhtala, Heini; Kaukinen, Katri; Kurppa, Kalle

2018-03-22

This study investigated the prevalence of extraintestinal manifestations (EIM) in paediatric coeliac disease and their associations with other disease features. Researchers at the University of Tampere, Finland, compared EIM in 511 children diagnosed with coeliac disease from 2003 to 2014 and 180 diagnosed with functional gastrointestinal disorders from 2007 to 2013. Disease severity and dietary responses were also compared between coeliac children diagnosed by screening (n = 146) or because of EIM (n = 116) or gastrointestinal symptoms (n = 249). Coeliac patients had more EIM (62%) than those with functional disorders (33%). The most common EIM in coeliac children were poor growth (27%) and anaemia (18%). Children with coeliac disease often showed fatigue (8%) and symptoms affecting the skin (15%), nervous system (9%) and joints (6%). Coeliac patients with EIM as their main clinical presentation had more severe symptoms and histological damage at diagnosis than those with gastrointestinal presentation and screen-detected cases. The subgroups did not differ with regard to other clinical and laboratory parameters and dietary adherence. Concomitant EIM were also common in children diagnosed because of gastrointestinal presentation (60%) and by screening (37%). EIM were common in coeliac disease and associated with more severe clinical and histological presentation. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Disadvantages of the Horsfall-Barratt Scale for estimating severity of citrus canker

USDA-ARS?s Scientific Manuscript database

Direct visual estimation of disease severity to the nearest percent was compared to using the Horsfall-Barratt (H-B) scale. Data from a simulation model designed to sample two diseased populations were used to investigate the probability of the two methods to reject a null hypothesis (H0) using a t-...

Evaluation of the association between Hispanic ethnicity and disease activity and severity in a large cohort of patients with juvenile idiopathic arthritis.

PubMed

Pelajo, Christina F; Angeles-Han, Sheila T; Prahalad, Sampath; Sgarlat, Caitlin M; Davis, Trevor E; Miller, Laurie C; Lopez-Benitez, Jorge M

2013-10-01

To examine the association between ethnicity and disease activity in patients with juvenile idiopathic arthritis (JIA), and to determine the association of ethnicity with disease severity and disability in this population. CARRAnet, a US database containing information (collected between May 2010 and June 2011) on almost 3,000 subjects with JIA, was used. Demographic variables were compared between Hispanic patients and non-Hispanic patients. Mann-Whitney and chi-square tests were used to compare indicators of disease activity, as well as imaging evidence of joint damage, and Childhood Health Assessment Questionnaire (CHAQ) scores between ethnicities. Two linear regression models were used to determine the association of ethnicity with number of active joints in JIA, and the association between ethnicity and disability (CHAQ scores). A total of 2,704 patients with JIA (277 Hispanic; 2,427 non-Hispanic) were included. Income and health insurance coverage were higher in non-Hispanics. RF-positive polyarticular JIA, positive RF and anti-CCP, as well as use of systemic steroids were more frequent in Hispanics. Imaging evidence of joint damage was present in 32 % of the Hispanic patients compared to 24 % of the non-Hispanic patients (p = 0.008). In multivariate linear regression analyses, the number of active joints was significantly higher in Hispanics than in non-Hispanics (p = 0.03), as well as CHAQ scores (p = 0.003), after adjusting for confounders. Hispanic patients with JIA had higher disease activity than non-Hispanic patients, as well as higher disease severity and disability. Since ethnicity influences disease activity, severity, and disability, different management and treatment plans should be planned accordingly.

Severe streptococcal infections in historical perspective.

PubMed

Katz, A R; Morens, D M

1992-01-01

The recent unexplained increase in severe streptococcal diseases in the United States and Great Britain is compared to the 1825-1885 pandemic of fatal scarlet fever. Although scarlet fever may not be representative of all severe streptococcal disease, it was the only one reliably identified in the 19th century. The epidemiology of scarlet fever during the 19th century pandemic suggests the following features of the disease; cocirculation of both virulent and less-virulent streptococcal strains eliciting cross-immunity; circulation of hyperendemic prevalent strains in urban centers of developed nations, with periodic spillovers to rural areas and developing nations; and protection of infants from infection (but not from fatal disease once infection occurred) by the transfer of maternal antibodies via the placenta, breast milk, or both. The 19th century data suggest that efforts to prevent severe streptococcal diseases should begin with better characterization of the epidemiology of streptococcal disease, a task entailing identification of streptococcal virulence factors and measurement of their distribution among isolates from individuals with streptococcal diseases and in open populations.

Murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects disease severity.

PubMed

Ljungvall, I; Rishniw, M; Porciello, F; Ferasin, L; Ohad, D G

2014-11-01

To determine whether murmur intensity in small-breed dogs with myxomatous mitral valve disease reflects clinical and echocardiographic disease severity. Retrospective multi-investigator study. Records of adult dogs Ä20 kg with myxomatous mitral valve disease were examined. Murmur intensity and location were recorded and compared with echocardiographic variables and functional disease status. Murmur intensities in consecutive categories were compared for prevalences of congestive heart failure, pulmonary hypertension and cardiac remodelling. 578 dogs [107 with "soft" (30 Grade I/VI and 77 II/VI), 161 with "moderate" (Grade III/VI), 160 with "loud" (Grade IV/VI) and 150 with "thrilling" (Grade V/VI or VI/VI) murmurs] were studied. No dogs with soft murmurs had congestive heart failure, and 90% had no remodelling. However, 56% of dogs with "moderate", 29% of dogs with "loud" and 8% of dogs with "thrilling" murmurs and subclinical myxomatous mitral valve disease also had no remodelling. Probability of a dog having congestive heart failure or pulmonary hypertension increased with increasing murmur intensity. A 4-level murmur grading scheme separated clinically meaningful outcomes in small-breed dogs with myxomatous mitral valve disease. Soft murmurs in small-breed dogs are strongly indicative of subclinical heart disease. Thrilling murmurs are associated with more severe disease. Other murmurs are less informative on an individual basis. © 2014 British Small Animal Veterinary Association.

Activation of cellular immune response in acute pancreatitis.

PubMed Central

Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G

1997-01-01

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935

Subanalysis of the CONFIRM Registries: Acute Procedural Outcomes in Claudicant and Critical Limb Ischemia Patients With Varying Levels of Calcification Treated for Peripheral Arterial Disease With Orbital Atherectomy.

PubMed

Adams, George L; Das, Tony; Lee, Michael S; Beasley, Robert; Mustapha, Jihad

2015-11-01

Patients with peripheral arterial disease (PAD) can be classified into groups based upon the severity of the disease using the Rutherford classification system. This analysis compares the procedural outcomes of PAD patients treated with orbital atherectomy stratified by Rutherford class (1-3 = intermittent claudication; 4-6 = critical limb ischemia [CLI]), and acute angiographic outcomes of these patients stratified by degree of lesion calcification. The CONFIRM registry series was analyzed and included 1697 patients with intermittent claudication (Rutherford class 1-3) and 1320 patients with CLI (Rutherford class 4-6) treated with orbital atherectomy. The composite rate of dissection, perforation, slow-flow, vessel closure, spasm, embolism, and thrombus formation was compared between claudicants and CLI patients with varying degrees of lesion calcification. Patients with CLI were older and had a higher prevalence of diabetes, coronary artery disease, and renal disease (P<.001). Claudicants with moderately/severely calcified lesions had a lower rate of dissection (both non-flow limiting and flow-limiting) than claudicants with mildly/minimally calcified lesions. CLI patients with mildly/minimally calcified lesions had higher rates of embolism and thrombus than CLI patients with moderately/severely calcified lesions. Plaque modification with orbital atherectomy resulted in similar low procedural complication rates in the CLI group compared with the claudicant group. These results suggest that orbital atherectomy is safe and effective for treating calcified lesions in high-risk patients with varying severity of PAD symptoms.

Association of heart rate profile during exercise with the severity of coronary artery disease.

PubMed

Cay, Serkan; Ozturk, Sezgin; Biyikoglu, Funda; Yildiz, Abdulkadir; Cimen, Tolga; Uygur, Belma; Tuna, Funda

2009-05-01

Coronary artery disease is the leading cause of morbidity and mortality around the world. Autonomic nervous system abnormalities are associated with coronary artery disease and its complications. Exercise stress tests are routinely used for the detection of the presence of coronary artery disease. In this study, we observed the association between heart rate profile during exercise and the severity of coronary artery disease. One hundred and sixty patients with abnormal exercise treadmill test (> or =1 mm horizontal or downsloping ST-segment depression; 119 men, 41 women; mean age = 57 +/- 9 years) were included in the study. Use of any drug affecting heart rate was not permitted. Resting heart rate before exercise, maximum heart rate during exercise, and resting heart rate after exercise (5 min later) were measured and two parameters were calculated: heart rate increment (maximum heart rate - resting heart rate before exercise) and heart rate decrement (maximum heart rate - resting heart rate after exercise). All patients underwent selective coronary angiography and subclassified into two groups according to stenotic lesion severity. Group 1 had at least 50% of stenotic lesion and group 2 had less than 50%. Patients in the first group had increased resting heart rate, decreased maximum heart rate, decreased heart rate increment, and decreased heart rate decrement compared with second group. All patients were classified into tertiles of resting heart rate, heart rate increment, and heart rate decrement level to evaluate whether these parameters were associated with severity of coronary artery stenosis in the study. The multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 21.888 (95% confidence interval 6.983-68.606) for the highest tertile of resting heart rate level compared with the lowest tertile. In addition, the multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 20.987 (95% confidence interval 6.635-66.387) for the lowest tertile of heart rate increment level compared with the highest tertile and 2.360 (95% confidence interval 1.004-5.544) for the lowest tertile of heart rate decrement level compared with the highest tertile. Altered autonomic nervous system regulation affects heart rate profile, increased resting heart rate, decreased heart rate increment, and decreased heart rate decrement, during exercise and this effect is strongly and independently associated with the severity of coronary artery disease.

Crystal-proven Gout and Characteristic Gout Severity Factors are Associated with Cardiovascular Disease.

PubMed

Disveld, Iris J M; Fransen, Jaap; Rongen, Gerard A; Kienhorst, Laura B E; Zoakman, Sahel; Janssens, Hein J E M; Janssen, Matthijs

2018-04-15

Our aim was to examine the prevalence of cardiovascular disease (CVD) in patients with crystal-proven gout compared to arthritis controls. Further, we analyzed the association between characteristic gout severity factors and CVD to provide further support for a pathogenetic relationship between gout and CVD. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in all referred patients; controls were negative for crystals. Patients' characteristics and different manifestations of CVD and gout severity factors (disease duration, attack frequency, tophi, affected joints, high serum urate acid level, joint damage) were collected. Gout patients were compared with controls for the prevalence of CVD. In addition, the association between characteristic gout severity factors and presence of CVD was analyzed. Data from 700 gout patients and 276 controls were collected. CVD was present in 47% (95% CI 44%-51%) and 24% (95% CI 19%-29%) of gout patients and controls, respectively. Corrected for confounders, gout was still strongly associated with an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37-4.84). In patients with gout, disease duration ≥ 2 years, oligo- or polyarthritis, serum urate acid > 0.55 mmol/l at presentation, and joint damage were independently (p < 0.05) associated with prevalent CVD. Crystal-proven gout was strongly associated with an increased prevalence of CVD. In patients with gout, characteristic gout severity factors were associated with CVD.

Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients

PubMed Central

Huang, Ying-Shuo; Feng, Ying-Chao; Zhang, Jian; Bai, Li; Huang, Wei; Li, Min; Sun, Ying

2015-01-01

Objective To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients. Methods This was a case–control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared. Results Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e′: 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05). Conclusion Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function. PMID:25565790

CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.

PubMed

Rojas, Julio C; Bang, Jee; Lobach, Iryna V; Tsai, Richard M; Rabinovici, Gil D; Miller, Bruce L; Boxer, Adam L

2018-01-23

To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). We compared the ability of baseline CSF β-amyloid 1-42 , tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients. Higher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS ( p = 0.004, false discovery rate-corrected) and SEADL ( p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS ( p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL ( p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau ( p = 0.003) or NfL ( p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively). Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease. Copyright © 2017 American Academy of Neurology.

Determining the diagnostic value of endogenous carbon monoxide in chronic obstructive pulmonary disease exacerbations.

PubMed

Dogan, Nurettin Özgür; Corbacioglu, Seref Kerem; Bildik, Fikret; Kilicaslan, Isa; Günaydin, Gül Pamukcu; Cevik, Yunsur; Ülker, Volkan; Hakoglu, Onur; Gökcen, Emre

2014-09-01

To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p < 0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95- 2.00). The corresponding levels in Group 2 (1.8 [1.38-2.20]) and Group 3 (1.9 [1.5-3.0]) were higher than the controls (p < 0.001 and p < 0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 [1.10-1.55]) was observed (p < 0.434). Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations.

Long-term effectiveness of rivastigmine patch or capsule for mild-to-severe Alzheimer's disease: a meta-analysis.

PubMed

Su, Jiangli; Liu, Yang; Liu, Yu; Ren, Liqun

2015-01-01

To evaluate the long-term effectiveness of rivastigmine patch or capsule on mild to severe Alzheimer's disease (AD). We performed a meta-analysis of 17 studies regarding the treatment effectiveness of rivastigmine patch or capsule on mild-to-severe AD. Significant difference exists between treatment with rivastigmine patch or capsule and placebo groups (p-value < 0.001). In the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score evaluation, a negative weighted mean difference (WMD) was observed in overall and mild-moderate groups after rivastigmine treatment. And in ADAS-ADL score evaluation, a positive WMD was observed in overall groups after rivastigmine treatment. Moreover, WMD value is lower in patch administration subgroup compared to that of capsule administration subgroup. Rivastigmine treatment shows a positive result of improving the condition of patients with mild-to-severe AD. Patch administration shows a stronger effect on decreasing ADAS-Cog score compared to capsule administration.

Nitric Oxide-Dependent Endothelial Dysfunction and Reduced Arginine Bioavailability in Plasmodium vivax Malaria but No Greater Increase in Intravascular Hemolysis in Severe Disease.

PubMed

Barber, Bridget E; William, Timothy; Grigg, Matthew J; Piera, Kim A; Chen, Youwei; Wang, Hao; Weinberg, J Brice; Yeo, Tsin W; Anstey, Nicholas M

2016-11-15

 Pathogenesis of severe Plasmodium vivax malaria is poorly understood. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability characterize severe falciparum malaria, but have not been assessed in severe vivax malaria.  In patients with severe vivax malaria (n = 9), patients with nonsevere vivax malaria (n = 58), and healthy controls (n = 79), we measured NO-dependent endothelial function by using reactive hyperemia-peripheral arterial tonometry (RH-PAT) and assessed associations with arginine, asymmetric dimethylarginine (ADMA), and hemolysis.  The L-arginine level and the L-arginine to ADMA ratio (a measure of L-arginine bioavailability) were reduced in patients with severe vivax malaria and those with nonsevere vivax malaria, compared with healthy controls (median L-arginine level, 65, 66, and 98 µmol/mL, respectively [P = .0001]; median L-arginine to ADMA ratio, 115, 125, and 187, respectively [P = .0001]). Endothelial function was impaired in proportion to disease severity (median RH-PAT index, 1.49, 1.73, and 1.97 in patients with severe vivax malaria, those with nonsevere vivax malaria, and healthy controls, respectively; P = .018) and was associated with the L-arginine to ADMA ratio. While the posttreatment fall in hemoglobin level was greater in severe vivax malaria as compared to nonsevere vivax malaria (2.5 vs 1 g/dL; P = .0001), markers of intravascular hemolysis were not higher in severe disease.  Endothelial function is impaired in nonsevere and severe vivax malaria, is associated with reduced L-arginine bioavailability, and may contribute to microvascular pathogenesis. Severe disease appears to be more associated with extravascular hemolysis than with intravascular hemolysis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

PubMed

Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

2014-12-01

Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity. © ISFM and AAFP 2014.

Association between chronic azotemic kidney disease and the severity of periodontal disease in dogs.

PubMed

Glickman, Lawrence T; Glickman, Nita W; Moore, George E; Lund, Elizabeth M; Lantz, Gary C; Pressler, Barrak M

2011-05-01

Naturally occurring periodontal disease affects >75% of dogs and has been associated with cardiac lesions and presumptive endocarditis. However, the relationships between periodontal disease and chronic kidney disease (CKD) in dogs have not been studied. In a retrospective longitudinal study the incidence of azotemic CKD was compared between a cohort of 164,706 dogs with periodontal disease and a cohort of age-matched dogs with no periodontal disease from a national primary care practice. These dogs contributed 415,971 dog-years of follow-up from 2002 to 2008. Hazard ratios and 95% confidence intervals from Cox regression were used to compare the incidence of azotemic CKD in dogs with stage 1, 2, or 3/4 periodontal disease to dogs with no periodontal disease. The hazard ratio for azotemic CKD increased with increasing severity of periodontal disease (stage 1 hazard ratio=1.8, 95% confidence interval: 1.6, 2.1; stage 2 hazard ratio=2.0, 95% confidence interval: 1.7, 2.3; stage 3/4 hazard ratio=2.7, 95% confidence interval: 2.3, 3.0; P(trend)=<0.0001) after adjustment for age, gender, neuter status, breed, body weight, number of hospital visits, and dental procedures. Increasing severity of periodontal disease was also associated with serum creatinine >1.4 mg/dl and blood urea nitrogen >36 mg/dl, independent of a veterinarian's clinical diagnosis of CKD. Copyright © 2011 Elsevier B.V. All rights reserved.

Relation of antioxidant status at admission and disease severity and outcome in dogs naturally infected with Babesia canis canis.

PubMed

Crnogaj, Martina; Cerón, José Joaquin; Šmit, Iva; Kiš, Ivana; Gotić, Jelena; Brkljačić, Mirna; Matijatko, Vesna; Rubio, Camila Peres; Kučer, Nada; Mrljak, Vladimir

2017-04-24

Canine babesiosis is caused by species of the Babesia genus and has become an emerging disease worldwide. To the authors' knowledge there are no reports in which antioxidants have been analyzed in different presentations of canine babesiosis or in which the prognostic value of antioxidants has been studied. The aim of this study was to evaluate whether oxidative stress could be related to the severity and outcome of canine babesiosis. For this purpose a profile consisting of four antioxidant biomarkers (superoxide dismutase - SOD, glutathione peroxidase - GPx, catalase, total antioxidant status - TAS) and malondialdehyde - MDA as an oxidant biomarker (previously evaluated, here studied for comparative purposes) were evaluated in dogs with canine babesiosis of different clinical severity and outcomes. The study was conducted with a sample of 40 dogs suffering from babesiosis (further divided into uncomplicated, one complication and multiple organ dysfunction syndrome - MODS group) and 30 healthy dogs (control group). Additionally, the babesiosis group was divided according to the anaemia into non-anaemic, mildly anaemic, moderately anaemic and severely anaemic dogs. The results of our study showed significantly decreased SOD, catalase and TAS values in diseased dogs compared to controls, while there were no significant differences in GPx between these groups. Dogs that developed MODS showed lower activities of SOD and GPx and higher MDA values compared to dogs with uncomplicated babesiosis as well as with dogs that developed one complication. Superoxide dismutase, catalase and GPx were negatively correlated whereas MDA was positively correlated with the lethal outcome of the disease. Furthermore, this study detected more pronounced decrease in antioxidant biomarkers (SOD, GPx and catalase) in dogs with moderate anaemia compared to those with mild anaemia. The results of this study showed changes in biomarkers related to the antioxidant status of dogs naturally infected with B. canis canis. These biomarkers could be used as indicators of disease severity and outcome in dogs suffering from babesiosis.

Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria.

PubMed

te Witt, René; van Wolfswinkel, Marlies E; Petit, Pieter L; van Hellemond, Jaap J; Koelewijn, Rob; van Belkum, Alex; van Genderen, Perry J J

2010-09-14

Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported malaria. In the present study, the diagnostic accuracy of plasma soluble Triggering Receptor Expressed on Myeloid cells 1 (TREM-1), neopterin and procalcitonin levels as biomarkers for severe Plasmodium falciparum disease was evaluated in 104 travellers with imported malaria (26 patients with non-P. falciparum malaria, 64 patients with uncomplicated P. falciparum malaria and 14 patients with severe P. falciparum malaria). TREM-1, neopterin and procalcitonin were determined in serum using commercially available ELISA or EIA tests. The diagnostic performance of these biomarkers for severe disease was compared with plasma lactate, a well-validated parameter for disease severity in patients with malaria, as reference. Severe malaria was defined according to the modified WHO criteria. No significant differences in TREM-1 levels were detected between the different patient groups. Patients with severe P. falciparum malaria had significantly higher neopterin and procalcitonin levels on admission when compared to patients with uncomplicated P. falciparum malaria or non-P. falciparum malaria. Receiver Operating Characteristic (ROC) curve analysis showed that neopterin had the highest Area-Under-the-ROC curve (AUROC 0.85) compared with plasma lactate (AUROC 0.80) and procalcitonin (AUROC 0.78). At a cut-off point of 10.0 ng/ml, neopterin had a positive and negative predictive value of 0.38 and 0.98 whereas procalcitonin, at a cut-off point of 0.9 ng/ml, had a positive and negative predictive value of 0.30 and 1.00. Although the diagnostic value of neopterin and procalcitonin is limited, the high negative predictive value of both neopterin and procalcitonin may be helpful for a rapid exclusion of severe malaria disease on admission. This may be a valuable tool for physicians only occasionally dealing with ill-returned travellers from malaria-endemic regions and who need to decide on subsequent oral anti-malarial treatment or timely referral to a specialized centre for high-level monitoring and intensified parenteral treatment.

Predictors of Olfactory Dysfunction in Rhinosinusitis Using the Brief Smell Identification Test

PubMed Central

Alt, Jeremiah A.; Mace, Jess C.; Buniel, Maria C. F.; Soler, Zachary M.; Smith, Timothy L.

2014-01-01

Objective Associations between olfactory function to quality-of-life (QOL) and disease severity in patients with rhinosinusitis is poorly understood. We sought to evaluate and compare olfactory function between subgroups of patients with rhinosinusitis using the Brief Smell Identification Test (BSIT). Study Design Cross-sectional evaluation of a multi-center cohort. Methods Patients with recurrent acute sinusitis (RARS) and chronic rhinosinusitis (CRS) with and without nasal polyposis were prospectively enrolled from three academic tertiary care sites. Each subject completed the BSIT, in addition to measures of disease-specific QOL. Patient demographics, comorbidities, and clinical measures of disease severity were compared between patients with normal (BSIT; ≥9) and abnormal (BSIT; <9) olfaction scores. Regression modeling was used to identify potential risk factors associated with olfactory impairment. Results Patients with rhinosinusitis (n=445) were found to suffer olfactory dysfunction as measured by the BSIT (28.3%). Subgroups of rhinosinusitis differed in the degree of olfactory dysfunction reported. Worse disease severity, measured by computed tomography and nasal endoscopy, correlated to worse olfaction. Olfactory scores did not consistently correlate with Rhinosinusitis Disability Index or Sinonasal Outcome Test scores. Regression models demonstrated nasal polyposis was the strongest predictor of olfactory dysfunction. Recalcitrant disease and aspirin intolerance were strongly predictive of worse olfactory function. Conclusion Olfactory dysfunction is a complex, multi-factorial process found to be differentially expressed within subgroups of rhinosinusitis. Olfaction was associated with disease severity as measured by imaging and endoscopy, with only weak associations to disease-specific QOL measures. PMID:24402746

Pulmonary MR imaging with ultra-short TEs: utility for disease severity assessment of connective tissue disease patients.

PubMed

Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; van Cauteren, Marc; Sugimura, Kazuro

2013-08-01

To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2 maps were generated from each MR data set, and mean T2 values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2 values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2 values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Mean T2 values for normal and CTD subjects were significantly different (p=0.0019) and showed significant correlations with %VC, %DLCO, serum KL-6 and CT-based disease severity of CTD patients (p<0.05). Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pragmatic communication is impaired in Parkinson disease.

PubMed

Hall, Deborah; Ouyang, Bichun; Lonnquist, Eryn; Newcombe, Jill

2011-05-01

The purpose of this study was to determine whether severity of disease, cognitive function, age, gender, or amount of social interaction were associated with pragmatic dysfunction in Parkinson disease. No studies have previously been done to investigate variables that may be associated with pragmatic dysfunction in Parkinson disease. A case-control study was conducted with 17 Parkinson disease patients and 17 convenience controls. Each Parkinson disease patient and a control were interviewed, and their pragmatic skills were evaluated using a scale of pragmatic communication skills. Correlation analysis was used to determine what factors were associated with pragmatic dysfunction in the Parkinson disease patients. Cases scored lower on the pragmatic scale with a mean of 29.7 compared with 38.9 in the controls (p < .001) out of 40 possible points. The score on the scale of pragmatic communication skills had moderate to strong correlations with the MMSE (r = .81, p = .002), Unified Parkinson's Disease Rating Scale score (r = -.71, p = .002), and duration of disease (r = -.53, p = .03). These results show that Parkinson disease patients have impaired pragmatic function compared with controls on both verbal and nonverbal sections, and this impairment correlates with mental state, duration, and severity of disease.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

PubMed

Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

2017-02-01

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study.

PubMed

Hagström, Hannes; Nasr, Patrik; Ekstedt, Mattias; Hammar, Ulf; Stål, Per; Hultcrantz, Rolf; Kechagias, Stergios

2018-01-01

Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI < 25.0), overweight (BMI 25.0-29.9), or obese (BMI ≥ 30.0) at the time of biopsy. Each case was matched for age, sex, and municipality to 10 controls. Overall mortality and development of severe liver disease were evaluated using population-based registers. Cox regression models adjusted for age, sex, type 2 diabetes, and fibrosis stage were used to examine the long-term risk of mortality and liver-related events in lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion : Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. ( Hepatology Communications 2018;2:48-57).

Impulsive-compulsive behaviors in parkin-associated Parkinson disease.

PubMed

Morgante, Francesca; Fasano, Alfonso; Ginevrino, Monia; Petrucci, Simona; Ricciardi, Lucia; Bove, Francesco; Criscuolo, Chiara; Moccia, Marcello; De Rosa, Anna; Sorbera, Chiara; Bentivoglio, Anna Rita; Barone, Paolo; De Michele, Giuseppe; Pellecchia, Maria Teresa; Valente, Enza Maria

2016-10-04

The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was adopted to rate ICB severity. Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score. Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity. © 2016 American Academy of Neurology.

Simple repair approach for mitral regurgitation in Barlow disease.

PubMed

Ben Zekry, Sagit; Spiegelstein, Dan; Sternik, Leonid; Lev, Innon; Kogan, Alexander; Kuperstein, Rafael; Raanani, Ehud

2015-11-01

Mitral valve repair for myxomatous Barlow disease is a challenging procedure requiring complex surgery with less than optimal results. The use of ring-only repair has been previously reported but never analyzed or followed-up. We investigated this simple valve repair approach for patients with Barlow disease and multisegment involvement causing mainly central jet. Of 572 patients who underwent mitral valve repair for mitral regurgitation at our medical center, 24 with Barlow disease (aged 47 ± 14 years; 46% male) underwent ring-only repair. Patients were characterized by severely enlarged mitral valve annulus, multisegment prolapse involving both leaflets, and demonstrated mainly a central wide regurgitant jet. Surgical technique included only the implantation of a large mitral annuloplasty ring. Early and late outcome results were compared with those of the remaining patients who underwent conventional mitral valve repair for degenerative disease (controls). All ring-only patients presented with moderate-severe/severe mitral regurgitation (vena contracta, 0.6 ± 0.1 cm; regurgitation volume, 52 ± 17 mL), with mainly a central jet and almost preserved ejection fraction (59% ± 6%). Cardiopulmonary bypass and crossclamp times were significantly shorter compared with controls (P < .0001). At follow-up (ring-only, 38 ± 36 months and controls, 36 ± 29 months), there were no late deaths in the ring-only group compared with 19 (4%) in the controls. Late follow-up revealed New York Heart Association functional class I or II in 95% of ring-only patients, compared with 90% of controls. Freedom from recurrent moderate or severe mitral regurgitation was 100% and 89% in the ring-only and control groups, respectively. Mitral annuloplasty for Barlow disease patients with multisegment involvement and mainly central regurgitant jet is both simple and reproducible with excellent late outcomes. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

[Role of serum leptin in the severity of coronary artery disease in patients with stable angina].

PubMed

Jerez-Valero, Miguel; Meliveo-García, Ana; Jordán-Martínez, Laura; Carrasco-Chinchilla, Fernando; Moreno-Santos, Inmaculada; Ordóñez, Antonio; Sánchez-Fernández, Pedro L; Vázquez, Rafael; Hernández-García, José M; Gómez-Doblas, Juan J; Pérez-Belmonte, Luis M; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel

2016-07-01

Leptin is a plasmatic peptide hormone that has been related to cardiovascular homeostasis and atherosclerosis but much is still unknown about its relationship with coronary artery disease. The aim of this study was to evaluate the value of serum leptin in patients with stable angina and its relationship with the severity of coronary disease. 204 patients, 152 with stable angina (coronary artery disease group) and 52 without coronary disease excluded by cardiac computerized tomography (control group) were included. The coronary artery disease group was divided into 2 subgroups according to severity of coronary disease (single or multivessel disease, 46 and 106 patients, respectively). Serum leptin levels were determined by Enzyme-Linked InmunoSorbent Assay. Leptin levels were significantly higher in patients with multivessel disease and were independently associated with a greater severity of coronary artery disease when compared with controls (OR 1.14; 95%CI: 1.03-1.27; p=0.014) and with patients with single vessel disease (OR 1.12; 95%CI: 1.01-1.25; p=0.036). Serum leptin was tested as a diagnostic marker of multivessel disease with an area under the curve obtained from Receiver Operating Characteristics of 0.6764 (95%CI 0.5765-0.7657). Serum leptin levels were associated in patients with stable angina with the severity of coronary artery disease, suggesting its value in the development of coronary disease and as a future therapeutic target. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Quality of life in children with Charcot-Marie-Tooth disease.

PubMed

Burns, Joshua; Ryan, Monique M; Ouvrier, Robert A

2010-03-01

The authors studied the health-related quality of life of children aged 5 to 18 years with Charcot-Marie-Tooth disease of varying types and severity and compared it with the general pediatric population. To capture and compare the quality-of-life data across a broad range of ages, the Child Health Questionnaire was completed by parents of 127 children with Charcot-Marie-Tooth disease. Affected children exhibited lower physical, psychological, and social well-being than the general pediatric population, with subsequent worsening of many domains with age. The type of Charcot-Marie-Tooth disease influenced some physical and behavioral quality-of-life domains, while gender, body size, and ethnicity did not. Parent characteristics had generally little impact on the reporting of their child's quality of life, although parents with Charcot-Marie-Tooth disease reported higher bodily pain in their children than those without. Overall, quality of life is negatively affected by the presence and severity of Charcot-Marie-Tooth disease in childhood.

Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey

PubMed Central

Johnson, Lorraine; Wilcox, Spencer; Mankoff, Jennifer

2014-01-01

Overview. The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. Methods. Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. Results. Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. Conclusions. CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this illness. PMID:24749006

Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

PubMed Central

Batool, Husniah; Nadeem, Ahmed; Tahir, Romeeza

2018-01-01

Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients). According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm), moderate (CAL 3-4 mm), and severe (CAL > 5 mm) forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease), a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization of CP. PMID:29670909

Bilateral versus unilateral thyroid eye disease

PubMed Central

Kashkouli, Mohsen Bahmani; Kaghazkanani, Reza; Heidari, Iraj; Ketabi, Nooshin; Jam, Sara; Azarnia, Shahrzad; Pakdel, Farzad

2011-01-01

Aims: The aim of this study was to compare demographics, clinical manifestations, associated systemic and ocular factors, severity and activity of patients with unilateral thyroid eye disease (U-TED) versus bilateral thyroid eye disease (B-TED). Materials and Methods: In a cross-sectional study, all patients with Graves’ hyperthyroidism and primary hypothyroidism seen in an endocrinology clinic were included from September 2003 to July 2006. Demographics, complete eye examination, severity score (NOSPECS, total eye score), and clinical activity score were recorded and compared in the B-TED and U-TED groups of patients. Results: From 851 patients with thyroid disorders, 303 (35.6%) had TED. Thirty-two patients (32/ 303, 10.56%) were found to have U-TED. Patients with U-TED (mean age 31.6 ± 11.6 years) were significantly younger than patients with B-TED (mean age 37.7 ± 14.7 years). Monovariate analysis (Chi-square and independent sample t-test) showed a significantly higher severity score in B-TED (U-TED 4.09±4.05, B-TED: 6.7±6.3; P= 0.002) and more activity score in B-TED (U-TED= 1.03±0.96, B-TED: 1.74±1.6, P= 0.001). However, multivariate analysis did not show any significant difference between the two groups in terms of age, gender, type of thyroid disease, duration of thyroid disease and TED, severity and activity of TED, smoking habit, and presentation of TED before or after the presentation of thyroid disease (0.1

Quantitative Susceptibility Mapping in Parkinson's Disease.

PubMed

Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.

PubMed

Vegter, S; Tolley, K; Wilson Waterworth, T; Jones, H; Jones, S; Jewell, D

2013-08-01

The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC. © 2013 John Wiley & Sons Ltd.

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality.

PubMed

Astrup, Elisabeth; Janardhanan, Jeshina; Otterdal, Kari; Ueland, Thor; Prakash, John A J; Lekva, Tove; Strand, Øystein A; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

2014-02-01

Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10-20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome. We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8. Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome.

Celiac Disease in Children with Severe Acute Malnutrition (SAM): A Hospital Based Study.

PubMed

Beniwal, Neetu; Ameta, Gaurav; Chahar, Chandra Kumar

2017-05-01

To evaluate the prevalence and clinical features of Celiac disease among children with severe acute malnutrition (SAM). This prospective observational study was conducted in PBM Children Hospital, Bikaner from July 2012 through December 2013. All consecutively admitted children with SAM were recruited. All subjects were screened for Celiac disease by serological test for IgA-anti tissue Transglutaminase (IgA tTG) antibodies. All seropositive children underwent upper gastrointestinal endoscopy for small bowel biopsy for the confirmation. Clinical features of patients with and without celiac disease were compared. The sero-prevalence (IgA tTg positivity) of Celiac disease was found to be 15.38% while prevalence of biopsy confirmed Celiac disease was 14.42% among SAM children. Abdominal distension, diarrhea, anorexia, constipation, pain in abdomen, vitamin deficiencies, edema, clubbing and mouth ulcers were more common in patients of Celiac disease compared to patients without Celiac disease but the difference was statistically significant only for abdominal distension and pain abdomen. There is a high prevalence of Celiac disease in SAM. Screening for Celiac disease (especially in presence of pain abdomen and abdominal distension) should be an essential part of work-up in all children with SAM.

Acute colonic diverticulitis: modern understanding of pathomechanisms, risk factors, disease burden and severity.

PubMed

Søreide, Kjetil; Boermeester, Marja A; Humes, David J; Velmahos, George C

2016-12-01

Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed. Literature search of risk factors, pathophysiology, epidemiology and disease burden/severity reported over the last decade. Acute diverticulitis is a common disease and has a high disease burden. Incidence of hospital admissions is reported around 71 per 100,000 population, with reported increase in several subpopulations over the last decades. The incidence is likely to increase further with the aging populations. Risk factors for left-sided acute diverticulitis include dietary, anthropometric and lifestyle factors. Disease mechanisms are still poorly understood, but a distinction between inflammation and infection is emerging. The integrative and complex role of the gut microbiota has become an interesting factor for both understanding the disease as well as a potential target for intervention using probiotics. Mild, self-limiting events are increasingly reported from studies of successful non-antibiotic management in a considerable number of cases. Risk markers of progression to or presence of severe, complicated disease are needed for better disease stratification. Current risk stratification by clinical, imaging or endoscopic means is imperfect and needs validation. Long-term results from minimal-invasive and comparative surgical trials may better help inform clinicians and patients. Over- and under-treatment as well as over- and under-diagnosis of severity is likely to continue in clinical practice due to lack of reliable, robust and universal severity and classification systems. Better understanding of pathophysiology is needed.

Differential expression of heat shock protein (HSP) 70-2 gene polymorphism in benign and malignant pancreatic disorders and its relationship with disease severity and complications.

PubMed

Srivastava, Puja; Shafiq, Nusrat; Bhasin, Deepak Kumar; Rana, Surinder Singh; Pandhi, Promila; Behera, Arunanshu; Kapoor, Rakesh; Malhotra, Samir; Gupta, Rajesh

2012-07-10

The role of heat shock protein (HSP) 70-2 gene polymorphism (at position 1267, A to G transition) in patients with pancreatic disorders is not clear. To evaluate HSP 70-2 gene polymorphism (at position 1267, A to G transition) in patients with acute and chronic pancreatitis as well as pancreatic carcinoma, and to find any association of this polymorphism with disease complications and severity. One-hundred and fifty patients (50 each of acute, chronic pancreatitis, and pancreatic carcinoma) and 50 healthy blood donors as controls were prospectively studied. Three alleles (AA, AG and GG) of HSP 70-2 gene determined by PstI restriction fragment length polymorphism. There was a statistically significant difference in the distribution pattern of HSP 70-2 gene polymorphism in patients with acute pancreatitis (P=0.001) and pancreatic carcinoma (P<0.001) as compared to controls. The frequency of mutant allele (G allele) was significantly higher in diseased group as compared to control group (19% in control group, 40% in acute pancreatitis, 33% in chronic pancreatitis and 45% in pancreatic carcinoma). No association of this polymorphism was found with disease severity in patients with acute and chronic pancreatitis or pancreatic carcinoma. In our patient sample the frequency of mutant allele (G allele) of HSP 70-2 gene is significantly higher in patients with acute pancreatitis and pancreatic carcinoma compared to controls (50 healthy blood donors). However, this polymorphism was not associated with disease severity and complications.

Fourteen-Genome Comparison Identifies DNA Markers for Severe-Disease-Associated Strains of Clostridium difficile▿†

PubMed Central

Forgetta, Vincenzo; Oughton, Matthew T.; Marquis, Pascale; Brukner, Ivan; Blanchette, Ruth; Haub, Kevin; Magrini, Vince; Mardis, Elaine R.; Gerding, Dale N.; Loo, Vivian G.; Miller, Mark A.; Mulvey, Michael R.; Rupnik, Maja; Dascal, Andre; Dewar, Ken

2011-01-01

Clostridium difficile is a common cause of infectious diarrhea in hospitalized patients. A severe and increased incidence of C. difficile infection (CDI) is associated predominantly with the NAP1 strain; however, the existence of other severe-disease-associated (SDA) strains and the extensive genetic diversity across C. difficile complicate reliable detection and diagnosis. Comparative genome analysis of 14 sequenced genomes, including those of a subset of NAP1 isolates, allowed the assessment of genetic diversity within and between strain types to identify DNA markers that are associated with severe disease. Comparative genome analysis of 14 isolates, including five publicly available strains, revealed that C. difficile has a core genome of 3.4 Mb, comprising ∼3,000 genes. Analysis of the core genome identified candidate DNA markers that were subsequently evaluated using a multistrain panel of 177 isolates, representing more than 50 pulsovars and 8 toxinotypes. A subset of 117 isolates from the panel had associated patient data that allowed assessment of an association between the DNA markers and severe CDI. We identified 20 candidate DNA markers for species-wide detection and 10,683 single nucleotide polymorphisms (SNPs) associated with the predominant SDA strain (NAP1). A species-wide detection candidate marker, the sspA gene, was found to be the same across 177 sequenced isolates and lacked significant similarity to those of other species. Candidate SNPs in genes CD1269 and CD1265 were found to associate more closely with disease severity than currently used diagnostic markers, as they were also present in the toxin A-negative and B-positive (A-B+) strain types. The genetic markers identified illustrate the potential of comparative genomics for the discovery of diagnostic DNA-based targets that are species specific or associated with multiple SDA strains. PMID:21508155

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children.

PubMed

Mazur, Natalie I; Bont, Louis; Cohen, Adam L; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A

2017-02-15

Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009-December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)-associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39-1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6-7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0-4.5; P = .05) compared with RSV monoinfection. RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

PubMed

Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

2017-11-01

The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

Dysphagia, malnutrition and gastrointestinal problems in patients with mitochondrial disease caused by the m3243A>G mutation.

PubMed

de Laat, P; Zweers, H E E; Knuijt, S; Smeitink, J A M; Wanten, G J A; Janssen, M C H

2015-01-01

Previous research has shown that dysphagia and gastrointestinal problems occur frequently in carriers of the m.3243A>G mutation; however, the exact frequency and severity have not been determined. We hypothesise that adult carriers have an increased risk for malnutrition. In this observational study we evaluated the presence of gastrointestinal problems and dysphagia in 92 carriers of the m.3243A>G mutation. The severity of the general disease involvement was classified using the Newcastle Mitochondrial Disease Adult Scale (NMDAS). Gastrointestinal involvement, dysphagia and the risk for malnutrition were scored using the Gastrointestinal Symptoms Questionnaire and the Malnutrition Universal Screening Tool. Gastrointestinal symptoms and anthropometrics were compared with healthy controls. Our results show that the height, weight and body mass index (BMI) of these carriers were lower than the national average (p < 0.05). Seventy-nine carriers (86%) suffered from at least one gastrointestinal symptom, mainly flatulence or hard stools. Both frequency and severity of symptoms were significantly increased compared with reference data of healthy Dutch adults. Of the carriers, 45% reported (mostly mild) dysphagia. Solid foods cause more problems than liquids. A negative correlation between BMI and heteroplasmy levels in urinary epithelial cells (UEC) was present (Spearman correlation coefficient = - 0.319, p = 0.003). Dysphagia and gastrointestinal problems, especially constipation, are common symptoms in the total m.3243A>G carriers cohort and are not related to heteroplasmy levels in UEC or disease severity. The severity of gastrointestinal problems as well as overall disease severity is associated with an increased risk for malnutrition.

Predictors of Outcome in Ulcerative Colitis.

PubMed

Waterman, Matti; Knight, Jo; Dinani, Amreen; Xu, Wei; Stempak, Joanne M; Croitoru, Kenneth; Nguyen, Geoffrey C; Cohen, Zane; McLeod, Robin S; Greenberg, Gordon R; Steinhart, A Hillary; Silverberg, Mark S

2015-09-01

Approximately 80% of patients with ulcerative colitis (UC) have intermittently active disease and up to 20% will require a colectomy, but little data available on predictors of poor disease course. The aim of this study was to identify clinical and genetic markers that can predict prognosis. Medical records of patients with UC with ≥5 years of follow-up and available DNA and serum were retrospectively assessed. Immunochip was used to genotype loci associated with immune mediated inflammatory disorders (IMIDs), inflammatory bowel diseases, and other single nucleotide polypmorphisms previously associated with disease severity. Serum levels of pANCA, ASCA, CBir1, and OmpC were also evaluated. Requirement for colectomy, medication, and hospitalization were used to group patients into 3 prognostic groups. Six hundred one patients with UC were classified as mild (n = 78), moderate (n = 273), or severe disease (n = 250). Proximal disease location frequencies at diagnosis were 13%, 21%, and 30% for mild, moderate, and severe UC, respectively (P = 0.001). Disease severity was associated with greater proximal extension rates on follow-up (P < 0.0001) and with shorter time to extension (P = 0.03) and to prednisone initiation (P = 0.0004). When comparing severe UC with mild and moderate UC together, diagnosis age >40 and proximal disease location were associated with severe UC (odds ratios = 1.94 and 2.12, respectively). None of the single nucleotide polypmorphisms or serum markers tested was associated with severe UC, proximal disease extension or colectomy. Older age and proximal disease location at diagnosis, but not genetic and serum markers, were associated with a more severe course. Further work is required to identify biomarkers that will predict outcomes in UC.

Comparative virulence and genomic analysis of 10 strains of Haemophilus parasuis

USDA-ARS?s Scientific Manuscript database

Haemophilus parasuis is the cause of Glasser's disease in swine, which is characterized by systemic infection resulting in polyserositis, meningitis, and arthritis. An enormous difference exists in the severity of disease caused by H. parasuis strains, ranging from lethal systemic disease to asympto...

Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility.

PubMed

Martin-Bastida, A; Lao-Kaim, N P; Loane, C; Politis, M; Roussakis, A A; Valle-Guzman, N; Kefalopoulou, Z; Paul-Visse, G; Widner, H; Xing, Y; Schwarz, S T; Auer, D P; Foltynie, T; Barker, R A; Piccini, P

2017-02-01

To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies. © 2016 EAN.

Cytokine profiling reveals decreased serum levels of CCL2 in active ocular toxoplasmosis.

PubMed

Rey, Amanda; Molins, Blanca; Llorenç, Victor; Pelegrín, Laura; Mesquida, Marina; Adán, Alfredo

2013-10-01

Toxoplasma gondii infection is an important cause of ocular disease. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immunocompetent individuals. The purpose of the current investigation was to study the cytokine profiles in serum from patients with ocular toxoplasmosis and to compare them with those obtained from healthy control subjects. Using a multiplex assay, we determined the serum concentration of granulocyte colony-stimulating factor (GCSF), interferon γ (IFNγ), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, chemokine (C-C motif) ligand 2 (CCL2) and tumour necrosis factor α (TNFα) in patients with inactive ocular toxoplasmosis (n=48), active ocular toxoplasmosis (n=21), and an age-matched and sex-matched healthy control group (n=25). In a subgroup of 17 patients with active disease, a second serum sample was obtained when the disease was inactive. Cytokine profiles were correlated with disease activity, severity and visual outcome. Levels of CCL2 were significantly reduced in patients with active ocular toxoplasmosis compared to the control group (564 ± 42 pg/mL vs 455 ± 35 pg/mL, p<0.05). Moreover, CCL2 levels were significantly lower during active ocular toxoplasmosis compared to inactive disease (569 ± 32 pg/mL vs 433 ± 32 pg/mL, p<0.01). GCSF and TNFα were elevated in patients with toxoplasmosis with poor visual outcome. No significant correlations were found with specific cytokine profiles and disease severity. Decreased serum levels of CCL2 may be associated with active ocular toxoplasmosis and could therefore serve as a marker of disease activity.

Dietary Fiber Intake Is Inversely Associated with Periodontal Disease among US Adults.

PubMed

Nielsen, Samara Joy; Trak-Fellermeier, Maria Angelica; Joshipura, Kaumudi; Dye, Bruce A

2016-12-01

Approximately 47% of adults in the United States have periodontal disease. Dietary guidelines recommend a diet providing adequate fiber. Healthier dietary habits, particularly an increased fiber intake, may contribute to periodontal disease prevention. Our objective was to evaluate the relation of dietary fiber intake and its sources with periodontal disease in the US adult population (≥30 y of age). Data from 6052 adults participating in NHANES 2009-2012 were used. Periodontal disease was defined (according to the CDC/American Academy of Periodontology) as severe, moderate, mild, and none. Intake was assessed by 24-h dietary recalls. The relation between periodontal disease and dietary fiber, whole-grain, and fruit and vegetable intakes were evaluated by using multivariate models, adjusting for sociodemographic characteristics and dentition status. In the multivariate logistic model, the lowest quartile of dietary fiber was associated with moderate-severe periodontitis (compared with mild-none) compared with the highest dietary fiber intake quartile (OR: 1.30; 95% CI: 1.00, 1.69). In the multivariate multinomial logistic model, intake in the lowest quartile of dietary fiber was associated with higher severity of periodontitis than dietary fiber intake in the highest quartile (OR: 1.27; 95% CI: 1.00, 1.62). In the adjusted logistic model, whole-grain intake was not associated with moderate-severe periodontitis. However, in the adjusted multinomial logistic model, adults consuming whole grains in the lowest quartile were more likely to have more severe periodontal disease than were adults consuming whole grains in the highest quartile (OR: 1.32; 95% CI: 1.08, 1.62). In fully adjusted logistic and multinomial logistic models, fruit and vegetable intake was not significantly associated with periodontitis. We found an inverse relation between dietary fiber intake and periodontal disease among US adults ≥30 y old. Periodontal disease was associated with low whole-grain intake but not with low fruit and vegetable intake. © 2016 American Society for Nutrition.

Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

PubMed

Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

2017-07-01

Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

Comparative studies of the genome, virulence, and protection of 10 Haemophilus parasuis strains

USDA-ARS?s Scientific Manuscript database

Haemophilus parasuis is the cause of Glässer’s disease in swine, which is characterized by systemic infection resulting in polyserositis, meningitis, and arthritis. An enormous difference exists in the severity of disease caused by H. parasuis strains, ranging from lethal systemic disease to asympto...

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

PubMed

Otterdal, Kari; Janardhanan, Jeshina; Astrup, Elisabeth; Ueland, Thor; Prakash, John A J; Lekva, Tove; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

2014-11-01

Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Cost effectiveness of memantine in Alzheimer's disease: an analysis based on a probabilistic Markov model from a UK perspective.

PubMed

Jones, Roy W; McCrone, Paul; Guilhaume, Chantal

2004-01-01

Clinical trials with memantine, an uncompetitive moderate-affinity NMDA antagonist, have shown improved clinical outcomes, increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer's disease. In a randomised double-blind, placebo-controlled, 28-week study conducted in the US, reductions in resource utilisation and total healthcare costs were noted with memantine relative to placebo. While these findings suggest that, compared with placebo, memantine provides cost savings, further analyses may help to quantify potential economic gains over a longer treatment period. To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer's disease over a 2-year period. A Markov model was constructed to simulate patient progression through a series of health states related to severity, dependency (determined by patient scores on the Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL] inventory and residential status ('institutionalisation') with a time horizon of 2 years (each 6-month Markov cycle was repeated four times). Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week, randomised, double-blind, placebo-controlled clinical trial. Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study, while data on quality-adjusted life-years (QALYs) were derived from a Danish longitudinal study. To ensure conservative estimates from the model, the base case analysis assumed drug effectiveness was limited to 12 months. Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model. Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters. Finally, a subgroup analysis was performed to determine which patients were most likely to benefit from memantine. Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective. The base case analysis found that, compared with no treatment, memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence, years in the community and QALYs. Sensitivity analyses supported these findings. For each category of Alzheimer's disease patient examined, treatment with memantine was a cost-effective strategy. The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of > or =10. This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment. These benefits appear to result from prolonged patient independence and delayed institutionalisation for moderately severe and severe Alzheimer's disease patients on memantine compared with no pharmacological treatment.

Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease.

PubMed

Sartini, Alessandro; Gitto, Stefano; Bianchini, Marcello; Verga, Maria Chiara; Di Girolamo, Maria; Bertani, Angela; Del Buono, Mariagrazia; Schepis, Filippo; Lei, Barbara; De Maria, Nicola; Villa, Erica

2018-01-24

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1, 95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4-110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

PubMed Central

Lewandowski, Laura B; Schanberg, Laura E; Thielman, Nathan; Phuti, Angel; Kalla, Asgar A; Okpechi, Ikechi; Nourse, Peter; Gajjar, Priya; Faller, Gail; Ambaram, Priya; Reuter, Helmuth; Spittal, Graeme; Scott, Christiaan

2016-01-01

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study reveals a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population. PMID:27488473

Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis.

PubMed

Mareedu, Neeharik; Schotthoefer, Anna M; Tompkins, Jason; Hall, Matthew C; Fritsche, Thomas R; Frost, Holly M

2017-10-01

Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis , which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection ( P < 0.01), require hospitalization ( P < 0.01), or receive prolonged courses of antimicrobials ( P < 0.01). Nausea or vomiting ( P < 0.01) and diarrhea ( P < 0.01) along with hyperbilirubinemia ( P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease.

PubMed

Lee, Jeong-Yoon; Kim, Ji Sun; Jang, Wooyoung; Park, Jinse; Oh, Eungseok; Youn, Jinyoung; Park, Suyeon; Cho, Jin Whan

2018-06-05

There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson's Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies. © 2018 S. Karger AG, Basel.

Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children

PubMed Central

Mazur, Natalie I.; Bont, Louis; Cohen, Adam L.; Cohen, Cheryl; von Gottberg, Anne; Groome, Michelle J.; Hellferscee, Orienka; Klipstein-Grobusch, Kerstin; Mekgoe, Omphile; Naby, Fathima; Moyes, Jocelyn; Tempia, Stefano; Treurnicht, Florette K.; Venter, Marietje; Walaza, Sibongile; Wolter, Nicole; Madhi, Shabir A.

2017-01-01

Background Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort. Methods Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009–December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death. Results Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)–associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39–1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6–7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0–4.5; P = .05) compared with RSV monoinfection. Conclusions RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study. PMID:27927871

Cardiovascular Disease in Patients with End-Stage Renal Disease on Hemodialysis

PubMed Central

Aoki, Jiro; Ikari, Yuji

2017-01-01

Cardiovascular disease is a major concern for patients with end-stage renal disease (ESRD), especially those on hemodialysis. ESRD patients with coronary artery disease often do not have symptoms or present with atypical symptoms. Coronary lesions in ESRD patients are characterized by increased media thickness, infiltration and activation of macrophages, and marked calcification. Several studies showed worsened clinical outcomes after coronary revascularization, which were dependent on the severity of renal dysfunction. ESRD patients on hemodialysis have the most severe renal dysfunction; thus, the clinical outcomes are worse in these patients than in those with other types of renal dysfunction. Medications for primary or secondary cardiovascular prevention are also insufficient in ESRD patients. Efficacy of drug-eluting stents is inferior in ESRD patients, compared to the excellent outcomes observed in patients with normal renal function. Unsatisfactory outcomes with trials targeting cardiovascular disease in patients with ESRD emphasize a large potential to improve outcomes. Thus, optimal strategies for diagnosis, prevention, and management of cardiovascular disease should be modified in ESRD patients. PMID:29515692

Health utility of patients with Crohn's disease and ulcerative colitis: a systematic review and meta-analysis.

PubMed

Malinowski, Krzysztof Piotr; Kawalec, Paweł

2016-08-01

The aim of this systematic review was to collect and summarize the current data on the utilities of patients with Crohn's disease (CD) and ulcerative colitis (UC). A meta-analysis of the obtained utilities was performed using a random-effects model and meta-regression by the disease type and severity. A bootstrap analysis was performed as it does not require assumption on distribution of the data. The highest utility among patients with CD and UC was observed when the diseases were in remission. The meta-regression analysis showed that both disease severity and an instrument/method/questionnaire used to obtain utilities were significant predictors of utility. Utility was the lowest for severe disease and the highest for disease in remission, the association was more notable in patients with CD compared with UC. Expert commentary: The issue of patients' utility is important for healthcare decision makers but it has not been fully investigated and requires further study.

Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

PubMed Central

Mohn, Kristin G.-I.; Cox, Rebecca Jane; Tunheim, Gro; Berdal, Jan Erik; Hauge, Anna Germundsson; Jul-Larsen, Åsne; Peters, Bjoern; Oftung, Fredrik

2015-01-01

Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza. PMID:26606759

The ethics of a proposed study of hematopoietic stem cell transplant for children with "less severe" sickle cell disease.

PubMed

Nickel, Robert S; Hendrickson, Jeanne E; Haight, Ann E

2014-08-07

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD. © 2014 by The American Society of Hematology.

Leptin levels in patients with systemic lupus erythematosus inversely correlate with regulatory T cell frequency.

PubMed

Wang, X; Qiao, Y; Yang, L; Song, S; Han, Y; Tian, Y; Ding, M; Jin, H; Shao, F; Liu, A

2017-11-01

Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.

Assessment of incidence of severe sepsis in Sweden using different ways of abstracting International Classification of Diseases codes: difficulties with methods and interpretation of results.

PubMed

Wilhelms, Susanne B; Huss, Fredrik R; Granath, Göran; Sjöberg, Folke

2010-06-01

To compare three International Classification of Diseases code abstraction strategies that have previously been reported to mirror severe sepsis by examining retrospective Swedish national data from 1987 to 2005 inclusive. Retrospective cohort study. Swedish hospital discharge database. All hospital admissions during the period 1987 to 2005 were extracted and these patients were screened for severe sepsis using the three International Classification of Diseases code abstraction strategies, which were adapted for the Swedish version of the International Classification of Diseases. Two code abstraction strategies included both International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, whereas one included International Classification of Diseases, Tenth Revision codes alone. None. The three International Classification of Diseases code abstraction strategies identified 37,990, 27,655, and 12,512 patients, respectively, with severe sepsis. The incidence increased over the years, reaching 0.35 per 1000, 0.43 per 1000, and 0.13 per 1000 inhabitants, respectively. During the International Classification of Diseases, Ninth Revision period, we found 17,096 unique patients and of these, only 2789 patients (16%) met two of the code abstraction strategy lists and 14,307 (84%) met one list. The International Classification of Diseases, Tenth Revision period included 46,979 unique patients, of whom 8% met the criteria of all three International Classification of Diseases code abstraction strategies, 7% met two, and 84% met one only. The three different International Classification of Diseases code abstraction strategies generated three almost separate cohorts of patients with severe sepsis. Thus, the International Classification of Diseases code abstraction strategies for recording severe sepsis in use today provides an unsatisfactory way of estimating the true incidence of severe sepsis. Further studies relating International Classification of Diseases code abstraction strategies to the American College of Chest Physicians/Society of Critical Care Medicine scores are needed.

[Determination of plasma EBV DNA in 91 children with EBV-associated diseases].

PubMed

Duan, Hong-Mei; Yao, Yao; Xie, Zheng-De; Yan, Jing; Hu, Ying-Hui; Yao, Yuan; Zhou, Ling; Shen, Kun-Ling

2009-11-01

To determine the plasma level of Epstein Barr virus (EBV) DNA in children with EBV associated diseases, and to investigate the dynamic changes of EBV DNA level after initial infection as well as the relationship between EBV DNA level and the diseases severity. The subjects consisted of 73 children with primary EBV infection (infectious mononucleosis, pneumonia,etc.) and 18 children with severe EBV-associated diseases (chronic active EBV infection, hemophagocytic lymphohistiocytosis, etc.). The plasma EBV DNA level was detected by a real-time PCR assay. The plasma EBV DNA level decreased with the infection time in children with primary EBV infection. Two weeks after infection, plasma EBV DNA was almost undetectable. The positive rate of plasma EBV DNA in children with severe EBV associated diseases increased significantly when compared with that in children with primary EBV infection (89% vs 16%; p<0.05). The level of EBV replication may be reduced with the infection time. Dynamic determination of blood EBV DNA is useful for the evaluation of disease severity in children with EBV infection.

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

PubMed Central

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-01-01

Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis.

PubMed

Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

2016-04-01

Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality.

Periodontal disease severity is associated with micronutrient intake.

PubMed

Luo, P-P; Xu, H-S; Chen, Y-W; Wu, S-P

2018-03-06

This study aimed to examine if specific micronutrients were associated with periodontal disease using data from the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Participants who were aged 30 years or more and received complete periodontal examinations were included. Regression analyses were performed to determine associations of variables of interest with periodontal disease. Data of 6415 NHANES participants were included in the analysis. Multivariable analysis revealed that less intake of vitamin A (adjusted odds ratio (aOR) = 1.784), vitamin B1 (aOR = 1.334), vitamin C (aOR = 1.401), vitamin E (aOR = 1.576), iron (aOR = 1.234), folate (aOR = 1.254) and phosphorus (aOR = 1.280) was associated with increased severity of periodontal disease. Compared with the highest level of vitamin D intake, the second highest level of vitamin D intake was associated with lower severity of periodontal disease (aOR = 0.727). Insufficient intake of vitamin A, B1, C and E, iron, folate and phosphorus was significantly associated with severity of periodontal disease. Results of the present study suggest that the above micronutrients may be increased in the diet or taken as dietary supplements in order to reduce severity of periodontal disease. © 2018 Australian Dental Association.

Retinal Disease Course in Usher Syndrome 1B Due to MYO7A Mutations

PubMed Central

Jacobson, Samuel G.; Cideciyan, Artur V.; Gibbs, Dan; Sumaroka, Alexander; Roman, Alejandro J.; Aleman, Tomas S.; Schwartz, Sharon B.; Olivares, Melani B.; Russell, Robert C.; Steinberg, Janet D.; Kenna, Margaret A.; Kimberling, William J.; Rehm, Heidi L.; Williams, David S.

2011-01-01

Purpose. To determine the disease course in Usher syndrome type IB (USH1B) caused by myosin 7A (MYO7A) gene mutations. Methods. USH1B patients (n = 33, ages 2–61) representing 25 different families were studied by ocular examination, kinetic and chromatic static perimetry, dark adaptometry, and optical coherence tomography (OCT). Consequences of the mutant alleles were predicted. Results. All MYO7A patients had severely abnormal ERGs, but kinetic fields revealed regional patterns of visual loss that suggested a disease sequence. Rod-mediated vision could be lost to different degrees in the first decades of life. Cone vision followed a more predictable and slower decline. Central vision ranged from normal to reduced in the first four decades of life and thereafter was severely abnormal. Dark adaptation kinetics was normal. Photoreceptor layer thickness in a wide region of central retina could differ dramatically between patients of comparable ages; and there were examples of severe losses in childhood as well as relative preservation in patients in the third decade of life. Comparisons were made between the mutant alleles in mild versus more severe phenotypes. Conclusions. A disease sequence in USH1B leads from generally full but impaired visual fields to residual small central islands. At most disease stages, there was preserved temporal peripheral field, a potential target for early phase clinical trials of gene therapy. From data comparing patients' rod disease in this cohort, the authors speculate that null MYO7A alleles could be associated with milder dysfunction and fewer photoreceptor structural losses at ages when other genotypes show more severe phenotypes. PMID:21873662

Retinal disease course in Usher syndrome 1B due to MYO7A mutations.

PubMed

Jacobson, Samuel G; Cideciyan, Artur V; Gibbs, Dan; Sumaroka, Alexander; Roman, Alejandro J; Aleman, Tomas S; Schwartz, Sharon B; Olivares, Melani B; Russell, Robert C; Steinberg, Janet D; Kenna, Margaret A; Kimberling, William J; Rehm, Heidi L; Williams, David S

2011-10-07

PURPOSE. To determine the disease course in Usher syndrome type IB (USH1B) caused by myosin 7A (MYO7A) gene mutations. METHODS. USH1B patients (n = 33, ages 2-61) representing 25 different families were studied by ocular examination, kinetic and chromatic static perimetry, dark adaptometry, and optical coherence tomography (OCT). Consequences of the mutant alleles were predicted. RESULTS. All MYO7A patients had severely abnormal ERGs, but kinetic fields revealed regional patterns of visual loss that suggested a disease sequence. Rod-mediated vision could be lost to different degrees in the first decades of life. Cone vision followed a more predictable and slower decline. Central vision ranged from normal to reduced in the first four decades of life and thereafter was severely abnormal. Dark adaptation kinetics was normal. Photoreceptor layer thickness in a wide region of central retina could differ dramatically between patients of comparable ages; and there were examples of severe losses in childhood as well as relative preservation in patients in the third decade of life. Comparisons were made between the mutant alleles in mild versus more severe phenotypes. CONCLUSIONS. A disease sequence in USH1B leads from generally full but impaired visual fields to residual small central islands. At most disease stages, there was preserved temporal peripheral field, a potential target for early phase clinical trials of gene therapy. From data comparing patients' rod disease in this cohort, the authors speculate that null MYO7A alleles could be associated with milder dysfunction and fewer photoreceptor structural losses at ages when other genotypes show more severe phenotypes.

Cytokine Network in Scrub Typhus: High Levels of Interleukin-8 Are Associated with Disease Severity and Mortality

PubMed Central

Astrup, Elisabeth; Janardhanan, Jeshina; Otterdal, Kari; Ueland, Thor; Prakash, John A. J.; Lekva, Tove; Strand, Øystein A.; Abraham, O. C.; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M.

2014-01-01

Background Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10–20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome. Methodology/Principal Findings We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8. Conclusions/Significance Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome. PMID:24516677

The ethyl acetate extract of alfalfa sprout ameliorates disease severity of autoimmune-prone MRL-lpr/lpr mice.

PubMed

Hong, Y H; Huang, C J; Wang, S C; Lin, B F

2009-03-01

Previous study showed that soy isoflavone supplement alleviates disease severity in autoimmune-prone mice. As the ethyl acetate extract of alfalfa sprout (AS) has selective oestrogenic and anti-inflammatory activity, this study evaluated the effects of alfalfa sprout ethyl acetate extract (ASEA) on disease severity of systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. In Experiment 1, five groups of 12-week-old female mice were per oral treated with vehicle (control), lyophilized AS (550 mg wt/kg BW), ASEA (ASEA, 25 mg/kg BW), coumestrol (CUM, 0.075 mg/kg BW) and tamoxifen (TAM, 0.375 mg/kg BW) as the positive control. The onset of proteinuria was delayed, and the life span was significantly longer in the ASEA and TAM groups but neither in the AS nor in the CUM groups, compared to the control. To examine the changes in the immunological parameters related to disease process, three more groups of MRL-lpr/lpr female mice (control, ASEA and TAM) were fed in a similar manner for 6 weeks in the Experiment 2. Flow cytometric analysis of splenocytes showed a significantly lower percentage of activated T cells in the ASEA and TAM groups. The ex-vivo interferon-gamma and interleukin (IL)-4 production from splenocytes and tumour necrosis factor-alpha and IL-1beta production from peritoneal exudate cells were also significantly lower in the ASEA group compared with the control. The ASEA group also had less severe glomerulonephritis. Thus, ASEA attenuated cytokine and inflammatory responses of self-reactive lymphocytes, decreased the disease severity, increased survival and life span of the autoimmune-prone MRL-lpr/lpr mice, suggesting a potential of ASEA in the treatment of autoimmune diseases.

A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

PubMed

Colpitts, Sara L; Kasper, Eli J; Keever, Abigail; Liljenberg, Caleb; Kirby, Trevor; Magori, Krisztian; Kasper, Lloyd H; Ochoa-Repáraz, Javier

2017-11-02

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.

Effect of essential oil of Origanum rotundifolium on some plant pathogenic bacteria, seed germination and plant growth of tomato

NASA Astrophysics Data System (ADS)

Dadaşoǧlu, Fatih; Kotan, Recep; Karagöz, Kenan; Dikbaş, Neslihan; Ćakmakçi, Ramazan; Ćakir, Ahmet; Kordali, Şaban; Özer, Hakan

2016-04-01

The aim of this study is to determine effect of Origanum rotundifolium's essential oil on some plant pathogenic bacterias, seed germination and plant growth of tomato. Xanthomonas axanopodis pv. vesicatoria strain (Xcv-761) and Clavibacter michiganensis ssp. michiganensis strain (Cmm) inoculated to tomato seed. The seeds were tested for germination in vitro and disease severity and some plant growth parameters in vivo. In vitro assay, maximum seed germination was observed at 62,5 µl/ml essential oil treatment in seeds inoculated with Xcv-761 and at 62,5 µl/ml essential oil and streptomycin treatment in seeds inoculated with Cmm. The least infected cotiledon number was observed at 500 µg/ml streptomycin treatment in seeds inoculated with Cmm. In vivo assay, maximum seed germination was observed at 250 µl/ml essential oil teratment in tomato inoculated with Cmm. Lowest disease severity, is seen in the CMM infected seeds with 250 µl/ml essential oil application these results were statistically significant when compared with pathogen infected seeds. Similarly, in application conducted with XCV-761 infected seed, the lowest disease severity was observed for seeds as a result of 250 µl/ml essential oil application. Also according to the results obtained from essential oil application of CMM infected seeds conducted with 62,5 µl/ml dose; while disease severity was found statistically insignificant compared to 250 µl/ml to essential oil application, ıt was found statistically significant compared to pathogen infected seeds. The results showed that essential oil of O. rotundifolium has a potential for some suppressed plant disease when it is used in appropriate dose.

Strategies for managing aortoiliac occlusions: access, treatment and outcomes

PubMed Central

Clair, Daniel G; Beach, Jocelyn M

2015-01-01

Treatment of severe aortoiliac disease has dramatically evolved from a dependence on open aortobifemoral grafting to hybrid and endovascular only approaches. Open surgery has been the gold standard treatment of severe aortoiliac disease with excellent patency rates, but with increased length of stay and major complications. In contrast, endovascular interventions can successfully treat almost any lesion with decreased risk, compared to open surgery. Although primary patency rates remain inferior, secondary endovascular interventions are often minor procedures resulting in comparable long-term outcomes. The risks of renal insufficiency, embolization and access complications are not insignificant; however, most can be prevented or managed without significant clinical consequence. Endovascular therapies should be considered a first-line treatment option for all patients with aortoiliac disease, especially those with high-risk cardiovascular comorbidities. PMID:25907618

Quality of Life and Gastrointestinal Symptoms in Long-Term Treated Dermatitis Herpetiformis Patients: A Cross-Sectional Study in Finland.

PubMed

Pasternack, Camilla; Kaukinen, Katri; Kurppa, Kalle; Mäki, Markku; Collin, Pekka; Reunala, Timo; Huhtala, Heini; Salmi, Teea

2015-12-01

Dermatitis herpetiformis (DH) is a cutaneous manifestation of celiac disease. Both conditions are treated with a restrictive life-long gluten-free diet (GFD). Treated celiac disease patients have been shown to have more severe gastrointestinal symptoms and inferior quality of life compared with healthy controls, but evidence regarding quality of life in DH is lacking. The aim was to evaluate whether long-term GFD-treated DH patients suffer from persistent gastrointestinal symptoms and if they experience a drawdown in quality of life. Gastrointestinal symptoms and quality of life were assessed in 78 long-term GFD-treated DH patients using the validated Gastrointestinal Symptom Rating Scale, Psychological General Well-Being and Short Form 36 Health Survey questionnaires. The findings were compared with 110 healthy controls, population-based reference values and 371 treated celiac disease controls. The median age of the DH patients at the time of the study was 57 years, and 51 % were male. Significant differences in gastrointestinal symptoms or quality of life were not detected when treated DH patients were compared with healthy controls, but treated DH patients had less severe gastrointestinal symptoms and increased quality of life compared with celiac disease controls. Female DH patients had more severe gastrointestinal symptoms and reduced vitality compared with male DH patients. The presence of skin symptoms and the adherence to or duration of GFD did not have any influence on gastrointestinal symptoms or quality of life. We conclude that long-term GFD-treated DH patients do not suffer from the burden of dietary treatment and have a quality of life comparable to that of controls.

[Severity assessment strategies based on administrative data using stroke as an example].

PubMed

Schubert, Ingrid; Hammer, Antje; Köster, Ingrid

2017-10-01

Information on disease severity is relevant for many studies with claims data in health service research, but only limited information is available in routine data. Stroke serves as an example to analyse whether the combination of different information in claims data can provide insight into the severity of a disease. As a first step, a literature search was conducted. Strategies to assess the severity of a disease by means of routine data were examined with regard to approval and applicability to German sickness fund data. In order to apply and extend the identified procedures, the statutory health insurance sample AOK Hessen/KV Hessen (VSH) served as data source. It is an 18.75 % random sample of persons insured by the AOK Hessen, with 2013 being the most recent year. Stroke patients were identified by the ICD-10 GM code I63 and I64. Patients with said diagnoses being coded as a hospital discharge diagnosis in 2012 were included due to an acute event in 2012 (n=944). The follow-up time was one year. Ten studies covering seven different methods to assess stroke severity were identified. Codes for coma (4.2 % of stroke patients in the SHI sample) as well as coma and/or the application of a PEG tube (9.8 % of the stroke patients) were applied as a proxy for disease severity of acute cases. Taking age, sex and comorbidity into consideration, patients in a coma show a significantly increased risk of mortality compared to those without coma. Three operationalisations were chosen as possible proxies for disease severity of stroke in the further course of disease: i) sequelae (hemiplegia, neurological neglect), ii) duration of the index inpatient stay, and iii) nursing care/ care level 3 for the first time after stroke. The latter proxy has the highest explanatory value for SHI costs. The studies identified use many variables mainly based on hospital information in order to describe disease severity. With the exception of coma, these proxies were neither validated nor did the authors provide more detailed grounds for their use. An identified score for stroke severity could not be applied to SHI data. To develop a comparable score requires a linkage of clinical and administrative data. Since routine data include information from all sectors of care, it should be explored whether these data (for example, the patients' care needs) are suitable to assess disease severity. For validation, separate databases and, optimally, primary patient data are necessary. Copyright © 2017. Published by Elsevier GmbH.

Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

PubMed

Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

2017-09-04

The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of local capillaries in GLs and TILs and the severity of kidney diseases.

Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behçet's disease.

PubMed

Alibaz-Oner, Fatma; Aldag, Belgin; Aldag, Mustafa; Unal, A Ugur; Mutiş, Aydan; Toptas, Tayfur; Ergun, Tulin; Direskeneli, Haner

2016-07-01

Deep venous thrombosis (DVT) is the most common form of vascular involvement in Behçet's disease (BD). Chronic post-thrombotic syndrome (PTS) develops in up to one-half of patients with DVT and is associated with impaired quality of life (QoL). There are no data on the severity of DVT-related PTS and its effect on QoL in patients with vascular BD (VBD). We aimed to evaluate PTS and venous disease-specific QoL in patients with VBD. This study included 50 patients (41 men, nine women) with VBD and 31 individuals matched for age and gender (22 men, nine women) with DVT associated with non-BD causes. The Villalta scale was used to assess PTS. The Venous Disability Score and the Venous Clinical Severity Score were used for the assessment of venous disease. Venous disease-specific QoL was measured through Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptom (VEINES-QoL/Sym) questionnaire. The Behçet Syndrome Activity Score (BSAS) questionnaire was used to assess disease activity. We observed a significantly lower risk of PTS together with significantly better VEINES-QoL/Sym, and Venous Disability Score in the VBD group compared with the non-BD group. When VBD patients with PTS were compared with patients without PTS, VEINES-QoL/Sym, and Venous Clinical Severity Score were significantly worse. BSAS was also significantly higher in patients with PTS. An inverse correlation was found between the VEINES-QoL and the BSAS in multivariate analysis. There were no differences between anticoagulant users and nonusers regarding the presence of PTS and scores of all of the venous assessment tools. We found lower PTS risk and better venous disease-specific QoL, symptom severity, and venous disability scores in VBD patients compared with the non-BD group. Venous disease-specific QoL negatively correlated with disease activity. Effective control of vascular inflammation through treatment in VBD might explain lower rates of PTS and better venous QoL outcomes in VBD patients. Our results suggest that successful control of BD activity might decrease the development of PTS, improve venous disease-specific QoL, and prevent relapses in VBD. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Correspondence and challenges as neurologists to Kumamoto Earthquakes in 2016.

PubMed

Nakajima, Makoto; Nakane, Nozomi; Takamatsu, Kotaro; Yamashita, Satoshi; Nakane, Shunya; Yamashita, Taro; Ando, Yukio

2016-12-28

Kumamoto Earthquakes in 2016 severely affected medical circumstances and condition of each patient with neuro-muscular diseases, in addition to having destroyed life circumstances of local residence. Number of neuro-muscular disease patients admitted to the Department of Neurology, Kumamoto University, the only university hospital in the prefecture, increased approximately twice compared to usual years. Most of the related facilities were able to admit emergency patients with neuro-muscular diseases although the hospital buildings were damaged in various degrees. A number of issues remained unsolved as to emergency contact system, securement of emergency beds for severe neuro-muscular diseases, and information system for these patients.

Association between major depressive disorder and odor identification impairment.

PubMed

Khil, Laura; Rahe, Corinna; Wellmann, Jürgen; Baune, Bernhard T; Wersching, Heike; Berger, Klaus

2016-10-01

There is evidence of olfactory deficits in patients with major depressive disorder (MDD) but causes and mechanisms are largely unknown. We compared 728 patients with current MDD and 555 non-depressed controls regarding odor identification impairment taking into account the severity of acute symptoms and of the disease course. We assessed current symptom severity with the Hamilton Depression Rating Scale, and disease course severity based on admission diagnosis (ICD-10, F32/F33) and self-reported hospitalization frequency, defined as infrequent (<2) and frequent (≥2) depression-related hospitalizations under constant disease duration. A score of <10 on the Sniffin' Sticks-Screen-12 test determined the presence of odor identification impairment. Compared to non-depressed controls patients with frequent (rapidly recurring) hospitalizations had an elevated chance of odor identification impairment, even after adjustment for smell-influencing factors, such as age and smoking, (OR=1.7; 95% CI 1.0-2.9). Patients with recurrent MDD (F33) also had an elevated odds of odor identification impairment compared to those with a first-time episode (F32, OR=1.5; 95% CI 1.0-2.4). In patients with a first-time episode the chance of odor identification impairment increased by 7% with each point increase in the Hamilton Score. Cross-sectional study. Variation in the use of psychotropic medication is a potential bias. Odor identification impairment was evident in MDD patients with first-time high symptom severity and in patients with a severe disease course. Whether odor identification impairment is a marker or mediator of structural and functional brain changes associated with acute or active MDD requires further investigations in longitudinal studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of Baseline Disease Severity Over 26 and 52 Weeks of Treatment with Calcitriol Ointment 3µg/g in Patients with Mild-to-moderate Plaque Psoriasis.

PubMed

Lebwohl, Mark; Preston, Norman; Gottschalk, Ronald W

2012-02-01

Calcitriol 3µg/g ointment has been shown to be a safe and effective treatment for adults with mild-to-moderate plaque psoriasis. This analysis evaluated the response to calcitriol 3µg/g ointment relative to baseline disease. Retrospective analysis of data from a 12-month safety and tolerability trial. At baseline, 40.1 percent (130/324) of patients had an affected body surface area of 11 to 20 percent, and 55.2 percent (179/324) had moderate and 25.9 percent (84/324) had severe disease according to global severity score. Patients applied calcitriol 3µg/g ointment twice daily for up to 52 weeks. Change in investigator's global severity scores and involved body surface area at Week 26 (N=249) and Week 52 (N=130) relative to baseline. Compared with baseline, most patients experienced at least a 1-grade improvement in global severity score at Weeks 26 (195/249, 78.3%) and 52 (109/130, 83.8%). Stabilization (i.e., no change in global severity score) was reported in 19.3 percent (48/249) at Week 26 and in 12.3 percent (16/130) at Week 52. Most patients also experienced at least a 1-grade improvement in body surface area involved at Weeks 26 (152/249, 61.0%) and 52 (95/130, 73.1%). Stabilization (no change in affected body surface area) was reported in 32.5 percent (81/249) at Week 26 and 24.6 percent (32/130) at Week 52. The proportion of patients experiencing improvement in global severity score and body surface area was comparable across all categories of severity and disease extent at baseline. This analysis suggests that calcitriol 3µg/g ointment use for 26 weeks (N=249) and 52 weeks (N=130) was associated with disease improvement or stabilization in most patients with plaque psoriasis.

High incidence of zinc deficiency among Filipino children with compensated and decompensated liver disease.

PubMed

Umusig-Quitain, Perlina; Gregorio, Germana V

2010-02-01

The role of zinc in the nutrition and growth of children with chronic liver disease is poorly defined. The present study determined the serum zinc levels of children with compensated liver disease (CLD) and decompensated liver disease (DLD) and compared this with healthy children. Zinc levels were also correlated with the severity of liver disease as measured by Child-Pugh scores. The study comprised of 60 children 0-10 years of age with chronic liver disease, defined as CLD (n = 30) if the Child-Pugh score was < 6, and DLD (n = 30) if the Child-Pugh score was > or = 6. Thirty healthy children 0-10 years served as controls. Serum zinc levels were measured by atomic absorption spectrometry. The 90 patients included 30 with CLD (mean age: 4.54 years: 21 boys; mean Child-Pugh score: 5.83), 30 with DLD (mean age: 1.39 years; 17 boys; mean Child-Pugh score: 9.53) and 30 healthy children (mean age: 4.6; 16 boys). Zinc levels of patients with CLD were significantly lower compared with the healthy controls (Mean [standard deviation]: 68.07 [31.55]vs 89.9 [25.9]microg/dL, P = 0.000), but significantly higher compared to the patients with DLD (48.8 [26.8]microg/dL). Correlation studies showed that the higher the Child-Pugh score, the lower the zinc levels (r = -0.460) Children with chronic liver disease, whether in a compensated or decompensated state, had lower serum zinc levels compared with the healthy controls. As the severity of liver disease worsened, the zinc levels decreased. The study suggests that zinc supplementation should constitute part of the micronutrient intake of children with chronic liver disease.

Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease.

PubMed

Albagha, Omar M E; Visconti, Micaela Rios; Alonso, Nerea; Wani, Sachin; Goodman, Kirsteen; Fraser, William D; Gennari, Luigi; Merlotti, Daniela; Gianfrancesco, Fernando; Esposito, Teresa; Rendina, Domenico; di Stefano, Marco; Isaia, Giancarlo; Brandi, Maria Luisa; Giusti, Francesca; Del Pino-Montes, Javier; Corral-Gudino, Luis; Gonzalez-Sarmiento, Rogelio; Ward, Lynley; Rea, Sarah L; Ratajczak, Thomas; Walsh, John P; Ralston, Stuart H

2013-11-01

Paget's disease of bone (PDB) has a strong genetic component. Here, we investigated possible associations between genetic variants that predispose to PDB and disease severity. Allelic variants identified as predictors of PDB from genome-wide association studies were analyzed in 1940 PDB patients from the United Kingdom, Italy, Western Australia, and Spain. A cumulative risk allele score was constructed by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations. In SQSTM1-negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score, which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM-positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium, and high levels of severity with a specificity of 70% and sensitivity of 55%. Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention. © 2013 American Society for Bone and Mineral Research.

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL 4.0 Generic Core Scales.

PubMed

Varni, James W; Limbers, Christine A; Burwinkle, Tasha M

2007-07-16

Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data. The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals. Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences. The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL 4.0 Generic Core Scales. These findings with the PedsQL have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated.

Impaired health-related quality of life in children and adolescents with chronic conditions: a comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL™ 4.0 Generic Core Scales

PubMed Central

Varni, James W; Limbers, Christine A; Burwinkle, Tasha M

2007-01-01

Background Advances in biomedical science and technology have resulted in dramatic improvements in the healthcare of pediatric chronic conditions. With enhanced survival, health-related quality of life (HRQOL) issues have become more salient. The objectives of this study were to compare generic HRQOL across ten chronic disease clusters and 33 disease categories/severities from the perspectives of patients and parents. Comparisons were also benchmarked with healthy children data. Methods The analyses were based on over 2,500 pediatric patients from 10 physician-diagnosed disease clusters and 33 disease categories/severities and over 9,500 healthy children utilizing the PedsQL™ 4.0 Generic Core Scales. Patients were recruited from general pediatric clinics, subspecialty clinics, and hospitals. Results Pediatric patients with diabetes, gastrointestinal conditions, cardiac conditions, asthma, obesity, end stage renal disease, psychiatric disorders, cancer, rheumatologic conditions, and cerebral palsy self-reported progressively more impaired overall HRQOL than healthy children, respectively, with medium to large effect sizes. Patients with cerebral palsy self-reported the most impaired HRQOL, while patients with diabetes self-reported the best HRQOL. Parent proxy-reports generally paralleled patient self-report, with several notable differences. Conclusion The results demonstrate differential effects of pediatric chronic conditions on patient HRQOL across diseases clusters, categories, and severities utilizing the PedsQL™ 4.0 Generic Core Scales from the perspectives of pediatric patients and parents. The data contained within this study represents a larger and more diverse population of pediatric patients with chronic conditions than previously reported in the extant literature. The findings contribute important information on the differential effects of pediatric chronic conditions on generic HRQOL from the perspectives of children and parents utilizing the PedsQL™ 4.0 Generic Core Scales. These findings with the PedsQL™ have clinical implications for the healthcare services provided for children with chronic health conditions. Given the degree of reported impairment based on PedsQL™ scores across different pediatric chronic conditions, the need for more efficacious targeted treatments for those pediatric patients with more severely impaired HRQOL is clearly and urgently indicated. PMID:17634123

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology].

PubMed

Novacek, G; Haas, T; Knoflach, P; Petritsch, W; Tilg, H; Vogelsang, H; Reinisch, W

2013-09-01

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications. © Georg Thieme Verlag KG Stuttgart · New York.

Genetic burden associated with varying degrees of disease severity in endometriosis

PubMed Central

Sapkota, Yadav; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; Rahmioglu, Nilufer; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Scott, Rodney J.; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.

2015-01-01

Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities. PMID:25882541

Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries.

PubMed

Sabre, Liis; Westerberg, Elisabet; Liik, Maarika; Punga, Anna R

2017-04-01

Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden. This cross-sectional study included southern counties in Sweden and Estonia of comparable size. All patients with a confirmed MG diagnosis were asked to answer two questionnaires including demographic and disease-specific data, lifestyle issues, and mental fatigue (Fatigue Severity Scale [FSS]). Clinical fatigue was assessed objectively through the Quantitative Myasthenia Gravis Score (QMG). Thirty-six of 92 identified patients in Estonia and 40 of 70 identified MG patients in Sweden chose to participate in the study. The demographic characteristics and symptoms reported by the patients were similar. QMG score did not differ; however, the Estonian patients scored their current subjective disease severity significantly higher (5.6 ± 2.8) compared to the Swedish patients (3.4 ± 2.3, p  = .0005). Estonian patients also had significantly higher FSS scores (5.0 ± 1.7) than Swedish patients (3.5 ± 1.6; p  = .001). Swedish patients were more active and performed physical activity more regularly (29.1% in Estonia and 74.2% in Sweden, p  = .004). Although, the patients had comparable clinical fatigue, Estonian patients evaluated their health state as being more severe and reported more mental fatigue than Swedish patients. These data indicate large regional differences in disease perception of MG, which is important to consider in international studies.

Using image analysis for quantitative assessment of needle bladder rust disease of Norway spruce.

PubMed

Ganthaler, A; Losso, A; Mayr, S

2018-06-01

High elevation spruce forests of the European Alps are frequently infected by the needle rust Chrysomyxa rhododendri , a pathogen causing remarkable defoliation, reduced tree growth and limited rejuvenation. Exact quantification of the disease severity on different spatial scales is crucial for monitoring, management and resistance breeding activities. Based on the distinct yellow discolouration of attacked needles, it was investigated whether image analysis of digital photographs can be used to quantify disease severity and to improve phenotyping compared to conventional assessment in terms of time, effort and application range. The developed protocol for preprocessing and analysis of digital RGB images enabled identification of disease symptoms and healthy needle areas on images obtained in ground surveys (total number of analysed images n  =   62) and by the use of a semiprofessional quadcopter ( n  =   13). Obtained disease severities correlated linearly with results obtained by manual counting of healthy and diseased needles for all approaches, including images of individual branches with natural background ( R 2  = 0.87) and with black background ( R 2  = 0.95), juvenile plants ( R 2  = 0.94), and top views and side views of entire tree crowns of adult trees ( R 2  = 0.98 and 0.88, respectively). Results underline that a well-defined signal related to needle bladder rust symptoms of Norway spruce can be extracted from images recorded by standard digital cameras and using drones. The presented protocol enables precise and time-efficient quantification of disease symptoms caused by C. rhododendri and provides several advantages compared to conventional assessment by manual counting or visual estimations.

Heritability of Lung Disease Severity in Cystic Fibrosis

PubMed Central

Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

2007-01-01

Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

Improved Correction of Misclassification Bias With Bootstrap Imputation.

PubMed

van Walraven, Carl

2018-07-01

Diagnostic codes used in administrative database research can create bias due to misclassification. Quantitative bias analysis (QBA) can correct for this bias, requires only code sensitivity and specificity, but may return invalid results. Bootstrap imputation (BI) can also address misclassification bias but traditionally requires multivariate models to accurately estimate disease probability. This study compared misclassification bias correction using QBA and BI. Serum creatinine measures were used to determine severe renal failure status in 100,000 hospitalized patients. Prevalence of severe renal failure in 86 patient strata and its association with 43 covariates was determined and compared with results in which renal failure status was determined using diagnostic codes (sensitivity 71.3%, specificity 96.2%). Differences in results (misclassification bias) were then corrected with QBA or BI (using progressively more complex methods to estimate disease probability). In total, 7.4% of patients had severe renal failure. Imputing disease status with diagnostic codes exaggerated prevalence estimates [median relative change (range), 16.6% (0.8%-74.5%)] and its association with covariates [median (range) exponentiated absolute parameter estimate difference, 1.16 (1.01-2.04)]. QBA produced invalid results 9.3% of the time and increased bias in estimates of both disease prevalence and covariate associations. BI decreased misclassification bias with increasingly accurate disease probability estimates. QBA can produce invalid results and increase misclassification bias. BI avoids invalid results and can importantly decrease misclassification bias when accurate disease probability estimates are used.

[Comparison Study of Oropharyngeal Microbiota in Case of Bronchial Asthma and Chronic Obstructive Pulmonary Disease in Different Severity Levels].

PubMed

Ogorodova, L M; Fedosenko, S V; Popenko, A S; Petrov, V A; Tyakht, A V; Saltykova, I V; Deev, I A; Kulikov, E S; Kirillova, N A; Govorun, V M; Kostryukova, E S

2015-01-01

The result of comparative study of oropharyngeal microbiota taxonomic composition in patients with different severity level of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is presented in this paper. To compare oropharyngeal microbiota composition in case of bronchial asthma and chronic obstructive pulmonary disease in different severity levels. 138 patients, 50 with BA and 88 with COPD were studied. For each patient was collected anamnesis vitae, swab from the back of the throat and performed physical examination. High-throughput 16S ribosomal RNA gene sequencing and bioinformatic analysis was employed to characterize the microbial communities. As a result of the study wasfound a number of differences on various taxonomic levels in microbiota's composition within group of patients with different severity level of BA and group of patients with different severity level of COPD and between those groups. COPD patients with GOLD 1-2 in comparison with GOLD 3-4 patiens are marked by prevalence of species Brevibacterium aureum, genus Scardovia, Coprococcus, Haemophilus, Moryella, Dialister, Paludibacter and decrease of Prevotella melaninogenica species. BA patients with severe uncontrolled asthma in comparison with patients which have mild persistent asthma are marked by decrease of Prevotella and increase of species Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis and genus Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas, Sneathia. Patient's microbiota in BA group in comparison with COPD group is characterized by the prevalence of Prevotella melaninogenica and genus Selenomonas, Granulicatella u Gemella, and decrease of Prevotella nigrescens, Haemophilus influenza and genus Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus u Sediminibacterium. There are no differences between microbiota composition in case of severe uncontrolled BA and very severe COPD. Lack of differences in oropharyngeal microbiota taxonomic composition between patients with severe uncontrolled BA and very severe COPD allow us to suggest a similarity of bronchopulmonary system condition in case of diseases' severe stages.

Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study

PubMed Central

Søgaard, Mette; Skjøth, Flemming; Kjældgaard, Jette Nordstrøm; Larsen, Torben Bjerregaard; Hjortshøj, Søren Pihlkjær; Riahi, Sam

2017-01-01

Objectives Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders. Design Nationwide registry-based cohort study. Setting Denmark (population 5.6 million), 2000–2015. Participants Patients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders. Exposure Inpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease. Primary and secondary outcome measures HRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT). Results Compared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15). Conclusion Patients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders. PMID:29217725

Ferritin levels predict severe dengue.

PubMed

Soundravally, R; Agieshkumar, B; Daisy, M; Sherin, J; Cleetus, C C

2015-02-01

Currently, no tests are available to monitor and predict severity and outcome of dengue. To find potential markers that predict dengue severity, the present study validated the serum level of three acute-phase proteins α-1 antitrypsin, ceruloplasmin and ferritin in a pool of severe dengue cases compared to non-severe forms and other febrile illness controls. A total of 96 patients were divided into two equal groups with group 'A' comprising dengue-infected cases and group 'B' with other febrile illness cases negative for dengue. Out of 48 dengue-infected cases, 13 had severe dengue and the remaining 35 were classified as non-severe dengue. Immunoassays were performed to evaluate the serum levels of acute-phase proteins both on the day of admission and on the day of defervescence. The efficiency of individual proteins in predicting the disease severity was assessed using receiver operating characteristic curve. The study did not find any significant difference in the levels of α-1 antitrypsin between the clinical groups. A significant increase in the levels of ceruloplasmin around defervescence in severe cases compared to non-severe and other febrile controls was observed and this is the first report describing the potential association of ceruloplasmin and dengue severity. Interestingly, a steady increase in the level of serum ferritin was recorded throughout the course of illness. Among all the three proteins, the elevated ferritin level could predict the disease severity with highest sensitivity and specificity of 76.9 and 83.3 %, respectively, on the day of admission and the same was found to be 90 and 91.6 % around defervescence. On the basis of this diagnostic efficiency, we propose that ferritin may serve as a potential biomarker for an early prediction of disease severity.

Diverting Ileostomy for the Treatment of Severe, Refractory, Pediatric Inflammatory Bowel Disease.

PubMed

Maxwell, Elizabeth C; Dawany, Noor; Baldassano, Robert N; Mamula, Petar; Mattei, Peter; Albenberg, Lindsey; Kelsen, Judith R

2017-09-01

Diverting ileostomy is used as a temporizing therapy in patients with perianal Crohn disease; however, little data exist regarding its use for colonic disease. The primary aim of the present study was to determine the role of diversion in severe refractory colonic inflammatory bowel disease (IBD) in a pediatric population. Retrospective study of patients who underwent diverting ileostomy at The Children's Hospital of Philadelphia from 2000 to 2014 for the management of severe, refractory colonic IBD. Clinical variables were compared in the 1 year before ileostomy and 1 year after diversion. Surgical and disease outcomes including changes in diagnosis were reviewed through 2015. Twenty-four patients underwent diverting ileostomy for refractory colonic disease. Initial diagnoses were Crohn disease in 10 (42%), ulcerative colitis in 1 (4%), and IBD-unclassified in 13 patients (54%). Comparing data before and after surgery, there were statistically significant improvements in height and weight velocities, height velocity z score, blood transfusion requirement, hemoglobin, and hospitalization rates. Chronic steroid use decreased from 71% to 22%. At the conclusion of the study, 10 patients had undergone subsequent colectomy, 7 had successful bowel reanastomosis, and 7 remain diverted. Seven patients (29%) had a change in diagnosis. There were 13 surgical complications in 7 subjects, including prolapse reduction, stoma revision, and resection of ischemic bowel. In pediatric patients with refractory colonic IBD, diverting ileostomy can be a successful intervention to induce clinical stability. Importantly, diversion is a steroid-sparing therapy and allows additional time to clarify the diagnosis.

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings.

PubMed

de Miguel-Díez, Javier; Carrasco-Garrido, Pilar; Rejas-Gutierrez, Javier; Martín-Centeno, Antonio; Gobartt-Vázquez, Elena; Hernandez-Barrera, Valentín; de Miguel, Angel Gil; Jimenez-Garcia, Rodrigo

2010-02-18

To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions. Epidemiologic, observational, and descriptive study (EPIDEPOC study). Patients > or = 40 years of age with stable COPD attending primary care settings were included. Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected. Results were compared between patients with or without associated heart disease. A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males. When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease. Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease. Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases. The annual total cost per patient was significantly higher in patients with heart disease; 2,937 +/- 2,957 vs. 1,749 +/- 2,120, p < 0.05. Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost. Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease.

Serum Uric Acid Levels and Uric Acid/Creatinine Ratios in Stable Chronic Obstructive Pulmonary Disease (COPD) Patients: Are These Parameters Efficient Predictors of Patients at Risk for Exacerbation and/or Severity of Disease?

PubMed

Durmus Kocak, Nagihan; Sasak, Gulsah; Aka Akturk, Ulku; Akgun, Metin; Boga, Sibel; Sengul, Aysun; Gungor, Sinem; Arinc, Sibel

2016-11-03

BACKGROUND Serum uric acid (sUA) levels were previously found to be correlated with hypoxic states. We aimed to determine the levels of sUA and sUA/creatinine ratios in stable COPD patients and to evaluate whether sUA level and sUA/creatinine ratio can be used as predictors of exacerbation risk and disease severity. MATERIAL AND METHODS This cross-sectional study included stable COPD patients and healthy controls. The sUA levels and sUA/creatinine ratios in each group were evaluated and their correlations with the study parameters were investigated. ROC analyses for exacerbation risk and disease severity were reported. RESULTS The study included 110 stable COPD patients and 52 healthy controls. The mean sUA levels and sUA/creatinine ratios were significantly higher in patients with COPD compared to healthy controls. The most common comorbidities in COPD patients were hypertension, diabetes, and coronary artery disease. While sUA levels were significantly higher in patients with hypertension (p=0.002) and malignancy (p=0.033), sUA/creatinine ratios was higher in patients with malignancy (p=0.004). The ROC analyses indicated that sUA/creatinine ratios can be more useful than sUA levels in predicting exacerbation risk (AUC, 0.586 vs. 0.426) and disease severity (AUC, 0.560 vs. 0.475) especially at higher cut-off values, but with low specificity. CONCLUSIONS Our study suggested that sUA levels and sUA/creatinine ratios increased in patients with stable COPD, especially among patients with certain comorbidities compared to healthy controls. At higher cut-off values, sUA levels and especially sUA/creatinine ratios, might be useful in predicting COPD exacerbation risk and disease severity. Also, their association with comorbidities, especially with malignancy and hypertension, may benefit from further investigation.

Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease.

PubMed

Ringman, John M; Sachs, Michael C; Zhou, Yan; Monsell, Sarah E; Saver, Jeffrey L; Vinters, Harry V

2014-07-01

Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited. To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD). We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE ε4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD. Prevalence of demographic characteristics and the APOE ε4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA. Persons with severe CAA compared with those without CAA were more likely to carry an APOE ε4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE ε4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7). Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in β-amyloid trafficking.

Periodontitis in Chronic Heart Failure.

PubMed

Fröhlich, Hanna; Herrmann, Kristina; Franke, Jennifer; Karimi, Alamara; Täger, Tobias; Cebola, Rita; Katus, Hugo A; Zugck, Christian; Frankenstein, Lutz

2016-08-01

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P <0.00001). The severity of periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases.

Warming and fertilization alter the dilution effect of host diversity on disease severity.

PubMed

Liu, Xiang; Lyu, Shengman; Zhou, Shurong; Bradshaw, Corey J A

2016-07-01

An essential ecosystem service is the dilution effect of biodiversity on disease severity, yet we do not fully understand how this relationship might change with continued climate warming and ecosystem degradation. We designed removal experiments in natural assemblages of Tibetan alpine meadow vegetation by manipulating plot-level plant diversity to investigate the relationship between different plant biodiversity indices and foliar fungal pathogen infection, and how artificial fertilization and warming affect this relationship. Although pathogen group diversity increased with host species richness, disease severity decreased as host diversity rose (dilution effect). The dilution effect of phylogenetic diversity on disease held across different levels of host species richness (and equal abundances), meaning that the effect arises mainly in association with enhanced diversity itself rather than from shifting abundances. However, the dilution effect was weakened by fertilization. Among indices, phylogenetic diversity was the most parsimonious predictor of infection severity. Experimental warming and fertilization shifted species richness to the most supported predictor. Compared to planting experiments where artificial communities are constructed from scratch, our removal experiment in natural communities more realistically demonstrate that increasing perturbation adjusts natural community resistance to disease severity. © 2016 by the Ecological Society of America.

Salivary and serum inflammatory mediators among pre-conception women with periodontal disease.

PubMed

Jiang, Hong; Zhang, Yiming; Xiong, Xu; Harville, Emily W; O, Karmin; Qian, Xu

2016-12-15

There have been inconsistent conclusions regarding the levels of inflammatory mediators in saliva and serum among people with or without periodontal disease. Although pre-conception has been put forward as the optimal time for the periodontal treatment in order to improving pregnancy outcomes, few studies have been conducted to examine inflammatory mediators in saliva and serum among pre-conception women. Pre-conception women were recruited between January 2012 and December 2014. Women were provided with an oral health examination to detect periodontal disease. Salivary and serum samples were collected at the same of examination. Inflammatory mediators includinginterleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α) and beta-glucuronidase (β-glucuronidase) were tested and analyzed among women with overall periodontal disease (n = 442) or moderate/severe periodontal disease (n = 247). Results were compared to that in women with a healthy periodontium (n = 91). Significantly increased concentrations of inflammatory mediators of IL-1β, IL-6, TNF-α and β-glucuronidase in saliva and IL-1β, β-glucuronidase and TNF-α in serum were found among pre-conception women with moderate/severe periodontal disease, compared with women without periodontal disease. Significantly increased levels were also found in all the above saliva inflammatory mediators and in serum IL-1β and TNF-α among women with overall periodontal disease. The levels of all inflammatory mediators in saliva and almost all inflammatory mediators except IL-6 in serum significantly increased with severity of periodontal disease. Periodontal disease is highly associated with the elevated levels of inflammatory mediators in saliva and some mediators in serum among pre-conception women.

Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease.

PubMed

Mehta, Seema; Lopez, Monica E; Chumpitazi, Bruno P; Mazziotti, Mark V; Brandt, Mary L; Fishman, Douglas S

2012-01-01

Our center previously reported its experience with pediatric gallbladder disease and cholecystectomies from 1980 to 1996. We aimed to determine the current clinical characteristics and risk factors for symptomatic pediatric gallbladder disease and cholecystectomies and compare these findings with our historical series. Retrospective, cross-sectional study of children, 0 to 18 years of age, who underwent a cholecystectomy from January 2005 to October 2008. We evaluated 404 patients: 73% girls; 39% Hispanic and 35% white. The mean age was 13.10 ± 0.91 years. The primary indications for surgery in patients 3 years or older were symptomatic cholelithiasis (53%), obstructive disease (28%), and biliary dyskinesia (16%). The median BMI percentile was 89%; 39% were classified as obese. Of the patients with nonhemolytic gallstone disease, 35% were obese and 18% were severely obese; BMI percentile was 99% or higher. Gallstone disease was associated with hemolytic disease in 23% (73/324) of patients and with obesity in 39% (126/324). Logistic regression demonstrated older age (P = .019) and Hispanic ethnicity (P < .0001) as independent risk factors for nonhemolytic gallstone disease. Compared with our historical series, children undergoing cholecystectomy are more likely to be Hispanic (P = .003) and severely obese (P < .0279). Obesity and Hispanic ethnicity are strongly correlated with symptomatic pediatric gallbladder disease. In comparison with our historical series, hemolytic disease is no longer the predominant risk factor for symptomatic gallstone disease in children.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

PubMed

Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

2017-07-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P <0.001) and chronic (20% versus 9%, P <0.001) graft- versus -host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P =0.76, respectively. Among recipients of unrelated donor transplants, acute graft- versus -host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P <0.001) but not chronic graft- versus -host disease (38% versus 32%, P =0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P =0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

Severity of Coexisting Patellofemoral Disease is Associated with Increased Impairments and Functional Limitations in Patients with Knee Osteoarthritis

PubMed Central

Farrokhi, Shawn; Piva, Sara R.; Gil, Alexandra B.; Oddis, Chester V.; Brooks, Maria M.; Fitzgerald, G. Kelley

2012-01-01

Objective To evaluate the association between severity of coexisting patellofemoral (PF) disease with lower limb impairments and functional limitations in patients with tibiofemoral (TF) osteoarthritis (OA). Methods Radiographic views of the TF and PF compartments, knee extension strength and knee range of motion were obtained for 167 patients with knee OA. Additionally, knee-specific symptoms and functional limitations were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Activities of Daily Living Scale (ADLS). Results “Moderate/Severe PFOA” was associated with lower knee extension strength (1.4±0.5 Nm/BW) compared to “No PFOA” (1.8±0.5 Nm/BW). Additionally, total knee range of motion was significantly lower for patients with “Moderate/Severe PFOA” (120.8°±14.4°) compared to “No PFOA” (133.5°±10.7°) and “Mild PFOA” (125.8°±13.0°). “Moderate/Severe PFOA” and “Mild PFOA” were also associated with less pain while standing (OR= 0.2; 95% CI: 0.1,0.7 and OR= 0.2; 95% CI: 0.1,0.6, respectively) on the WOMAC and “Moderate/Severe PFOA” was associated with greater difficulty with going downstairs (OR=2.9; 95% CI: 1.0,8.1) on the ADLS. Conclusion It appears that knees with more severe coexisting PF disease demonstrate features distinct from those observed in TFOA in isolation or in combination with mild PF disease. Treatment strategies targeting the PF joint may be warranted to mitigate the specific lower limb impairments and functional problems present in this patient population. PMID:23045243

Serum levels of matrix metalloproteinase-10 are associated with the severity of atherosclerosis in patients with chronic kidney disease.

PubMed

Coll, Blai; Rodríguez, Jose A; Craver, Lourdes; Orbe, Josune; Martínez-Alonso, Montserrat; Ortiz, Alberto; Díez, Javier; Beloqui, Oscar; Borras, Merce; Valdivielso, Jose M; Fernández, Elvira; Páramo, José A

2010-12-01

Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). As matrix metalloproteinases have a major role in atherosclerosis, we hypothesized that alterations in metalloproteinases-8, -10 and their tissue inhibitor-1 can be associated with the severity of atherosclerosis in patients with kidney disease. This was evaluated in a cross-sectional, observational study of 111 patients with stages I-V kidney disease, 217 patients on dialysis and 50 healthy controls. The severity of atherosclerosis was estimated with the atherosclerosis score (AS), combining the results of ankle-brachial index and carotid ultrasound. Serum levels of the two metalloproteinases and tissue inhibitor-1 were measured by enzyme-linked immunosorbent assay and were significantly increased in patients with kidney disease compared with the healthy controls, and higher in patients on dialysis than in earlier stages of CKD. The severity of the AS was also more prevalent in the dialysis group, in which serum levels of both metalloproteinases and tissue inhibitor-1 were significantly higher. After multivariate analysis, metalloproteinase-10, dialysis, C-reactive protein, age, and male gender were associated with increased risk of atherosclerosis. Thus, patients with CKD exhibit elevated levels of circulating metalloproteinase-10, and this was independently associated with the severity of atherosclerosis and may represent a new biomarker of atherosclerotic diseases.

Hyperthyroid vs hypothyroid eye disease: the same severity and activity

PubMed Central

Kashkouli, M B; Pakdel, F; Kiavash, V; Heidari, I; Heirati, A; Jam, S

2011-01-01

Purpose To compare demographics, severity, and activity of thyroid eye disease (TED) in patients with hyperthyroidism (Hr-TED) vs primary hypothyroidism (Ho-TED). Patients and Methods In a cross-sectional study, demographics, complete eye examination, severity score (NOSPECS, total hundred eye score), clinical activity score, and Rundle grading were recorded for patients with TED and different thyroid disorders referred from an endocrinology clinic from 2003 to 2006. Results TED was clinically found in 303 patients (303/851, 35.6%). The majority of them (280/303, 92.4%) had Graves' hyperthyroidism and 23 (23/303, 7.5%) had primary hypothyroidism. Mean age, gender, mean severity score, mean activity score, Rundle grade, unilateral presentation of TED, smoking habit, mean duration of eye disease, and mean interval time of thyroid to TED were not significantly different between the two groups (0.06

Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases

PubMed Central

Mori, Shunsuke; Hidaka, Michihiro; Kawakita, Toshiro; Hidaka, Toshihiko; Tsuda, Hiroyuki; Yoshitama, Tamami; Migita, Kiyoshi; Ueki, Yukitaka

2016-01-01

Objective Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity. Methods We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups. Results Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively). Conclusions Myelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia. PMID:27128679

Oxidants and anti-oxidants status in acne vulgaris patients with varying severity.

PubMed

Al-Shobaili, Hani A

2014-01-01

Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls. Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease's activity and to monitor its treatment.

The impact of a proactive chronic care management program on hospital admission rates in a German health insurance society.

PubMed

Hamar, Brent; Wells, Aaron; Gandy, William; Haaf, Andreas; Coberley, Carter; Pope, James E; Rula, Elizabeth Y

2010-12-01

Hospital admissions are the source of significant health care expenses, although a large proportion of these admissions can be avoided through proper management of chronic disease. In the present study, we evaluate the impact of a proactive chronic care management program for members of a German insurance society who suffer from chronic disease. Specifically, we tested the impact of nurse-delivered care calls on hospital admission rates. Study participants were insured individuals with coronary artery disease, heart failure, diabetes, or chronic obstructive pulmonary disease who consented to participate in the chronic care management program. Intervention (n  = 17,319) and Comparison (n  = 5668) groups were defined based on records of participating (or not participating) in telephonic interactions. Changes in admission rates were calculated from the year prior to (Base) and year after program commencement. Comparative analyses were adjusted for age, sex, region of residence, and disease severity (stratification of 3 [least severe] to 1 [most severe]). Overall, the admission rate in the Intervention group decreased by 6.2% compared with a 14.9% increase in the Comparison group (P  <  0.001). The overall decrease in admissions for the Intervention group was driven by risk stratification levels 2 and 1, for which admissions decreased by 8.2% and 14.2% compared to Comparison group increases of 12.1% and 7.9%, respectively. Additionally, Intervention group admissions decreased as the number of calls increased (P  =  0.004), indicating a dose-response relationship. These findings indicate that proactive chronic care management care calls can help reduce hospital admissions among German health insurance members with chronic disease.

AVX-470: A Novel Oral Anti-TNF Antibody with Therapeutic Potential in Inflammatory Bowel Disease

PubMed Central

Bhol, Kailash C.; Tracey, Daniel E.; Lemos, Brenda R.; Lyng, Gregory D.; Erlich, Emma C.; Keane, David M.; Quesenberry, Michael S.; Holdorf, Amy D.; Schlehuber, Lisa D.; Clark, Shawn A.; Fox, Barbara S.

2013-01-01

Background Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the GI tract that is currently treated with injected monoclonal antibodies specific for tumor necrosis factor (TNF). We developed and characterized AVX-470, a novel polyclonal antibody specific for human TNF. We evaluated the oral activity of AVX-470m, a surrogate antibody specific murine TNF, in several well-accepted mouse models of IBD. Methods AVX-470 and AVX-470m were isolated from the colostrum of dairy cows that had been immunized with TNF. The potency, specificity and affinity of both AVX-470 and AVX-470m were evaluated in vitro and compared with infliximab. AVX-470m was orally administered to mice either before or after induction of colitis and activity was measured by endoscopy, histopathology, immunohistochemistry and quantitative measurement of mRNA levels. Colitis was induced using either 2,4,6-trinitrobenzene sulfonate (TNBS) or dextran sodium sulfate (DSS). Results AVX-470 and AVX-470m were shown to be functionally comparable in vitro. Moreover, the specificity, neutralizing potency and affinity of AVX-470 were comparable to infliximab. Orally administered AVX-470m effectively reduced disease severity in several mouse models of IBD. Activity was comparable to that of oral prednisolone or parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited TNF-driven mucosal inflammation with minimal systemic exposure. Conclusions AVX-470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile comparable to that of infliximab. Oral administration of a surrogate antibody specific for mouse TNF is effective in treating mouse models of IBD, delivering the anti-TNF to the site of inflammation with minimal systemic exposure. PMID:23949620

Accuracy of ultrasonography in the detection of severe hepatic lipidosis in cats.

PubMed

Yeager, A E; Mohammed, H

1992-04-01

The accuracy of ultrasonography in detection of feline hepatic lipidosis was studied retrospectively. The following ultrasonographic criteria were associated positively with severe hepatic lipidosis: the liver hyperechoic, compared with falciform fat; the liver isoechoic or hyperechoic, compared with omental fat; poor visualization of intrahepatic vessel borders; and increased attenuation of sound by the liver. In a group of 36 cats with clinically apparent hepatobiliary disease and in which liver biopsy was done, liver hyperechoic, compared with falciform fat, was the best criterion for diagnosis of severe hepatic lipidosis with 91% sensitivity, 100% specificity, and 100% positive predictive value.

Revised Tubiana’s Staging System for Assessment of Disease Severity in Dupuytren’s Disease—Preliminary Clinical Findings

PubMed Central

Hindocha, Sandip; Stanley, John K.; Watson, James Stewart

2007-01-01

There are few objective staging systems to assess severity of Dupuytren’s disease (DD). Previous methods to assess severity of DD were based primarily on the degree of contracture of an affected digit measured using a goniometer. Nonetheless, this method of assessment alone may be incomplete, and other factors should be considered. White (n = 92) patients diagnosed with DD from northwest of England were assessed for DD. Objective criteria for evaluating severity incorporated quantified variables. The revised severity stage was correlated to a known staging system of DD (Tubiana’s staging system) which measures total flexion deformity for a single affected digit. Total revised severity staging scores ranged between 4 and 53 (mean = 18.7) and revealed significant positive correlation to Tubiana’s original staging system (r2 = 0.8, p < 0.001). There was significant difference between severity staging scores in those with a positive family history compared to those without (p < 0.01). In current practice, often, the degree of contracture in an affected digit is used solely as a measure of disease severity. Additional objective clinical information may provide useful prognostic indices for disease progression as well as postoperative outcome. PMID:18780081

Plus Disease in Retinopathy of Prematurity: Improving Diagnosis by Ranking Disease Severity and Using Quantitative Image Analysis.

PubMed

Kalpathy-Cramer, Jayashree; Campbell, J Peter; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D; Hutcheson, Kelly; Shapiro, Michael J; Repka, Michael X; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E; Chan, R V Paul; Chiang, Michael F

2016-11-01

To determine expert agreement on relative retinopathy of prematurity (ROP) disease severity and whether computer-based image analysis can model relative disease severity, and to propose consideration of a more continuous severity score for ROP. We developed 2 databases of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP (i-ROP) cohort study and recruited expert physician, nonexpert physician, and nonphysician graders to classify and perform pairwise comparisons on both databases. Six participating expert ROP clinician-scientists, each with a minimum of 10 years of clinical ROP experience and 5 ROP publications, and 5 image graders (3 physicians and 2 nonphysician graders) who analyzed images that were obtained during routine ROP screening in neonatal intensive care units. Images in both databases were ranked by average disease classification (classification ranking), by pairwise comparison using the Elo rating method (comparison ranking), and by correlation with the i-ROP computer-based image analysis system. Interexpert agreement (weighted κ statistic) compared with the correlation coefficient (CC) between experts on pairwise comparisons and correlation between expert rankings and computer-based image analysis modeling. There was variable interexpert agreement on diagnostic classification of disease (plus, preplus, or normal) among the 6 experts (mean weighted κ, 0.27; range, 0.06-0.63), but good correlation between experts on comparison ranking of disease severity (mean CC, 0.84; range, 0.74-0.93) on the set of 34 images. Comparison ranking provided a severity ranking that was in good agreement with ranking obtained by classification ranking (CC, 0.92). Comparison ranking on the larger dataset by both expert and nonexpert graders demonstrated good correlation (mean CC, 0.97; range, 0.95-0.98). The i-ROP system was able to model this continuous severity with good correlation (CC, 0.86). Experts diagnose plus disease on a continuum, with poor absolute agreement on classification but good relative agreement on disease severity. These results suggest that the use of pairwise rankings and a continuous severity score, such as that provided by the i-ROP system, may improve agreement on disease severity in the future. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study.

PubMed

Sada, Ken-Ei; Harigai, Masayoshi; Amano, Koichi; Atsumi, Tatsuya; Fujimoto, Shouichi; Yuzawa, Yukio; Takasaki, Yoshinari; Banno, Shogo; Sugihara, Takahiko; Kobayashi, Masaki; Usui, Joichi; Yamagata, Kunihiro; Homma, Sakae; Dobashi, Hiroaki; Tsuboi, Naotake; Ishizu, Akihiro; Sugiyama, Hitoshi; Okada, Yasunori; Arimura, Yoshihiro; Matsuo, Seiichi; Makino, Hirofumi

2016-09-01

To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated. According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had ≤1, 2, and ≥3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD-free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival. The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009.

Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

PubMed

Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2013-02-26

Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

Evaluation of Vitamin D Status in Newly Diagnosed Pemphigus Vulgaris Patients

PubMed Central

ZAREI, Mahnaz; JAVANBAKHT, Mohammad Hassan; CHAMS-DAVATCHI, Cheida; DANESHPAZHOOH, Maryam; ESHRAGHIAN, Mohammad Reza; DE-RAKHSHANIAN, Hoda; DJALALI, Mahmoud

2014-01-01

Abstract Background Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin or mucosa. Since low vitamin D status has been linked to many immune disorders, we designed this study to compare the vitamin D status in PV patients with healthy controls. Methods In this case-control study, vitamin D status of 32 newly diagnosed PV patients was compared with 36 healthy control subjects. All patients were selected from the specialized dermatology departments of Razi Hospital, Tehran University of Medical Sciences in a 2-year period (2009–2010). The severity of the disease was estimated according to Harman’s scores. Serum concentration of 25(OH)D was measured by Roche Elecsys System. Data were analyzed by independent t-test. Results Both groups were similar based on sex, age and body mass index. The mean duration of disease was 5.57±0.93 months. The mean oral and skin severities were 1.81±0.20 and 2.31±0.17 respectively, based on Harman’s scores. Serum 25(OH)D was significantly lower in PV patients compared to controls (-8.90; 95% CI, 2.29-15.51 and P = 0.009). There was a negative correlation between vitamin D level and the oral severity of disease (r = -0.39 and P = 0.02). Conclusion PV patients had significantly lower serum level of 25(OH)D compared to healthy subjects which might contribute to worsen the disease. These data indicate the importance of improving vitamin D level in pemphigus patients. PMID:26060722

Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.

PubMed

Nybacka, S; Öhman, L; Störsrud, S; Mybeck, M; Böhn, L; Wilpart, K; Winkvist, A; Bengtsson, U; Törnblom, H; Simrén, M

2018-06-01

Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P = .07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kU A /L, P < .001) and higher prevalence of self-reported food intolerance (28% vs 9%, P = .002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P = .028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity. © 2018 John Wiley & Sons Ltd.

Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

PubMed

Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto D; Olivas-Flores, Eva M; Garcia-Gonzalez, Araceli; Peguero-Gómez, Ana R; Flores-Navarro, Juan; Villa-Manzano, Alberto I; Zavaleta-Muñiz, Soraya A; Salazar-Paramo, Mario; Mejía, Mayra; Juárez-Contreras, Pablo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, Ernesto G; Trujillo-Hernández, Benjamin; Nava-Zavala, Arnulfo H; Gamez-Nava, Jorge I

2015-09-01

Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58μg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26μg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Differential proteomic analysis of virus-enriched fractions obtained from plasma pools of patients with dengue fever or severe dengue.

PubMed

Fragnoud, Romain; Flamand, Marie; Reynier, Frederic; Buchy, Philippe; Duong, Vasna; Pachot, Alexandre; Paranhos-Baccala, Glaucia; Bedin, Frederic

2015-11-14

Dengue is the most widespread mosquito-borne viral disease of public health concern. In some patients, endothelial cell and platelet dysfunction lead to life-threatening hemorrhagic dengue fever or dengue shock syndrome. Prognostication of disease severity is urgently required to improve patient management. The pathogenesis of severe dengue has not been fully elucidated, and the role of host proteins associated with viral particles has received little exploration. The proteomes of virion-enriched fractions purified from plasma pools of patients with dengue fever or severe dengue were compared. Virions were purified by ultracentrifugation combined with a water-insoluble polyelectrolyte-based technique. Following in-gel hydrolysis, peptides were analyzed by nano-liquid chromatography coupled to ion trap mass spectrometry and identified using data libraries. Both dengue fever and severe dengue viral-enriched fractions contained identifiable viral envelope proteins and host cellular proteins. Canonical pathway analysis revealed the identified host proteins are mainly involved in the coagulation cascade, complement pathway or acute phase response signaling pathway. Some host proteins were over- or under-represented in plasma from patients with severe dengue compared to patients with dengue fever. ELISAs were used to validate differential expression of a selection of identified host proteins in individual plasma samples of patients with dengue fever compared to patients with severe dengue. Among 22 host proteins tested, two could differentiate between dengue fever and severe dengue in two independent cohorts (olfactomedin-4: area under the curve (AUC), 0.958; and platelet factor-4: AUC, 0.836). A novel technique of virion-enrichment from plasma has allowed to identify two host proteins that have prognostic value for classifying patients with acute dengue who are more likely to develop a severe dengue. The impact of these host proteins on pathogenicity and disease outcome are discussed.

Costs of informal nursing care for patients with neurologic disorders: A systematic review.

PubMed

Diederich, Freya; König, Hans-Helmut; Mietzner, Claudia; Brettschneider, Christian

2018-01-02

To systematically review the economic burden of informal nursing care (INC), often called informal care, caused by multiple sclerosis (MS), Parkinson disease (PD), and epilepsy, with special attention to disease severity. We systematically searched MEDLINE, PsycINFO, and NHS Economic Evaluation Database for articles on the cost of illness of the diseases specified. Title, abstract, and full-text review were conducted in duplicate by 2 researchers. The distribution of hours and costs of INC were extracted and used to compare the relevance of INC across included diseases and disease severity. Seventy-one studies were included (44 on MS, 17 on PD, and 10 on epilepsy). Studies on epilepsy reported an average of 2.3-54.5 monthly hours of INC per patient. For PD, average values of 42.9-145.9 hours and for MS average values of 9.2-249 hours per patient per month were found. In line with utilized hours, costs of INC were lowest for epilepsy (interquartile range [IQR] 229-1,466 purchasing power parity US dollars [PPP-USD]) and similar for MS (IQR 4,454-11,222 PPP-USD) and PD (IQR 1,440-7,117 PPP-USD). In addition, costs of INC increased with disease severity and accounted for 38% of total health care costs in severe MS stages on average. The course of diseases and disease severity matter for the amount of INC used by patients. For each of the neurologic disorders, an increase in the costs of INC, due to increasing disease severity, considerably contributes to the rise in total health care costs. Copyright © 2017 American Academy of Neurology.

Impulsive-compulsive behaviors in parkin-associated Parkinson disease

PubMed Central

Fasano, Alfonso; Ginevrino, Monia; Petrucci, Simona; Ricciardi, Lucia; Bove, Francesco; Criscuolo, Chiara; Moccia, Marcello; De Rosa, Anna; Sorbera, Chiara; Bentivoglio, Anna Rita; Barone, Paolo; De Michele, Giuseppe; Pellecchia, Maria Teresa; Valente, Enza Maria

2016-01-01

Objective: The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation. Methods: We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale (QUIP-RS) was adopted to rate ICB severity. Results: Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score. Conclusions: Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity. PMID:27590295

Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases

PubMed Central

Arnold, Staci D.; Brazauskas, Ruta; He, Naya; Li, Yimei; Aplenc, Richard; Jin, Zhezhen; Hall, Matt; Atsuta, Yoshiko; Dalal, Jignesh; Hahn, Theresa; Khera, Nandita; Bonfim, Carmem; Majhail, Navneet S.; Diaz, Miguel Angel; Freytes, Cesar O.; Wood, William A.; Savani, Bipin N.; Kamble, Rammurti T.; Parsons, Susan; Ahmed, Ibrahim; Sullivan, Keith; Beattie, Sara; Dandoy, Christopher; Munker, Reinhold; Marino, Susana; Bitan, Menachem; Abdel-Azim, Hisham; Aljurf, Mahmoud; Olsson, Richard F.; Joshi, Sarita; Buchbinder, Dave; Eckrich, Michael J.; Hashmi, Shahrukh; Lazarus, Hillard; Marks, David I.; Steinberg, Amir; Saad, Ayman; Gergis, Usama; Krishnamurti, Lakshmanan; Abraham, Allistair; Rangarajan, Hemalatha G.; Walters, Mark; Lipscomb, Joseph; Saber, Wael; Satwani, Prakash

2017-01-01

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000–2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85–95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8–160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7–20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0–3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2–5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029–$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time. PMID:28818869

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A description of the severity and extent of disease using the Bollinger angiogram scoring method and the TransAtlantic Inter-Society Consensus II classification.

PubMed

Bradbury, Andrew W; Adam, Donald J; Bell, Jocelyn; Forbes, John F; Fowkes, F Gerry R; Gillespie, Ian; Ruckley, Charles Vaughan; Raab, Gillian M

2010-05-01

The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed in patients with severe lower limb ischemia (rest pain, tissue loss) who survive for 2 years after intervention that initial randomization to bypass surgery, compared with balloon angioplasty, was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months, respectively. The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic (angiographic) patterns of disease. Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus (TASC) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes. As was to be expected from the randomization process, patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II. In patients with the least overall disease, it tended to be concentrated in the superficial femoral and popliteal arteries, which were the commonest sites of disease overall. The below knee arteries became increasingly involved as the overall severity of disease increased, but the disease in the above knee arteries did not tend to worsen. The posterior tibial artery was the most diseased crural artery, whereas the peroneal appeared relatively spared. There was less interobserver disagreement with the Bollinger method than with the TASC II classification system, which also appears inherently less sensitive to clinically important differences in infrapopliteal disease among patients with severe leg ischemia. Anatomic (angiographic) disease description in patients with severe leg ischemia requires a reproducible scoring system that is sensitive to differences in crural artery disease. The Bollinger system appears well suited for this purpose, but the TASC II classification system less so. We hope this detailed analysis will facilitate appropriate generalization of the BASIL trial data to other groups of patients affected by similar anatomic (angiographic) patterns of disease. Crown Copyright (c) 2010. Published by Mosby, Inc. All rights reserved.

Self-Reported Fractures in Dermatitis Herpetiformis Compared to Coeliac Disease

PubMed Central

Pasternack, Camilla; Mansikka, Eriika; Kaukinen, Katri; Hervonen, Kaisa; Reunala, Timo; Collin, Pekka; Mattila, Ville M.

2018-01-01

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased bone fracture risk is known to associate with coeliac disease, but this has been only scantly studied in DH. In this study, self-reported fractures and fracture-associated factors in DH were investigated and compared to coeliac disease. Altogether, 222 DH patients and 129 coeliac disease-suffering controls were enrolled in this study. The Disease Related Questionnaire and the Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires were mailed to participants; 45 out of 222 (20%) DH patients and 35 out of 129 (27%) of the coeliac disease controls had experienced at least one fracture (p = 0.140). The cumulative lifetime fracture incidence did not differ between DH and coeliac disease patients, but the cumulative incidence of fractures after diagnosis was statistically significantly higher in females with coeliac disease compared to females with DH. The DH patients and the coeliac disease controls with fractures reported more severe reflux symptoms compared to those without, and they also more frequently used proton-pump inhibitor medication. To conclude, the self-reported lifetime bone fracture risk is equal for DH and coeliac disease. After diagnosis, females with coeliac disease have a higher fracture risk than females with DH. PMID:29538319

Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study.

PubMed

Bouwense, Stefan A W; Olesen, Søren S; Drewes, Asbjørn M; Frøkjær, Jens B; van Goor, Harry; Wilder-Smith, Oliver H G

2013-01-01

The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study. Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together. The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis.

The impact of fibromyalgia on health status according to the types, demographic background and pain index.

PubMed

Ghavidel-Parsa, Banafsheh; Bidari, Ali; Maafi, Alireza A; Hassankhani, Amir; Hajiabbasi, Asghar; Montazeri, Ali; Sanaei, Omid; Ghalehbaghi, Babak

2016-01-01

To compare fibromyalgia (FM) core symptoms, FM impact severity and health status between the recently defined type A and type B of fibromyalgia. To compare disease impact and health status between FM patients and non-FM chronic pain control group. Finally, to compare health related quality of life and disease symptom severity by demographic background and widespread pain index (WPI). A total of 284 consecutive FM patients and 96 non-FM control patients were enrolled. The information of four questionnaires including the Fibromyalgia Survey Questionnaire (FSQ), the Fibromyalgia Impact Questionnaire (FIQ), the 12-item Short Form Health Survey (SF-12) and questionnaires regarding demographic features were collected from a local FM registry. Of all FM patients, 102 (94%) and 7 (6%) were type A and B, respectively. We found statistically significant differences in symptomatology, the FIQ scores and the SF-12 subscales across two type and control groups (p<0.001). However, when we compared these scores pairwise, except WPI there were no significant differences in other scores between type A and B. Also, there were no significant differences in FIQ and SF-12 scores across different age or educational status groups. Interestingly, patients with higher WPI had significantly higher FIQ (overall, symptom, and total) scores, worse PCS-12 and MCS-12 scores, and vice versa. Type B constitutes a minor but important component of FM that probably has a marked impact on the patient's perceived illness severity and quality of life. Further, WPI probably is the most important single indicator of disease severity and quality of life in FM.

Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children.

PubMed

Newton, Kimberly P; Feldman, Haruna S; Chambers, Christina D; Wilson, Laura; Behling, Cynthia; Clark, Jeanne M; Molleston, Jean P; Chalasani, Naga; Sanyal, Arun J; Fishbein, Mark H; Lavine, Joel E; Schwimmer, Jeffrey B

2017-08-01

To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD. A multicenter, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weight was categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with the birth weight distribution in the general US population. The severity of liver histology was assessed by birth weight category. Children with NAFLD (n = 538) had overrepresentation of both LBW and HBW compared with the general US population (LBW, 9.3%; NBW, 75.8%; HBW, 14.9% vs LBW, 6.1%; NBW, 83.5%; HBW 10.5%; P < .0001). Children with HBW had significantly greater odds of having more severe steatosis (OR, 1.82, 95% CI. 1.15-2.88) and nonalcoholic steatohepatitis (OR, 2.03; 95% CI, 1.21-3.40) compared with children with NBW. In addition, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR, 2.23; 95% CI, 1.08-4.62). Birth weight involves maternal and in utero factors that may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Pretreatment chest x-ray severity and its relation to bacterial burden in smear positive pulmonary tuberculosis.

PubMed

Murthy, S E; Chatterjee, F; Crook, A; Dawson, R; Mendel, C; Murphy, M E; Murray, S R; Nunn, A J; Phillips, P P J; Singh, Kasha P; McHugh, T D; Gillespie, S H

2018-05-21

Chest radiographs are used for diagnosis and severity assessment in tuberculosis (TB). The extent of disease as determined by smear grade and cavitation as a binary measure can predict 2-month smear results, but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis. Pre-treatment chest x-rays from 1837 participants with smear-positive pulmonary TB enrolled into the REMoxTB trial (Gillespie et al., N Engl J Med 371:1577-87, 2014) were retrospectively reviewed. Two clinicians blinded to clinical details using the Ralph scoring system performed separate readings. An independent reader reviewed discrepant results for quality assessment and cavity presence. Cavitation presence was plotted against time to positivity (TTP) of sputum liquid cultures (MGIT 960). The Wilcoxon rank sum test was performed to calculate the difference in average TTP for these groups. The average lung field affected was compared to log 10 TTP by linear regression. Baseline markers of disease severity and patient characteristics were added in univariable regression analysis against radiological severity and a multivariable regression model was created to explore their relationship. For 1354 participants, the median TTP was 117 h (4.88 days), being 26 h longer (95% CI 16-30, p < 0.001) in patients without cavitation compared to those with cavitation. The median percentage of lung-field affected was 18.1% (IQR 11.3-28.8%). For every 10-fold increase in TTP, the area of lung field affected decreased by 11.4%. Multivariable models showed that serum albumin decreased significantly as the percentage of lung field area increased in both those with and without cavitation. In addition, BMI and logged TTP had a small but significant effect in those with cavitation and the number of severe TB symptoms in the non-cavitation group also had a small effect, whilst other factors found to be significant on univariable analysis lost this effect in the model. The radiological severity of disease on chest x-ray prior to treatment in smear positive pulmonary TB patients is weakly associated with the bacterial burden. When compared against other variables at diagnosis, this effect is lost in those without cavitation. Radiological severity does reflect the overall disease severity in smear positive pulmonary TB, but we suggest that clinicians should be cautious in over-interpreting the significance of radiological disease extent at diagnosis.

Neovascularization in Vertebral Artery Atheroma-A Dynamic Contrast-Enhanced Magnetic Resonance Imaging-Based Comparative Study in Patients with Symptomatic and Asymptomatic Carotid Artery Disease.

PubMed

Usman, Ammara; Yuan, Jianmin; Patterson, Andrew J; Graves, Martin J; Varty, Kevin; Sadat, Umar; Gillard, Jonathan H

2018-05-24

Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. K trans was calculated in the adventitia and plaque as a measure of neovessel permeability. Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial K trans and plaque K trans (.08 ± .01 min -1 , .07 ± .01 min -1 ) compared with Group 2 (.06 ± .01 min -1 , .06 ± .01 min -1 ) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Severe tophaceous gout and disability: changes in the past 15 years.

PubMed

López López, Carlos Omar; Lugo, Everardo Fuentes; Alvarez-Hernández, Everardo; Peláez-Ballestas, Ingris; Burgos-Vargas, Rubén; Vázquez-Mellado, Janitzia

2017-01-01

Epidemiologic data from recent decades show a significant increase in the prevalence and incidence of gout worldwide, in addition to changes in its clinical expression. Our objective was to compare the frequency of the severity of gout and disability in two patient groups at our clinic during different periods. We included and compared data of two groups: group A (1995-2000), patients from previous report, and group B (2010-2014), the baseline data of current patients participating in a cohort (GRESGO). This evaluation included data of socioeconomic and educational levels, demographics, associated diseases, previous treatment, clinical and biochemical data, and disability evaluated using the Health Assessment Questionnaire (HAQ). We included data of 564 gout patients. Participants were 35.7 ± 12.7 years old at onset and had 12.0 ± 9.2-years disease duration at their first evaluation in our department. Group B patients were younger, had higher educational and socioeconomic levels, and had more severe disease. However, this group had less frequency of some associated diseases and significantly higher HAQ scores. With increased HAQ score, a higher number of acute flares and tender, limited-to-motion, and swollen joints were seen. The spectrum of gout has changed over the past decade. A higher percentage of our patients had a severe form of disease, were younger, had earlier disease onset, and had more disability reflected in higher HAQ scores. In our current patient group, the variable most associated with disability was limited-to-motion joints; however, the number of acute flares and tender and swollen joints was also higher in patients with greater disability.

Clinical spectrum of Castleman disease-associated neuropathy.

PubMed

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

Evaluating Disease Severity in Chronic Pain Patients with and without Fibromyalgia: A Comparison of the Symptom Impact Questionnaire and the Polysymptomatic Distress Scale.

PubMed

Friend, Ronald; Bennett, Robert M

2015-12-01

To compare the relative effectiveness of the Polysymptomatic Distress Scale (PSD) with the Symptom Impact Questionnaire (SIQR), the disease-neutral revision of the updated Fibromyalgia Impact Questionnaire (FIQR), in their ability to assess disease activity in patients with rheumatic disorders both with and without fibromyalgia (FM). The study included 321 patients from 8 clinical practices with some 16 different chronic pain disorders. Disease severity was assessed by the Medical Outcomes Study Short Form-36 (SF-36). Univariate analyses were used to assess the magnitude of PSD and SIQR correlations with SF-36 subscales. Hierarchical stepwise regression was used to evaluate the unique contribution of the PSD and SIQR to the SF-36. Random forest regression probed the relative importance of the SIQR and PSD components as predictors of SF-36. The correlations with the SF-36 subscales were significantly higher for the SIQR (0.48 to 0.78) than the PSD (0.29 to 0.56; p < 0.001). Stepwise regression revealed that the SIQR was contributing additional unique variance on SF-36 subscales, which was not the case for the PSD. Random forest regression showed SIQR Function, Symptoms, and Global Impact subscales were more important predictors of SF-36 than the PSD. The single SIQR pain item contributed 55% of SF-36 pain variance compared to 23% with the 19-point WPI (the Widespread Pain Index component of PSD). The SIQR, the disease-neutral revision of the updated FIQ, has several important advantages over the PSD in the evaluation of disease severity in chronic pain disorders.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Dengue in the elderly: a review.

PubMed

Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

2017-08-01

Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

Comparison of Road Traffic Injury Characteristics between Local versus Floating Migrant Patients in a Tertiary Hospital between 2007 and 2010

PubMed Central

Xu, Chungui; Wang, Yanhua; Han, Na; Kou, Yuhui; Yin, Xiaofeng; Zhang, Peixun; Wang, Tianbing; Zhang, Dianying; Jiang, Baoguo

2014-01-01

Background The aim of this study is to give a description of the road traffic injuries (RTIs) characteristics of floating migrant population by comparing with those of local residents in a harbor city of China. Methods A population-based descriptive study was carried out between 2007 and 2010 with RTI patient records from the Fifth Center Hospital of Tianjin. Inpatient diagnoses of RTI patients were defined using the International Classification of Diseases, Tenth Revision (ICD-10) codes. We analyzed the demographics and general characteristics of RTI patients that were in the hospital during the four years. In order to compare the group differences between local resident patients and floating migrant patients, the distribution of their ages, diagnoses, severity of injuries, duration of inpatient stays, hospitalization cost were analyzed. Results People between the ages of 16 and 55 were the most likely to suffer RTIs. The floating migrant patients between the ages of 16 and 45 had a higher incidence of accidents, while local resident patients between 46 and 55 had a higher incidence of accidents. Compared to local resident patients, floating migrant patients were more vulnerable to open injuries and severe traffic injuries. With the severity of injuries ranked from mild to severe, floating migrant patients had lower duration of inpatient stay, but higher hospitalization costs compared to local resident patients. Conclusions Floating migrant patients had a different age distribution, severity of injuries, diseases, inpatient duration and hospitalization cost compared with local resident patients. Compared to local resident patients, floating migrants had a higher risk to RTIs and were more vulnerable to severer traffic accidents at lower ages. PMID:24475023

Proinflammatory chemokines are major mediators of exuberant immune response associated with Influenza A (H1N1) pdm09 virus infection.

PubMed

Thomas, Maria; Mani, Reeta Subramaniam; Philip, Mariamma; Adhikary, Ranjeeta; Joshi, Sangeeta; Revadi, Srigiri S; Buggi, Shashidhar; Desai, Anita; Vasanthapuram, Ravi

2017-08-01

In India, the case fatality ratio of the pandemic A (H1N1) pdm09 influenza was relatively higher when compared to seasonal Influenza A infection. Hypercytokinemia or "cytokine storm" has been previously implicated in the pathogenesis of other influenza viruses. The present study was undertaken to compare the cytokine profiles of A (H1N1) pdm09 influenza and seasonal H3 infection in Indian population and to correlate the findings with disease severity. Plasma levels of 18 cytokines/chemokines were measured by flow-cytometry using a bead based assay in patients infected with A (H1N1) pdm09 virus (n = 96) and Influenza A seasonal H3 virus (n = 30) categorised into mild, moderate, and severe groups along with healthy controls (n = 36). There was an overall trend indicating an exuberant cytokine/chemokine response in A (H1N1) pdm09 as compared to seasonal H3 influenza, which was more evident in severe cases, suggesting a role for these cytokines/chemokines in the pathogenesis of A(H1N1) pdm09. Increased levels of CXCL-8/IL-8, IL-10, IL-6, and IL-17A were seen in both A(H1N1) pdm09 influenza and seasonal H3 cases when compared to healthy controls. However, dysregulated production of proinflammatory chemokines was seen more pronounced in A (H1N1) pdm09 influenza cases as compared to seasonal H3 cases. This study has brought forth the potential role of chemokines as prognostic indicators of disease severity and outcome. Further research on modulating the host immune response to limit severity of the disease could help in the treatment and management of influenza. © 2017 Wiley Periodicals, Inc.

Extrinsic factors significantly affect patterns of disease in free-ranging and captive cheetah (Acinonyx jubatus) populations.

PubMed

Munson, Linda; Terio, Karen A; Worley, Michael; Jago, Mark; Bagot-Smith, Arthur; Marker, Laurie

2005-07-01

The cheetah (Acinonyx jubatus) has been considered a paradigm for disease vulnerability due to loss of genetic diversity. This species monomorphism has been suspected to be the basis for their general poor health and dwindling populations in captivity. North American and South African captive populations have high prevalences of hepatic veno-occlusive disease, glomerulosclerosis, gastritis, and systemic amyloidosis, diseases that are rare in other species. Unusually severe inflammatory reactions to common infectious agents have also been documented in captive cheetahs. The current study compared disease prevalences in free-ranging Namibian cheetahs with those in two captive populations of similar ages. The occurrence of diseases in the free-ranging population was determined from 49 necropsies and 27 gastric biopsies obtained between 1986 and 2003 and compared with prevalences in 147 North American and 80 South African captive cheetahs. Except for two cheetahs, the free-ranging population was in robust health with only mild lesions present, in contrast with significantly higher prevalences in the captive populations. Despite widespread heavy Helicobacter colonization in wild cheetahs, only 3% of the free-ranging population had moderate to severe gastritis, in contrast with 64% of captive cheetahs. No severe inflammatory reactions to viral infections were detected in the free-ranging animals. Because free-ranging Namibian cheetahs are as genetically impoverished as captive cheetahs, these findings caution against attributing loss of fitness solely to genetic factors and attest to the fundamental importance of extrinsic factors in wildlife health.

Seasonality of striatal dopamine synthesis capacity in Parkinson's disease.

PubMed

Kaasinen, Valtteri; Jokinen, Pekka; Joutsa, Juho; Eskola, Olli; Rinne, Juha O

2012-11-14

Recent neuroimaging evidence suggests that the healthy human brain dopaminergic system may show seasonal rhythmicity, as striatal dopamine synthesis capacity has been reported to be higher during fall and winter. There is additional evidence about season of birth effects on morbidity in several neuropsychiatric disorders. We investigated possible seasonal changes in dopamine synthesis capacity in a relatively large sample of Parkinson's disease patients. 6-[(18)F]fluoro-l-DOPA brain PET scans for 109 Parkinson's disease patients were performed during different seasons and the effects of season of scanning and season of birth on striatal tracer uptake were studied, controlling for covariates such as age, sex and disease severity. The patients scanned during fall and winter had 15% higher tracer uptake in the right putamen compared to patients scanned during spring and summer (p=0.04). Patients born during winter and spring had 10% higher dopamine synthesis capacity in the left caudate (p=0.008), 8% higher capacity in the right caudate (p=0.04) and 16% higher capacity in the putamen contralateral to the side of predominant motor symptoms (p=0.02) compared to patients born during summer and fall (after correcting for differences in age, sex, disease severity, scanner and season of scanning). The results suggest that there are seasonal oscillations also in the hypoactive dopaminergic system of Parkinson's disease patients. Findings concerning season of birth further suggest that there may be gestational or perinatal seasonal factors, which influence dopaminergic function in adulthood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

New insights of HLA class I association to Behçet's disease in Portuguese patients.

PubMed

Bettencourt, A; Pereira, C; Carvalho, L; Carvalho, C; Patto, J V; Bastos, M; Silva, A M; Barros, R; Vasconcelos, C; Paiva, P; Costa, L; Costa, P P; Mendonça, D; Correia, J; Silva, B M

2008-10-01

Human leukocyte antigen (HLA)-B*51 is a well-known genetic factor associated with Behçet's disease (BD). To analyse the influence of HLA-B*51 and other HLA class I alleles in BD susceptibility in a Portuguese population and its association with disease severity, we studied 78 BD patients and 208 healthy controls. The patients were classified into two severity groups as described by Gul et al. As expected, a higher frequency of HLA-B*51 was found. The frequency of HLA-Cw*16 alleles was significantly higher in patients. Regarding severity, HLA-B*27 frequency was higher in the severe group compared with controls and with the mild group. Thus, HLA-B*51 and HLA-Cw*16 seem to confer susceptibility to BD in this patients. HLA-B*27 may be important as a prognostic factor.

A data-driven feature extraction framework for predicting the severity of condition of congestive heart failure patients.

PubMed

Sideris, Costas; Alshurafa, Nabil; Pourhomayoun, Mohammad; Shahmohammadi, Farhad; Samy, Lauren; Sarrafzadeh, Majid

2015-01-01

In this paper, we propose a novel methodology for utilizing disease diagnostic information to predict severity of condition for Congestive Heart Failure (CHF) patients. Our methodology relies on a novel, clustering-based, feature extraction framework using disease diagnostic information. To reduce the dimensionality we identify disease clusters using cooccurence frequencies. We then utilize these clusters as features to predict patient severity of condition. We build our clustering and feature extraction algorithm using the 2012 National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP) which contains 7 million discharge records and ICD-9-CM codes. The proposed framework is tested on Ronald Reagan UCLA Medical Center Electronic Health Records (EHR) from 3041 patients. We compare our cluster-based feature set with another that incorporates the Charlson comorbidity score as a feature and demonstrate an accuracy improvement of up to 14% in the predictability of the severity of condition.

Younger and Sicker: Comparing Micronesians to Other Ethnicities in Hawaii

PubMed Central

Miyamura, Jill; Yamada, Seiji; Sentell, Tetine

2016-01-01

Objectives. We compared the age at admission and the severity of illness of hospitalized Micronesians with 3 other racial/ethnic groups in Hawaii. Methods. With Hawaii Health Information Corporation inpatient data, we determined the age at admission and the severity of illness for 162 152 adult, non–pregnancy-related hospital discharges in Hawaii from 2010 to 2012. We performed multivariable linear regression analyses within major disease categories by racial/ethnic group. We created disease categories with all patient refined–diagnosis related groups. Results. Hospitalized Micronesians were significantly younger at admission than were comparison racial/ethnic groups across all patient refined–diagnosis related group categories. The severity of illness for Micronesians was significantly higher than was that of all comparison racial/ethnic groups for cardiac and infectious diseases, higher than was that of Whites and Japanese for cancer and endocrine hospitalizations, and higher than was that of Native Hawaiians for substance abuse hospitalizations. Conclusions. Micronesians were hospitalized significantly younger and often sicker than were comparison populations. Our results will be useful to researchers, state governments, and hospitals, providers, and health systems for this vulnerable group. PMID:26691107

Younger and Sicker: Comparing Micronesians to Other Ethnicities in Hawaii.

PubMed

Hagiwara, Megan Kiyomi Inada; Miyamura, Jill; Yamada, Seiji; Sentell, Tetine

2016-03-01

We compared the age at admission and the severity of illness of hospitalized Micronesians with 3 other racial/ethnic groups in Hawaii. With Hawaii Health Information Corporation inpatient data, we determined the age at admission and the severity of illness for 162,152 adult, non-pregnancy-related hospital discharges in Hawaii from 2010 to 2012. We performed multivariable linear regression analyses within major disease categories by racial/ethnic group. We created disease categories with all patient refined-diagnosis related groups. Hospitalized Micronesians were significantly younger at admission than were comparison racial/ethnic groups across all patient refined-diagnosis related group categories. The severity of illness for Micronesians was significantly higher than was that of all comparison racial/ethnic groups for cardiac and infectious diseases, higher than was that of Whites and Japanese for cancer and endocrine hospitalizations, and higher than was that of Native Hawaiians for substance abuse hospitalizations. Micronesians were hospitalized significantly younger and often sicker than were comparison populations. Our results will be useful to researchers, state governments, and hospitals, providers, and health systems for this vulnerable group.

Is Pregnancy Associated with Severe Dengue? A Review of Data from the Rio de Janeiro Surveillance Information System

PubMed Central

Machado, Carolina Romero; Machado, Elizabeth Stankiewicz; Rohloff, Roger Denis; Azevedo, Marina; Campos, Dayse Pereira; de Oliveira, Robson Bruniera; Brasil, Patrícia

2013-01-01

Background Dengue is a reportable disease in Brazil; however, pregnancy has been included in the application form of the Brazilian notification information system only after 2006. To estimate the severity of maternal dengue infection, the available data that were compiled from January 2007 to December 2008 by the official surveillance information system of the city of Rio de Janeiro were reviewed. Methods and Principal Findings During the study period, 151,604 cases of suspected dengue infection were reported. Five hundred sixty-one women in their reproductive age (15–49 years) presented with dengue infection; 99 (18.1%) pregnant and 447 (81.9%) non-pregnant women were analyzed. Dengue cases were categorized using the 1997 WHO classification system, and DHF/DSS were considered severe disease. The Mann-Whitney test was used to compare maternal age, according to gestational period, and severity of disease. A chi-square test was utilized to evaluate the differences in the proportion of dengue severity between pregnant and non-pregnant women. Univariate analysis was performed to compare outcome variables (severe dengue and non-severe dengue) and explanatory variables (pregnancy, gestational age and trimester) using the Wald test. A multivariate analysis was performed to assess the independence of statistically significant variables in the univariate analysis. A p-value<0.05 was considered statistically significant. A higher percentage of severe dengue infection among pregnant women was found, p = 0.0001. Final analysis demonstrated that pregnant women are 3.4 times more prone to developing severe dengue (OR: 3.38; CI: 2.10–5.42). Mortality among pregnant women was superior to non-pregnant women. Conclusion Pregnant women have an increased risk of developing severe dengue infection and dying of dengue. PMID:23675548

Clinical and Phenotypic Differences in Inflammatory Bowel Disease Among Arab and Jewish Children in Israel.

PubMed

Rinawi, Firas; Assa, Amit; Bashir, Husam; Peleg, Sarit; Shamir, Raanan

2017-08-01

Data on inflammatory bowel disease (IBD) phenotypes among the Arab population in Israel or in the neighboring Arab countries is scarce. We aimed to assess differences in disease phenotype among Arab and Jewish children living in Israel. We performed a retrospective chart review of pediatric IBD cases, which were diagnosed at the Schneider Children's Medical Center and Ha'Emek Medical Center in Israel between 2000 and 2014. Demographic, clinical, and phenotypic variables were compared between Arabs and Jews from Eastern (Sephardic) and Western (Ashkenazi) origin. Seventy-one Arab children with IBD were compared with 165 Ashkenazi and 158 Sephardic Jewish children. Age and gender did not differ between groups. Sephardic and Ashkenazi Jewish Crohn's disease (CD) patients had significantly more stenotic behavior (24 and 26 vs. 5%, p = 0.03) and less fistulzing perianal disease (15 and 11 vs. 31%, p = 0.014) compared with Arab patients. Arab children with ulcerative colitis (UC) had more severe disease at diagnosis compared to Sephardic and Ashkenazi Jews reflected by higher Pediatric UC Activity Index (45 vs. 35 and 35, respectively, p = 0.03). Arab patients had significantly lower proportion of anti-Saccharomyces cerevisiae antibodies positivity (in CD) and perinuclear anti-neutrophil cytoplasmic antibodies positivity (in UC) than both Sephardic and Ashkenazi Jewish children (23 vs. 53 and 65%, p = 0.002 and 35 vs. 60 and 75%, respectively, p = 0.002). Arab and Jewish children with IBD differ in disease characteristics and severity. Whether genetic or environmental factors are the cause for these differences is yet to be determined.

Murmur intensity in adult dogs with pulmonic and subaortic stenosis reflects disease severity.

PubMed

Caivano, D; Dickson, D; Martin, M; Rishniw, M

2018-03-01

The aims of this study were to determine whether murmur intensity in adult dogs with pulmonic stenosis or subaortic stenosis reflects echocardiographic disease severity and to determine whether a six-level murmur grading scheme provides clinical advantages over a four-level scheme. In this retrospective multi-investigator study on adult dogs with pulmonic stenosis or subaortic stenosis, murmur intensity was compared to echocardiographically determined pressure gradient across the affected valve. Disease severity, based on pressure gradients, was assessed between sequential murmur grades to identify redundancy in classification. A simplified four-level murmur intensity classification scheme ('soft', 'moderate', 'loud', 'palpable') was evaluated. In total, 284 dogs (153 with pulmonic stenosis, 131 with subaortic stenosis) were included; 55 dogs had soft, 59 had moderate, 72 had loud and 98 had palpable murmurs. 95 dogs had mild stenosis, 46 had moderate stenosis, and 143 had severe stenosis. No dogs with soft murmurs of either pulmonic or subaortic stenosis had transvalvular pressure gradients greater than 50 mmHg. Dogs with loud or palpable murmurs mostly, but not always, had severe stenosis. Stenosis severity increased with increasing murmur intensity. The traditional six-level murmur grading scheme provided no additional clinical information than the four-level descriptive murmur grading scheme. A simplified descriptive four-level murmur grading scheme differentiated stenosis severity without loss of clinical information, compared to the traditional six-level scheme. Soft murmurs in dogs with pulmonic or subaortic stenosis are strongly indicative of mild lesions. Loud or palpable murmurs are strongly suggestive of severe stenosis. © 2017 British Small Animal Veterinary Association.

DNA vaccines in veterinary use

PubMed Central

Redding, Laurel; Werner, David B

2015-01-01

DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

Strategies to Prevent, Treat, and Provoke Corynebacterium-Associated Hyperkeratosis in Athymic Nude Mice

PubMed Central

Burr, Holly N; Lipman, Neil S; White, Julie R; Zheng, Junting; Wolf, Felix R

2011-01-01

Athymic nude mice infected with Corynebacterium bovis typically exhibit transient hyperkeratotic dermatitis. Our vivarium experienced an increased incidence of disease characterized by persistent skin lesions and increased mortality, leading to this study. For detection of infection, skin and buccal swab methods showed comparable sensitivities in nude mice. Various prevention, treatment, and eradication strategies were evaluated through clinical assessment, microbiology, and histopathology. In experimentally naïve athymic nude mice, a 2-wk course of prophylactic amoxicillin-containing diet (1200 ppm amoxicillin; effective dose, 200 mg/kg) was ineffective at preventing infection or disease. There was also no significant difference in disease duration or severity in athymic nude mice that received amoxicillin diet or penicillin–streptomycin topical spray (penicillin, 2500 U/mL; streptomycin, 2500 µg/mL). Prolonged treatment with 4 or 8 wk of amoxicillin diet cleared only a small number of athymic nude mice that had subclinical C. bovis infections. Antibiotic sensitivity of C. bovis isolates demonstrated a small colony isolate with less susceptibility to all antibiotics compared with a large colony isolate. Resistance did not appear to develop after prolonged treatment with amoxicillin. Provocation testing by administration of cyclophosphamide (50 mg/kg IP every 48 to 72 h for 90 d) to subclinically infected athymic nude mice resulted in prolonged clinical disease that waxed and waned without progression to severe disease. Our findings suggest that antibiotic prophylaxis and treatment of clinical disease in experimentally naïve mice is unrewarding, eradication of bacterial infection is difficult, and severe disease associated with C. bovis is likely multifactorial. PMID:21640035

Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease.

PubMed

He, Zhangping; Tang, Yanyan; Qin, Chao

2017-06-01

Circulating leukocyte-derived microparticles act as proinflammatory mediators that reflect vascular inflammation. In this study, we examined the hypothesis that the quantity of leukocyte-derived microparticles is increased in patients with ischemic cerebrovascular diseases, and investigated utility of various phenotypes of leukocyte-derived microparticles as specific biomarkers of vascular inflammation injury. Additionally we focused on identifying leukocyte-derived microparticles that may be correlated with stroke severity in acute ischemic stroke patients. The plasma concentration of leukocyte-derived microparticles obtained by a series of centrifugations of 76 consecutive patients with ischemic cerebrovascular diseases and 70 age-, sex-, and race-matched healthy controls were determined by flow cytometry. Significantly elevated numbers of leukocyte (CD45+), monocyte (CD14+), lymphocyte (CD4+), granulocyte (CD15+) derived microparticles were found in the plasma samples of patients ischemic cerebrovascular diseases, compared to healthy controls (p<0.05). Furthermore, the plasma levels of CD14+ microparticles were significantly correlated with stroke severity (r=0.355, p=0.019), cerebral vascular stenosis severity (r=0.255, p=0.025) and stroke subtype (r=0.242, p=0.036). No association with stroke was observed for other leukocyte-derived phenotypes. These results demonstrate that circulating leukocyte-derived microparticles amounts are increased in patients with ischemic cerebrovascular diseases, compared with healthy controls. As proinflammatory mediators, leukocyte-derived microparticles may contribute to vascular inflammatory and the inflammatory process in acute ischemic stroke. Levels of CD14+ microparticles may be a promising biomarker of ischemic severity and outcome of stroke in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease.

PubMed

Li, Yan; Wang, Wei; Lv, Zhe; Li, Yun; Chen, Yan; Huang, Kewu; Corrigan, Chris J; Ying, Sun

2018-04-01

The epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been implicated in asthma pathogenesis because they promote Th2-type cytokine synthesis, but their expression is relatively poorly documented in "real-life" human asthma. Using bronchoalveolar lavage fluid (BALF), we measured airway concentrations of these mediators and compared them with those of Th1- and Th2-type cytokines, airway infiltration of neutrophils and eosinophils, and lung function in a large group of asthmatic patients with a range of disease severity ( n = 70) and control subjects ( n = 30). The median BALF concentrations of IL-33, TSLP, IL-4, IL-5, IL-13, and IL-12p70, but not IL-25, IL-2, or IFN-γ, were significantly elevated in asthmatics compared with controls ( p < 0.05). The concentrations of IL-33 and TSLP, but not IL-25, correlated inversely with the lung function (forced expiratory volume in the first second) of asthmatics (IL-33: r = -0.488, p < 0.0001; TSLP: r = -0.565, p < 0.0001) independently of corticosteroid therapy. When divided according to disease severity and corticosteroid therapy, all subgroups of asthmatics had elevated median numbers of eosinophils in BALF, whereas the patients with more severe disease who were treated with corticosteroids had higher numbers of neutrophils compared with milder asthmatics not so treated and control subjects ( p < 0.05). The data implicate TSLP and IL-33 in the pathogenesis of asthma that is characterized by persistent airway inflammation and impaired lung function despite intensive corticosteroid therapy, highlighting them as potential molecular targets. Copyright © 2018 by The American Association of Immunologists, Inc.

Re-emergent tremor in Parkinson's disease: Clinical and accelerometric properties.

PubMed

Aytürk, Zübeyde; Yilmaz, Rezzak; Akbostanci, M Cenk

2017-03-01

Re-emergent tremor (RET) and the classical parkinsonian rest tremor were considered as two different phenomena of the same central tremor circuit. However, clinical and accelerometric characteristics of these tremors were not previously compared in a single study. We evaluated disease characteristics and accelerometric measurements of two tremor types in 42 patients with Parkinson's disease. Disease specific features and accelerometric measurements of peak frequency, amplitude at peak frequency and the root mean square (RMS) amplitude of two tremor types were compared. Eighteen patients had RET and the mean latency of the RET was 9.48 (±9.2)s. Groups of only rest tremor and RET did not differ significantly in age of disease onset, disease duration and severity and mean levodopa equivalent dose. Comparison of peak frequency and amplitude at peak frequency were not different between the groups, but RMS amplitude was significantly higher in the RET group (p=0.03). RMS amplitude of RET was also correlated with disease severity (r=.48, p=0.04). These results support the previous notion that rest tremor and RET are analogue, both are triggered by the same central ossilator with RET being only the suppression of the rest tremor due to arm repositioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fall and Fracture Risk in Nursing Home Residents With Moderate-to-Severe Behavioral Symptoms of Alzheimer's Disease and Related Dementias Initiating Antidepressants or Antipsychotics.

PubMed

Wei, Yu-Jung; Simoni-Wastila, Linda; Lucas, Judith A; Brandt, Nicole

2017-05-01

Both antidepressants and antipsychotics are used in older adults with behavioral symptoms of Alzheimer's disease and related dementias. Despite the prevalent use of these agents, little is known about their comparative risks for falls and fractures. Using 2007-2009 Medicare claims data linked to Minimum Data Set 2.0, we identified new users of antidepressants and antipsychotics among nursing home residents with Alzheimer's disease and related dementias who had moderate-to-severe behavioral symptoms. Separate discrete-time survival models were used to estimate risks of falls, fractures, and a composite of both among antidepressant group versus antipsychotic group. Compared to antipsychotic users, antidepressant users experienced significantly higher risk for fractures (adjusted hazard ratio = 1.35, 95% confidence interval = 1.10-1.66). The overall risk of falls or fractures remained significant in the antidepressant versus antipsychotic group (adjusted hazard ratio = 1.16, 95% confidence interval = 1.02-1.32). Antidepressants are associated with higher fall and fracture risk compared to antipsychotics in the management of older adults with Alzheimer's disease and related dementias who experience moderate-to-severe behavioral symptoms. Clinicians need to assess the ongoing risks/benefits of antidepressants for these symptoms especially in light of the increasingly prevalent use of these agents. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Systemic lupus erythematosus and thyroid disease - Experience in a single medical center in Taiwan.

PubMed

Liu, Yu-Chuan; Lin, Wen-Ya; Tsai, Ming-Chin; Fu, Lin-Shien

2017-06-28

To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001). SLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement. Copyright © 2017. Published by Elsevier B.V.

Disease Control Among Patients With Diabetes and Severe Depressive Symptoms.

PubMed

Werremeyer, Amy; Maack, Brody; Strand, Mark A; Barnacle, Mykell; Petry, Natasha

2016-04-01

Major depressive disorder and type 2 diabetes commonly co-occur and disease control tends to be poorer when both conditions are present. However, little research has examined the disease characteristics of patients with diabetes and more severe depressive symptoms. We report a retrospective observational study of 517 patients with diabetes from 2 primary care centers. Patients with diabetes and moderately-severe/severe depression symptoms (Patient Health Questionnaire [PHQ-9] score >15) were compared with patients with diabetes without moderate or severe depression symptoms (PHQ-9 score <15; the comparison group) with regard to control of diabetes, blood pressure, and lipid parameters. Frequency of HbA1c and PHQ-9 testing were also examined. Patients with diabetes and moderately severe/severe depressive symptoms had higher HbA1c (7.56% vs. 7.09%), diastolic blood pressure (78.43 vs. 75.67 mm Hg), and low-density lipoprotein cholesterol (109.12 vs. 94.22 mg/dL) versus the comparison group. Patients with diabetes and moderately-severe/severe depression underwent HbA1c and PHQ-9 testing with similar frequency to the comparison group. The presence of moderately severe/severe depressive symptoms was associated with poorer glucose, lipid, and blood pressure control among patients with diabetes. Further research should prospectively examine whether a targeted depression treatment goal (PHQ-9 score <15) in patients with diabetes results in improved control of these important disease parameters. © The Author(s) 2016.

Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

PubMed Central

Fite, Alemu; Furrie, Elizabeth; Bahrami, Bahram; Cummings, John H.; Steinke, Douglas T.; Macfarlane, George T.

2013-01-01

Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity. PMID:23269735

Virus Type and Genomic Load in Acute Bronchiolitis: Severity and Treatment Response With Inhaled Adrenaline.

PubMed

Skjerven, Håvard O; Megremis, Spyridon; Papadopoulos, Nikolaos G; Mowinckel, Petter; Carlsen, Kai-Håkon; Lødrup Carlsen, Karin C

2016-03-15

Acute bronchiolitis frequently causes infant hospitalization. Studies on different viruses or viral genomic load and disease severity or treatment effect have had conflicting results. We aimed to investigate whether the presence or concentration of individual or multiple viruses were associated with disease severity in acute bronchiolitis and to evaluate whether detected viruses modified the response to inhaled racemic adrenaline. Nasopharyngeal aspirates were collected from 363 infants with acute bronchiolitis in a randomized, controlled trial that compared inhaled racemic adrenaline versus saline. Virus genome was identified and quantified by polymerase chain reaction analyses. Severity was assessed on the basis of the length of stay and the use of supportive care. Respiratory syncytial virus (83%) and human rhinovirus (34%) were most commonly detected. Seven other viruses were present in 8%-15% of the patients. Two or more viruses (maximum, 7) were detected in 61% of the infants. Virus type or coinfection was not associated with disease severity. A high genomic load of respiratory syncytial virus was associated with a longer length of stay and with an increased frequency of oxygen and ventilatory support use. Treatment effect of inhaled adrenaline was not modified by virus type, load or coinfection. In infants hospitalized with acute bronchiolitis, disease severity was not associated with specific viruses or the total number of viruses detected. A high RSV genomic load was associated with more-severe disease. NCT00817466 and EudraCT 2009-012667-34. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Prevalence of bacteria and fungi in athlete's foot of varying severity and response to topical antibacterial and antifungal therapies.

PubMed

Talwar, P; Kumar, B; Ayyagiri, A; Kaur, S

1985-08-01

Ninety-six patients with clinical evidence of interdigital lesions classified as mild, moderate and severe athlete's foot were investigated for bacterial and fungal populations in the interspaces. Gram-negative bacteria, which were not found in the toe spaces of 50 normal controls, were grown in increasing numbers and with increasing frequency as the symptoms progressed from mild to severe. Gram-positive bacteria were also isolated regularly and in increasing numbers commensurate with the severity of the disease. Similarly the isolation rates of dermatophytes and Candida species were higher in patients with moderate and severe disease compared to those with mild disease. Clinical and culture responses to topical applications with framycetin, tolnaftate, miconazole and clotrimazole were also studied. In some patients the prevalence of pathogenic fungi increased as bacterial numbers decreased. The pure antibacterial framycetin brought symptomatic relief, as did the purely anti-dermatophyte substance tolnaftate, but best results were seen with two azole compounds having mixed antibacterial and antifungal properties.

Parenting Stress Related to Behavioral Problems and Disease Severity in Children with Problematic Severe Asthma.

PubMed

Verkleij, Marieke; van de Griendt, Erik-Jonas; Colland, Vivian; van Loey, Nancy; Beelen, Anita; Geenen, Rinie

2015-09-01

Our study examined parenting stress and its association with behavioral problems and disease severity in children with problematic severe asthma. Research participants were 93 children (mean age 13.4 ± 2.7 years) and their parents (86 mothers, 59 fathers). As compared to reference groups analyzed in previous research, scores on the Parenting Stress Index in mothers and fathers of the children with problematic severe asthma were low. Higher parenting stress was associated with higher levels of internalizing and externalizing behavioral problems in children (Child Behavior Checklist). Higher parenting stress in mothers was also associated with higher airway inflammation (FeNO). Thus, although parenting stress was suggested to be low in this group, higher parenting stress, especially in the mother, is associated with more airway inflammation and greater child behavioral problems. This indicates the importance of focusing care in this group on all possible sources of problems, i.e., disease exacerbations and behavioral problems in the child as well as parenting stress.

Percutaneous intervention for infrainguinal occlusive disease in women: equivalent outcomes despite increased severity of disease compared with men.

PubMed

DeRubertis, Brian G; Vouyouka, Angela; Rhee, Soo J; Califano, Joseph; Karwowski, John; Angle, Niren; Faries, Peter L; Kent, K Craig

2008-07-01

Experience with open surgical bypass suggests similar overall outcomes in women compared with men, but significantly increased risk of wound complications. Percutaneous treatment of lower extremity occlusive disease is therefore an attractive alternative in women, although it is not clear whether there is a difference in outcomes between women and men treated with this technique. We sought to determine the results and predictors of failure in women treated by percutaneous intervention. Percutaneous infrainguinal revascularization was performed on 309 women between 2001 and 2006. Procedures, complications, demographics, comorbidities, and follow-up data were entered into a prospective database for review. Patency was assessed primarily by duplex ultrasonography. Outcomes were expressed by Kaplan-Meier curves and compared by log-rank analysis. A total of 447 percutaneous interventions performed in 309 women were analyzed and compared with 553 interventions in men. Mean age in women was 73.2 years; comorbidities included hypertension (HTN) (86%), diabetes melitus (DM) (58%), chronic renal insufficiency (CRI) (15%), hemodialysis (7%), hypercholesterolemia (52%), coronary artery disease (CAD) (42%), and tobacco use (47%). Indications in women included claudication (38.0%), rest pain (18.8%), and tissue loss (43.2%). Overall primary & secondary patency and limb-salvage rates for women were 38% +/- 4%, 66% +/- 3%, and 80% +/- 4% at 24 months. In this patient sample, women were significantly more likely than men to present with limb-threatening ischemia (61.6% vs 47.3%, P < 0.001) and have lesions of TASC C and D severity (71.4% vs 61.7%, P < .005). However, there were no significant differences in primary and secondary patency rates or limb-salvage rates between genders. Furthermore, while women with limb-threat, diabetes, and advanced TASC severity lesions were at increased risk of failure overall, there were no differences between women and men with these characteristics. Percutaneous infrainguinal revascularization is a very effective modality in women with lower extremity occlusive disease. Although women in this sample were more likely to present with limb-threat than men, patency and limb-salvage rates were equivalent between genders, even in high-risk subsets such as diabetics or those with lesions of increased TASC severity.

MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden.

PubMed

Banerjee, Gargi; Kim, Hee Jin; Fox, Zoe; Jäger, H Rolf; Wilson, Duncan; Charidimou, Andreas; Na, Han Kyu; Na, Duk L; Seo, Sang Won; Werring, David J

2017-04-01

Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment. We also hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with brain amyloid burden, as detected by amyloid positron emission tomography using 11C-Pittsburgh B compound (PiB-PET). Two hundred and twenty-six patients (Alzheimer's disease n = 110; subcortical vascular cognitive impairment n = 116) with standardized MRI and PiB-PET imaging were included. MRI-visible perivascular spaces were rated using a validated 4-point visual rating scale, and then categorized by severity ('none/mild', 'moderate' or 'frequent/severe'). Univariable and multivariable regression analyses were performed. Those with Alzheimer's disease-related cognitive impairment were younger, more likely to have a positive PiB-PET scan and carry at least one apolipoprotein E ɛ4 allele; those with subcortical vascular cognitive impairment were more likely to have hypertension, diabetes mellitus, hyperlipidaemia, prior stroke, lacunes, deep microbleeds, and carry the apolipoprotein E ɛ3 allele. In adjusted analyses, the severity of MRI-visible perivascular spaces in the centrum semi-ovale was independently associated with clinically diagnosed Alzheimer's disease (frequent/severe grade odds ratio 6.26, 95% confidence interval 1.66-23.58; P = 0.017, compared with none/mild grade), whereas the severity of MRI-visible perivascular spaces in the basal ganglia was associated with clinically diagnosed subcortical vascular cognitive impairment and negatively predicted Alzheimer's disease (frequent/severe grade odds ratio 0.03, 95% confidence interval 0.00-0.44; P = 0.009, compared with none/mild grade). MRI-visible perivascular space severity in either location did not predict PiB-PET. These findings provide further evidence that the anatomical distribution of MRI-visible perivascular spaces may reflect the underlying cerebral small vessel disease. Using MRI-visible perivascular space location and severity together with other imaging markers may improve the diagnostic value of neuroimaging in memory clinic populations, in particular in differentiating between clinically diagnosed Alzheimer's and subcortical vascular cognitive impairment. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

PubMed

Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

2016-04-01

Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

Towards personalizing haemophilia care: using the Haemophilia Severity Score to assess 178 patients in a single institution.

PubMed

Vyas, S; Enockson, C; Hernandez, L; Valentino, L A

2014-01-01

The phenotypic variability in haemophilia is well documented; however, the biological basis beyond factor VIII and IX activities to explain the differing clinical pictures of the disease remains unclear. It has therefore been of interest to explore other modulators of the disease's variability. Furthermore, a scoring system that reflects the multiple facets of haemophilia symptoms would be useful to compare patients via a comprehensive assessment tool. To this end, Schulman et al., created a measure known as the Haemophilia Severity Score (HSS) as one way to compare phenotypic severity. The aim of this study was to document the differing symptomatology of haemophilia patients using the HSS. Clinical data for 178 haemophilia patients without inhibitors were reviewed and annual incidence of haemarthrosis, orthopaedic joint scores and annual factor usage calculated. Each parameter was then entered into the formula to create the HSS for haemophilia A and B patients with mild, moderate and severe factor deficiencies. Variability in the HSS for patients with the same baseline level of factor was observed for all three deficiency levels and both haemophilia types. In addition, we found that moderate and severe haemophilic B patients tended to have more morbidity based on the above calculations than the haemophilic A counterparts. The HSS is a comprehensive tool that allows for easy numerical comparison of haemophilic patients and elucidates the variable clinical presentation of the disease. The HSS could be used to stratify patients via other possible modulators of haemophilia and discover other aetiologies of the disease. © 2013 John Wiley & Sons Ltd.

Periodontitis in Chronic Heart Failure

PubMed Central

Fröhlich, Hanna; Herrmann, Kristina; Franke, Jennifer; Karimi, Alamara; Täger, Tobias; Cebola, Rita; Katus, Hugo A.; Zugck, Christian

2016-01-01

Periodontal disease has been associated with an increased risk of cardiovascular events. The purpose of our study was to investigate whether a correlation between periodontitis and chronic heart failure exists, as well as the nature of the underlying cause. We enrolled 71 patients (mean age, 54 ± 13 yr; 56 men) who had stable chronic heart failure; all underwent complete cardiologic and dental evaluations. The periodontal screening index was used to quantify the degree of periodontal disease. We compared the findings to those in the general population with use of data from the 4th German Dental Health Survey. Gingivitis, moderate periodontitis, and severe periodontitis were present in 17 (24%), 17 (24%), and 37 (52%) patients, respectively. Severe periodontitis was more prevalent among chronic heart failure patients than in the general population. In contrast, moderate periodontitis was more prevalent in the general population (P <0.00001). The severity of periodontal disease was not associated with the cause of chronic heart failure or the severity of heart failure symptoms. Six-minute walking distance was the only independent predictor of severe periodontitis. Periodontal disease is highly prevalent in chronic heart failure patients regardless of the cause of heart failure. Prospective trials are warranted to clarify the causal relationship between both diseases. PMID:27547136

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

PubMed Central

Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

2011-01-01

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study

PubMed Central

2013-01-01

Background Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP). Methods In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function. Results All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients. Conclusion Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction. PMID:23705943

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

PubMed

van den Bosch, Harrie C M; Westenberg, Jos J M; Setz-Pels, Wikke; Wondergem, John; Wolterbeek, Ron; Duijm, Lucien E M; Teijink, Joep A W; de Roos, Albert

2015-01-20

Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery. Forty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression. Stenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender. Distal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular territories such as proximal aortic wall stiffness or carotid arterial wall thickness. Site-specific evaluation of vascular disease may be required for full vascular risk estimation.

Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

PubMed

McAdoo, Stephen P; Tanna, Anisha; Hrušková, Zdenka; Holm, Lisa; Weiner, Maria; Arulkumaran, Nishkantha; Kang, Amy; Satrapová, Veronika; Levy, Jeremy; Ohlsson, Sophie; Tesar, Vladimir; Segelmark, Mårten; Pusey, Charles D

2017-09-01

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Determinants of marginal traction alopecia in African girls and women.

PubMed

Khumalo, Nonhlanhla P; Jessop, Susan; Gumedze, Freedom; Ehrlich, Rodney

2008-09-01

Our recent population studies reported a prevalence of traction alopecia (TA) of 17.1% in African schoolgirls (6-21 years) and of 31.7% in women (18-86 years). More schoolgirls had chemically treated hair than women and disease presence was associated with hairstyles. The aim of this study was to investigate determinants of TA presence and severity in girls and women using data from both studies. Clinical assessment and a Marginal TA Severity score were used for diagnosis and disease severity, respectively. The data used included 574 schoolgirls and 604 women. The first analysis was multiple logistic regression for disease presence. Exploratory associations for disease severity were assessed using the Spearman rank correlation test. Adults were defined as age 18 years or older, irrespective of study. The odds ratio for TA was higher in adults than in children (<18 years) (1.87 [P < .001, 95% confidence interval 1.28-2.72]) and was higher with braiding-related than chemical-related symptoms. The highest risk of TA, compared with natural hair, occurred when traction was added to relaxed hair (odds ratio 3.47 [P < .001, 95% confidence interval 1.94-6.20]). Only 18.9% of patients with TA had never had symptoms related to hairdressing. TA severity was associated with age group, current hairstyle, and hairdressing symptoms. Participants with severe disease were too few to estimate determinants. There is a need for the validation of the Marginal TA Severity score with larger numbers and for future studies to include more participants with severe disease. Our findings suggest that avoiding both hairdressing symptoms and the addition of traction, especially to chemically processed hair, may reduce the risk of developing TA.

The impact of pediatric nephrotic syndrome on families.

PubMed

Mitra, Sulagna; Banerjee, Sushmita

2011-08-01

The objective of our study was to assess the psychologic and economic effects of pediatric nephrotic syndrome (NS) on caregivers. Caregivers of 50 children with NS were compared with a control group of 50 families of children with minor illnesses attending the same outpatient facility. Beck's Depression Inventory (BDI) IA was used to assess the mental status of the primary caregiver. The socioeconomic status of the family was assessed using the modified Kuppuswamy scale. Expenditure for the illness was calculated during parent interviews. The difference between groups was analyzed using analysis of variance (ANOVA) and Duncan's multiple range test. BDI scores signified moderate to severe depression in 48% of NS caregivers compared with 12% controls. The mean BDI score was significantly higher in NS caregivers, correlating positively with disease severity and negatively with socioeconomic status. Expenditure for disease also was significantly higher in families with NS patients, varying between 30% and 60% of monthly income depending on disease severity compared with 6.9% in controls. In 10% of NS families, it was more than total income, forcing families to break into savings or go into debt. Although pediatric NS most commonly has an excellent long-term outcome, it causes significant mental and economic stress on families. Severe forms should be categorized as a chronic illness and be eligible for disability benefits and subsidized travel and medical care. Establishing support groups and supportive care at local levels would help reduce the burden on families of patients wtih NS.

Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus.

PubMed

Angulo, Jenniffer; Martínez-Valdebenito, Constanza; Marco, Claudia; Galeno, Héctor; Villagra, Eliecer; Vera, Lilian; Lagos, Natalia; Becerra, Natalia; Mora, Judith; Bermúdez, Andrea; Díaz, Janepsy; Ferrés, Marcela; López-Lastra, Marcelo

2017-07-01

Andes virus (ANDV) is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1β concentration were observed in ANDV-infected patients (p = 0.9672), whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001). Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively). Notably, IL-6 levels were significantly higher (40-fold) in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001). Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3-63.1). In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.

Levels of physical activity in patients with severe psoriasis: a cross-sectional questionnaire study.

PubMed

Torres, Tiago; Alexandre, José Manuel; Mendonça, Denisa; Vasconcelos, Carlos; Silva, Berta Martins; Selores, Manuela

2014-04-01

Psoriasis is a chronic inflammatory disease associated with increased cardiovascular mortality, secondary to the increased prevalence of cardiovascular risk factors and premature atherosclerosis. Physical activity is a vital component in prevention and management of cardiovascular disease. Few studies have examined the level of physical activity in psoriasis patients, using validated questionnaires or other objective assessment tools. The aim of this study was to analyze and compare physical activity undertaken by patients with severe psoriasis and healthy controls, using the International Physical Activity Questionnaire-Short Form (IPAQ-S), a validated instrument for assessing physical activity. Ninety patients with severe plaque-type psoriasis and 160 healthy subjects were enrolled in the present study. Physical activity was evaluated using IPAQ-S. Psoriasis patients had reduced levels of physical activity compared with non-psoriasis patients, regardless of sex or whether the variable was continuous or categorical. The odds ratio for low-level physical activity for psoriasis patients, compared with controls, was 3.42 (95% CI 1.47-7.91), indicating that this severe psoriasis population did not undertake recommended levels of physical activity. Psoriasis patients exhibit decreased levels of physical activity, possibly for both psychological and physiological reasons. The lack of physical activity may contribute to the increased risk of cardiovascular disease in psoriasis patients, in addition to the intrinsic risks related to systemic inflammation and psoriasis-linked comorbidities. Regular physical activity should be encouraged in all psoriasis patients because of its beneficial effects on systemic inflammation and cardiometabolic comorbidities associated with psoriasis.

Ethnicity influences disease characteristics and symptom severity in allergic rhinitis patients in Malaysia.

PubMed

Amini, Peyman; Abdullah, Maha; Seng, Lee Sing; Karunakaran, Thanusha; Hani, Norzhafarina; Bakar, Saraiza Abu; Latiff, Amir Hamzah Abdul; Fong, Seow Heng; Yeow, Yap Yoke

2016-06-01

The number of available reports regarding the influence of ethnicity on clinical features of allergic rhinitis (AR), especially disease severity in tropical climates, is limited. We aimed to compare clinical parameters and disease severity in AR patients of different ethnicities. Malay, Chinese, and Indian AR patients (n = 138) with confirmed sensitivity to Dermatophagoides pteronyssinus, Dematophagoides farinae, and Blomia tropicalis were tested for mite-specific immunoglobulin E (sIgE) levels. A detailed questionnaire was used to collect data on nasal symptom score (NSS), ocular symptom score (OSS), sum of symptoms score (SSS), quality of life score (QLS), symptomatic control score (SCS), and total sum of scores (TSS) and correlate the derived data with patients' demography, mite-polysensitivity, and sIgE levels. AR-related symptoms were most severe in Malays and least in Chinese (p < 0.01). Age (r = 0.516 to 0.673, p < 0.05) and duration of AR (r = 0.635 to 0.726, p < 0.01) correlated positively with severity domains (NSS, SSS, QLS, and TSS) in Chinese. Duration of concurrent allergies was highest in Malays (p < 0.05). Polysensitivity predicted increased sIgE levels in Malays (r = 0.464 to 0.551, p < 0.01) and Indians (r = 0.541 to 0.645, p < 0.05) but affected NSS, SSS, and TSS only in Indians (r = 0.216 to 0.376, p < 0.05). sIgE levels were lowest among Chinese but correlated strongly with NSS, OSS, SSS, and TSS (r = 0408 to 0.898, p < 0.05). Clinical parameters in AR may be influenced by race. Symptoms were most severe among Malays but did not correlate with other variables examined. Although Indian ethnicity did not impact disease severity, duration of concurrent allergies and mite-polysensitivity was associated with more severe disease. Age, duration of disease, and sIgE levels may be useful indicators of disease severity in Chinese. © 2016 ARS-AAOA, LLC.

Hyperspectral and chlorophyll fluorescence imaging to analyse the impact of Fusarium culmorum on the photosynthetic integrity of infected wheat ears.

PubMed

Bauriegel, Elke; Giebel, Antje; Herppich, Werner B

2011-01-01

Head blight on wheat, caused by Fusarium spp., is a serious problem for both farmers and food production due to the concomitant production of highly toxic mycotoxins in infected cereals. For selective mycotoxin analyses, information about the on-field status of infestation would be helpful. Early symptom detection directly on ears, together with the corresponding geographic position, would be important for selective harvesting. Hence, the capabilities of various digital imaging methods to detect head blight disease on winter wheat were tested. Time series of images of healthy and artificially Fusarium-infected ears were recorded with a laboratory hyperspectral imaging system (wavelength range: 400 nm to 1,000 nm). Disease-specific spectral signatures were evaluated with an imaging software. Applying the 'Spectral Angle Mapper' method, healthy and infected ear tissue could be clearly classified. Simultaneously, chlorophyll fluorescence imaging of healthy and infected ears, and visual rating of the severity of disease was performed. Between six and eleven days after artificial inoculation, photosynthetic efficiency of infected compared to healthy ears decreased. The severity of disease highly correlated with photosynthetic efficiency. Above an infection limit of 5% severity of disease, chlorophyll fluorescence imaging reliably recognised infected ears. With this technique, differentiation of the severity of disease was successful in steps of 10%. Depending on the quality of chosen regions of interests, hyperspectral imaging readily detects head blight 7 d after inoculation up to a severity of disease of 50%. After beginning of ripening, healthy and diseased ears were hardly distinguishable with the evaluated methods.

Virulence of plant pathogenic bacteria attenuated by degradation of fatty acid cell-to-cell signaling factors.

PubMed

Newman, Karyn L; Chatterjee, Subhadeep; Ho, Kimberly A; Lindow, Steven E

2008-03-01

Diffusible signal factor (DSF) is a fatty acid signal molecule involved in regulation of virulence in several Xanthomonas species as well as Xylella fastidiosa. In this study, we identified a variety of bacteria that could disrupt DSF-mediated induction of virulence factors in Xanthomonas campestris pv. campestris. While many bacteria had the ability to degrade DSF, several bacterial strains belonging to genera Bacillus, Paenibacillus, Microbacterium, Staphylococcus, and Pseudomonas were identified that were capable of particularly rapid degradation of DSF. The molecular determinants for rapid degradation of DSF in Pseudomonas spp. strain G were elucidated. Random transposon mutants of strain G lacking the ability to degrade DSF were isolated. Cloning and characterization of disrupted genes in these strains revealed that carAB, required for the synthesis of carbamoylphosphate, a precursor for pyrimidine and arginine biosynthesis is required for rapid degradation of DSF in strain G. Complementation of carAB mutants restored both pyrimidine prototrophy and DSF degradation ability of the strain G mutant. An Escherichia coli strain harboring carAB of Pseudomonas spp. strain G degrades DSF more rapidly than the parental strain, and overexpression of carAB in trans increased the ability of Pseudomonas spp. strain G to degrade as compared with the parental strain. Coinoculation of X. campestris pv. campestris with DSF-degrading bacteria into mustard and cabbage leaves reduced disease severity up to twofold compared with plants inoculated only with the pathogen. Likewise, disease incidence and severity in grape stems coinoculated with Xylella fastidiosa and DSF-degrading strains were significantly reduced compared with plants inoculated with the pathogen alone. Coinoculation of grape plants with a carAB mutant of Pseudomonas spp. strain G complemented with carAB in trans reduced disease severity as well or better than the parental strain. These results indicate that overexpression of carAB in other endophytes could be a useful strategy of biocontrol for the control of diseases caused by plant pathogens that produce DSF.

Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children.

PubMed

Gupta, Vineeta; Kumar, Sushil; Sonowal, Rimjhim; Singh, Surya K

2017-04-01

The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease. IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009. Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; P<0.001). IL-8 levels were also significantly elevated in patients compared with controls (15.58±18.0 vs. 1.85±0.95; P<0.001). IL levels were also assessed in relation to severity of the disease. Levels were the highest in patients with very severe aplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non-severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy. High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.

The increased severity in patients presenting to hospital with diarrhea in Dhaka, Bangladesh since the emergence of the hybrid strain of Vibrio cholerae O1 is not unique to cholera patients.

PubMed

Chowdhury, Fahima; Kuchta, Alison; Khan, Ashraful Islam; Faruque, A S G; Calderwood, Stephen B; Ryan, Edward T; Qadri, Firdausi

2015-11-01

A hybrid strain of Vibrio cholerae O1 El Tor that expresses a classical cholera toxin (CT) emerged in 2001. This hybrid variant rapidly replaced the previous El Tor strain around the world. The global emergence of this variant coincided with anecdotal reports that cholera patients were presenting with more severe dehydration and disease in many locations. A comparison was made of the severity of disease before and after the emergence of the hybrid strain in cholera patients attending an icddr,b hospital in Dhaka, Bangladesh. It was found that cholera patients presented with more severe dehydration and severe disease in the later period. However, this was also true for all non-cholera patients as well. In addition, in sub-analyses of patients who presented with rotavirus and enterotoxigenic Escherichia coli (ETEC), similar results were found. Comparing the two periods for differences in patient characteristics, nutritional status, vaccination status, and income, no plausible cause for patients presenting with more severe disease was identified in the later period. As a shift in severity for both cholera and non-cholera was observed, these results indicate that the altered El Tor strain cannot fully explain the difference in cholera severity before and after 2001. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Disease Knowledge, Illness Perceptions, and Quality of Life in Adolescents With Sickle Cell Disease: Is There a Link?

PubMed Central

Asnani, Monika Rani; Barton-Gooden, Antoinette; Grindley, Marlyn; Knight-Madden, Jennifer

2017-01-01

Disease knowledge, illness perceptions, and quality of life (QOL) were examined in 150 adolescents (mean age = 16.1 years, SD = 1.9; 49.3% males) with sickle cell disease (SCD). Females had higher knowledge (P = .004), lower QOL (P = .02), and perceived their illness to be more unpredictable (P = .03). Those with more severe disease perceived their illness to be unpredictable with worse outcomes. Those with higher knowledge scores perceived their illness to be chronic, made more sense of their illness, and perceived greater personal and treatment control. Final hierarchical regression model showed that secondary education as compared to primary education level (P < .001) was positively correlated whereas disease severity (P < .001), perceived unpredictability (P = .024), and negative emotions (P < .001) were negatively correlated with QOL. Health practitioners should assess adolescents’ illness perceptions and encouraging continuing schooling and addressing emotional/psychological problems could improve their QOL. PMID:29152543

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

PubMed

Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

2017-08-01

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Patterns of circulating corticosterone in a population of rattlesnakes afflicted with snake fungal disease: Stress hormones as a potential mediator of seasonal cycles in disease severity and outcomes

USGS Publications Warehouse

Lind, Craig M.; Moore, Ignacio T.; Akçay, Çağlar; Vernasco, Ben J.; Lorch, Jeffrey M.; Farrell, Terence M.

2018-01-01

Snake fungal disease (SFD) is an emerging threat to snake populations in the United States. Fungal pathogens are often associated with a physiological stress response mediated by the hypothalamo-pituitary-adrenal axis (HPA), and afflicted individuals may incur steep coping costs. The severity of SFD can vary seasonally; however, little is known regarding (1) how SFD infection relates to HPA activity and (2) how seasonal shifts in environment, life history, or HPA activity may interact to drive seasonal patterns of infection severity and outcomes. To test the hypothesis that SFD is associated with increased HPA activity and to identify potential environmental or physiological drivers of seasonal infection, we monitored baseline corticosterone, SFD infection severity, foraging success, body condition, and reproductive status in a field-active population of pigmy rattlesnakes. Both plasma corticosterone and the severity of clinical signs of SFD peaked in the winter. Corticosterone levels were also elevated in the fall before the seasonal rise in SFD severity. Severely symptomatic snakes were in low body condition and had elevated corticosterone levels compared to moderately infected and uninfected snakes. The monthly mean severity of SFD in the population was negatively related to population-wide estimates of body condition and temperature measured in the precedent month and positively correlated with corticosterone levels measured in the precedent month. Symptomatic females were less likely to enter reproductive bouts compared to asymptomatic females. We propose the hypothesis that the seasonal interplay among environment, host energetics, and HPA activity initiates trade-offs in the fall that drive the increase in SFD prevalence, symptom severity, and decline in condition observed in the population through winter.

Prioritization of orphan disease-causing genes using topological feature and GO similarity between proteins in interaction networks.

PubMed

Li, Min; Li, Qi; Ganegoda, Gamage Upeksha; Wang, JianXin; Wu, FangXiang; Pan, Yi

2014-11-01

Identification of disease-causing genes among a large number of candidates is a fundamental challenge in human disease studies. However, it is still time-consuming and laborious to determine the real disease-causing genes by biological experiments. With the advances of the high-throughput techniques, a large number of protein-protein interactions have been produced. Therefore, to address this issue, several methods based on protein interaction network have been proposed. In this paper, we propose a shortest path-based algorithm, named SPranker, to prioritize disease-causing genes in protein interaction networks. Considering the fact that diseases with similar phenotypes are generally caused by functionally related genes, we further propose an improved algorithm SPGOranker by integrating the semantic similarity of GO annotations. SPGOranker not only considers the topological similarity between protein pairs in a protein interaction network but also takes their functional similarity into account. The proposed algorithms SPranker and SPGOranker were applied to 1598 known orphan disease-causing genes from 172 orphan diseases and compared with three state-of-the-art approaches, ICN, VS and RWR. The experimental results show that SPranker and SPGOranker outperform ICN, VS, and RWR for the prioritization of orphan disease-causing genes. Importantly, for the case study of severe combined immunodeficiency, SPranker and SPGOranker predict several novel causal genes.

Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004-2006).

PubMed

Kogan, David A; Johnson, Lynelle R; Sturges, Beverly K; Jandrey, Karl E; Pollard, Rachel E

2008-12-01

To evaluate the number and types of underlying disorders detected in dogs with aspiration pneumonia and determine the survival rate among affected dogs. Retrospective case series. Animals-88 dogs with aspiration pneumonia. Medical records were reviewed to identify disease processes that could result in aspiration pneumonia. To assess outcome (ie, survival to discharge from the hospital or nonsurvival), dogs were grouped by the type and number of underlying disease processes. Duration of hospitalization and radiographic severity of disease were evaluated with regard to case outcome. As the cause of aspiration pneumonia, a single underlying disorder was identified in 60 of the 88 dogs; 2 or more diseases were identified in the remaining dogs. Esophageal disease (n = 35), vomiting (34), neurologic disorders (24), laryngeal disease (16), and postanesthetic aspiration (12) were identified most commonly. Overall, 68 dogs survived to discharge from the hospital (survival rate, 77%). Survival rates were comparable among dogs regardless of the underlying cause of aspiration pneumonia. Radiographic severity of disease and duration of hospitalization did not influence survival. Among these study dogs, aspiration pneumonia was associated with a high survival rate. The presence of more than 1 underlying disease associated with aspiration pneumonia did not adversely impact survival rate. Interestingly, radiographic severity of disease and duration of hospitalization were not associated with overall survival rate.

A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD)

PubMed Central

Petek, Lisa M.; Rickard, Amanda M.; Budech, Christopher; Poliachik, Sandra L.; Shaw, Dennis; Ferguson, Mark R.; Tawil, Rabi; Friedman, Seth D.; Miller, Daniel G.

2016-01-01

Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value ≤ .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression. PMID:27185459

Relative disease susceptibility and clostridial toxin antibody responses in three commercial broiler lines coinfected with Clostridium perfringens and Eimeria maxima using an experimental model of necrotic enteritis.

PubMed

Jang, Seung I; Lillehoj, Hyun S; Lee, Sung-Hyen; Lee, Kyung Woo; Lillehoj, Erik P; Hong, Yeong Ho; An, Dong-Jun; Jeoung, D Hye-Young; Chun, Ji-Eun

2013-09-01

Necrotic enteritis is an enteric disease of poultry resulting from infection by Clostridium perfringens with coinfection by Eimeria spp. constituting a major risk factor for disease pathogenesis. This study compared three commercial broiler chicken lines using an experimental model of necrotic enteritis. Day-old male Cobb, Ross, and Hubbard broilers were orally infected with viable C. perfringens and E. maxima and fed a high-protein diet to promote the development of experimental disease. Body weight loss, intestinal lesions, and serum antibody levels against alpha-toxin and necrotic enteritis B-like (NetB) toxin were measured as parameters of disease susceptibility and host immune response. Cobb chickens exhibited increased body weight loss compared with Ross and Hubbard breeds and greater gut lesion severity compared with Ross chickens. NetB antibody levels were greater in Cobb chickens compared with the Ross or Hubbard groups. These results suggest that Cobb chickens may be more susceptible to necrotic enteritis in the field compared with the Ross and Hubbard lines.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

PubMed

Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

2014-12-01

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of cocoa supplementation on hepatic steatosis, reactive oxygen species and LFABP in a rat model of NASH

PubMed Central

2011-01-01

Background Non alcoholic steatohepatitis is hypothesised to develop via a mechanism involving fat accumulation and oxidative stress. The current study aimed to investigate if an increase in oxidative stress was associated with changes in the expression of liver fatty acid binding protein in a rat model of non alcoholic steatohepatitis and whether cocoa supplementation attenuated those changes. Methods Female Sprague Dawley rats were fed a high fat control diet, a high fat methionine choline deficient diet, or one of four 12.5% cocoa supplementation regimes in combination with the high fat methionine choline deficient diet. Results Liver fatty acid binding protein mRNA and protein levels were reduced in the liver of animals with fatty liver disease when compared to controls. Increased hepatic fat content was accompanied by higher levels of oxidative stress in animals with fatty liver disease when compared to controls. An inverse association was found between the levels of hepatic liver fatty acid binding protein and the level of hepatic oxidative stress in fatty liver disease. Elevated NADPH oxidase protein levels were detected in the liver of animals with increased severity in inflammation and fibrosis. Cocoa supplementation was associated with partial attenuation of these pathological changes, although the severity of liver disease induced by the methionine choline deficient diet prevented complete reversal of any disease associated changes. Red blood cell glutathione was increased by cocoa supplementation, whereas liver glutathione was reduced by cocoa compared to methionine choline deficient diet fed animals. Conclusion These findings suggest a potential role for liver fatty acid binding protein and NADPH oxidase in the development of non alcoholic steatohepatitis. Furthermore, cocoa supplementation may have be of therapeutic benefit in less sever forms of NASH. PMID:22081873

Correlation of hyponatremia with hepatic encephalopathy and severity of liver disease.

PubMed

Qureshi, Muhammad Omar; Khokhar, Nasir; Saleem, Atif; Niazi, Tariq Khan

2014-02-01

To assess the frequency of low serum sodium levels and to correlate it with the severity of liver disease and hepatic encephalopathy (HE) in patients coming to the tertiary care hospital. Observational study. Shifa International Hospital, Islamabad, from January 2011 to January 2012. A total of 202 patients with hepatic encephalopathy and chronic liver disease had serum sodium measured. The HE was graded according to the West Haven classification (4 grades). Relationship of hyponatremia was correlated with severity grade of encephalopathy using Spearman rank correlation test. Out of 202 patients, 62 (30.7%) patients had serum sodium less than 130 meq/l. Out of 202, HE was present in 69 (34.15%) patients and out of these, 38 had grade III-IV HE and 31 had grade I - II HE. Out of 69 patients with HE 57 had sodium less than 135 (p < 0.001). Hyponatremia was a common feature in patients with cirrhosis and its severity increased with the severity of liver disease. The existence of serum sodium concentration < 135 mmol/L was associated with greater frequency of hepatic encephalopathy compared with patients with serum sodium concentration > 135 mmol/L.

The efficacy of three different mask styles on a PAP titration night.

PubMed

Ebben, Matthew R; Oyegbile, Temitayo; Pollak, Charles P

2012-06-01

This study compared the efficacy of three different masks, nasal pillows, nasal masks and full face (oronasal) masks, during a single night of titration with continuous positive airway pressure (CPAP). Fifty five subjects that included men (n=33) and women (n=22) were randomly assigned to one of three masks and underwent a routine titration with incremental CPAP applied through the different masks. CPAP applied through the nasal pillows and nasal mask was equally effective in treating mild, moderate, and severe sleep apnea. However, CPAP applied through the oronasal mask required a significantly higher pressure compared to nasal masks to treat moderately severe (2.8 cm of H(2)O ± 2.1 SD) and severe (6.0 cm of H(2)O ± 3.2 SD) obstructive sleep apnea. CPAP applied with either nasal mask was effective in treating mild, moderate, and severe sleep apnea. The oronasal mask required significantly higher pressures in subjects with moderate to severe disease. Therefore, when changing from a nasal to an oronasal mask, a repeat titration is required to ensure effective treatment of sleep apnea, especially in patients with moderate to severe disease. Copyright © 2012 Elsevier B.V. All rights reserved.

[Physical work capacity of ischemic heart disease patients with various types of hyperlipoproteinemias].

PubMed

Zadionchenko, V S; Kopalova, S M

1980-08-01

The results of ergometric examination of 316 patients with chronic coronary insufficiency and various types of hyperlipoproteinemia have shown a clear diminution of physical working capacity in patients with hyperlipidemia as compared to patients with hyperlipidemia as compared to patients in whom the lipid content is within normal values. Working capacity was most diminished in IIa and particularly IIb types of hyperlipoproteinemia; in type IV physical working capacity was not reduced. The effect of hyperlipoproteinemia is most significant in the mildest degree of coronary insufficiency, but reduces or vanishes completely with increasing severity of the disease. An inverse relationship has been established between the value of physical working capacity and the level of cholesterol and beta-lipoproteins and a direct relationship in regard to NEFA concentration. Ergometry in patients with type II hyperlipoproteinemia showed that as compared to patients with normolipemia and type IV hyperlipoproteinemia an equal degree in the severity of the disease, the frequency and marked character of changes on the ECG increase; this evidences a more marked transitory myocardial ischemia.

Characteristics of past smokers.

PubMed

Kato, I; Tominaga, S; Suzuki, T

1989-06-01

We studied characteristics of past smokers according to the duration of cessation of smoking based on data from a population-based survey. Lifestyle, prevalences of various symptoms and diseases and other factors were compared among current smokers (8507 males and 2012 females), past smokers (4423 males and 684 females) and non-smokers (2431 males and 12,859 females) aged 40 years and over. Compared to current smokers, past smokers consumed more bread, milk, vegetables, fruit and black tea, and less rice, pickles, instant noodles, coffee and alcohol, had lower prevalences of cough, sputum and anorexia, participated more in cancer screening tests, weighed more, included more professional and administrative workers and had more non-smoking spouses. These characteristics resembled those of non-smokers. But past smokers had high prevalences of several cardiovascular and respiratory diseases compared to current smokers. Daily intake of coffee was inversely associated and daily intakes of fruit and milk were positively associated with the duration of abstinence from smoking after adjusting for other factors in both sexes. These results suggest that lifestyle of past smokers may contribute to risk reduction for several diseases.

Racial/Ethnic and County-level Disparity in Inpatient Utilization among Hawai'i Medicaid Population.

PubMed

Siriwardhana, Chathura; Lim, Eunjung; Aggarwal, Lovedhi; Davis, James; Hixon, Allen; Chen, John J

2018-05-01

We investigated racial/ethnic and county-level disparities in inpatient utilization for 15 clinical conditions among Hawaii's Medicaid population. The study was conducted using inpatient claims data from more than 200,000 Hawai'i Medicaid beneficiaries, reported in the year 2010. The analysis was performed by stratifying the Medicaid population into three age groups: children and adolescent group (1-20 years), adult group (21-64 years), and elderly group (65 years and above). Among the differences found, Asians had a low probability of inpatient admissions compared to Whites for many disease categories, while Native Hawaiian/Pacific Islanders had higher probabilities than Whites, across all age groups. Pediatric and adult groups from Hawai'i County (Big Island) had lower probabilities for inpatient admissions compared to Honolulu County (O'ahu) for most disease conditions, but higher probabilities were observed for several conditions in the elderly group. Notably, the elderly population residing on Kaua'i County (Kaua'i and Ni'ihau islands) had substantially increased odds of hospital admissions for several disease conditions, compared to Honolulu.

Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity.

PubMed

Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda

2013-10-01

Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

Importance of cutaneous silent period in fibromyalgia and its relationship with disease characteristics, psychological disorders and quality of life of patients.

PubMed

Umay, Ebru; Ulas, Umit; Unlu, Ece; Akgun, Hakan; Cakci, Aytul; Odabasi, Zeki

2013-01-01

Cutaneous silent period (CSP) is an inhibitory spinal protective reflex and its afferents consist of A-delta nerve fibers. We aimed to evaluate patients with fibromyalgia (FM) and healthy controls to determine any differences between the groups in terms of CSP duration and latency, and if present, to determine whether there is any relationship with disease characteristics, psychological disorders and quality of life. Thirty-two patients with FM and 32 healthy volunteers were included in the study. The patient and control groups were compared in terms of CSP latency and duration in both upper and lower extremities. Disease characteristics, psychological disorders and quality of life of patients were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and Short Form-36 (SF-36). Patients with CSP measurements equal to or lower than those of the control group were compared with those with higher values than controls in terms of disease characteristics, psychological status and quality of life. Significantly prolonged CSP latencies in both upper and lower extremities were determined in patients compared to controls. We found that prolongation of CSP latency in the lower extremity is associated with disease severity and functional disability. CSP latencies in both upper and lower extremities in patients with FM are longer than in healthy volunteers. Moreover, prolongation of CSP latency in the lower extremity is associated with disease severity and physical functional disability.

Stress and serum TNF-alpha levels may predict disease outcome in patients with pemphigus: a preliminary study.

PubMed

Ragab, Nader; Abdallah, Marwa; El-Gohary, Eman; Elewa, Rana

2011-04-01

The aim of the current preliminary case-control study was to estimate the initial serum levels of tumor necrosis factor alpha (TNF-alpha) in case patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) and correlate them with history of stress, body surface area (BSA) affected, disease severity, and disease outcome. Ten PV and 4 PF case patients as well as 7 healthy matched controls had their serum levels of TNF-alpha measured by an enzyme-linked immunosorbent assay. Case patients were treated and followed up for 2 months. A statistically significant elevation in serum levels of TNF-alpha in PV case patients compared with controls and in PV case patients compared with PF case patients was detected (P < .05), with no significant difference between PF case patients and controls (P > .05). No significant correlation was detected between the serum levels of TNF-alpha and the BSA affected (P > .05). Four PV case patients had a bad disease outcome, of which 3 had severe emotional stress a month prior to the onset of the attack. All 4 showed significantly elevated initial serum levels of TNF-alpha compared with those who had a good disease outcome (P < .05). Emotional stress is a factor affecting prognosis of the disease. Pretreatment assessment of serum TNF-alpha levels in patients with pemphigus may be a guide to the expected prognosis and selection of the proper treatment regimen.

Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

PubMed Central

Ponce-Guarneros, Manuel; Mejía, Mayra; Juárez-Contreras, Pablo; Corona-Sánchez, Esther Guadalupe; Rodríguez-Hernández, Tania Marlen; Salazar-Páramo, Mario; Cardona-Muñoz, Ernesto German; Celis, Alfredo; González-Lopez, Laura

2015-01-01

Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD. PMID:26090479

Clinical experience with adalimumab in a multicenter Swiss cohort of patients with Crohn's disease.

PubMed

Nichita, Cristina; Stelle, Marc; Vavricka, Stephan; El-Wafa Ali, Abdou; Ballabeni, Pierluigi; de Saussure, Philippe; Straumann, Alex; Rogler, Gerhard; Michetti, Pierre

2010-01-01

Controlled clinical trials have demonstrated the efficacy and safety of adalimumab in patients with moderate-to-severe Crohn's disease (CD), but there is, however, only limited long-term experience with adalimumab in daily practice. To assess the long-term effectiveness and safety of adalimumab in a multicenter cohort of practice-based patients with moderate-to-severe CD. We retrospectively reviewed the charts of CD patients who received adalimumab over a 3-year period. Disease severity was scored using the Harvey-Bradshaw index (HBI). Remission was defined as an HBI of 3 points at evaluation compared to the baseline. Univariate logistic regression analysis was used to identify the predictive variables associated with response. The charts of 55 patients were reviewed; remission and response rates observed at weeks 4-6 were 52.7 and 83.6%, respectively. Remission was maintained at weeks 12, 24 and 52 in 89.6, 72.4 and 44.7% of patients, respectively. Remission and response rates were not influenced by smoking status, disease location or duration, the first month total dose, or previous infliximab therapy. The remission rate at weeks 4-6 was significantly higher in patients intolerant of infliximab as compared to those who lost response to this drug. Adalimumab was well tolerated overall. Adalimumab can be considered a suitable option in patients with moderate-to-severe CD, demonstrating sustained long-term effectiveness. Copyright (c) 2010 S. Karger AG, Basel.

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sibille, A.; Eng, C.M.; Kim, S.J.

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, andmore » severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.« less

At-Risk Screened Children with Celiac Disease are Comparable in Disease Severity and Dietary Adherence to Those Found because of Clinical Suspicion: A Large Cohort Study.

PubMed

Kivelä, Laura; Kaukinen, Katri; Huhtala, Heini; Lähdeaho, Marja-Leena; Mäki, Markku; Kurppa, Kalle

2017-04-01

To assess whether children at risk for celiac disease should be screened systematically by comparing their baseline and follow-up characteristics to patients detected because of clinical suspicion. Five hundred four children with celiac disease were divided into screen-detected (n = 145) and clinically detected cohorts (n = 359). The groups were compared for clinical, serologic, and histologic characteristics and laboratory values. Follow-up data regarding adherence and response to gluten-free diet were compared. Subgroup analyses were made between asymptomatic and symptomatic screen-detected patients. Of screen-detected patients, 51.8% had symptoms at diagnosis, although these were milder than in clinically detected children (P < .001). Anemia (7.1% vs 22.9%, P < .001) and poor growth (15.7% vs 36.9%, P < .001) were more common, and hemoglobin (126 g/l vs 124 g/l, P = .008) and albumin (41.0 g/l vs 38.0 g/l, P = .016) were lower in clinically detected patients. There were no differences in serology or histology between the groups. Screen-detected children had better dietary adherence (91.2% vs 83.2%, P = .047). The groups showed equal clinical response (97.5% vs 96.2%, P = .766) to the gluten-free diet. In subgroup analysis among screen-detected children, asymptomatic patients were older than symptomatic (9.0  vs 5.8 years of age, P = .007), but the groups were comparable in other variables. More than one-half of the screen-detected patients with celiac disease had symptoms unrecognized at diagnosis. The severity of histologic damage, antibody levels, dietary adherence, and response to treatment in screen-detected cases is comparable with those detected on a clinical basis. The results support active screening for celiac disease among at-risk children. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.

PubMed

Sumner, Charlotte J; Wee, Claribel D; Warsing, Leigh C; Choe, Dong W; Ng, Andrew S; Lutz, Cathleen; Wagner, Kathryn R

2009-09-01

There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-beta family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn(-/-)) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.

Fatigue: an important feature of late-onset Pompe disease.

PubMed

Hagemans, Marloes L C; van Schie, Sabine P M; Janssens, A Cecile J W; van Doorn, Pieter A; Reuser, Arnold J J; van der Ploeg, Ans T

2007-07-01

To investigate the prevalence and severity of fatigue in adult patients with Pompe disease. The Fatigue Severity Scale (FSS) was assessed in an international population of 225 adults with Pompe disease, a metabolic disorder presenting as a slowly progressive proximal myopathy. The FSS scores were compared to those of healthy controls and the relationship between the level of fatigue and other patient characteristics was investigated. The mean age of the participants was 47 (SD 13) years and the mean disease duration 11 (SD 8) years. 43% used a wheelchair and 46% had respiratory support, 29% needed both. 67% of the participants had a FSS score > or =5, indicating severe fatigue. The mean FSS score was 5.2 (SD 1.5), which was significantly higher than that of healthy controls (p < 0.001). Fatigue was not related to age, sex or disease duration. Patients who used a wheelchair or respiratory support were on average more fatigued than those who did not (p = 0.01). However, of the patients who did not use these aids, 59% also had a FSS score > or =5. FSS scores were highest among patients who reported a high frequency of sleep disorders, but patients who never experienced sleep difficulties were also fatigued (mean FSS score = 4.8). Fatigue is highly prevalent among both mildly and severely affected adult patients with Pompe disease. The FSS appears a useful tool in assessing fatigue in Pompe disease.

Hepatitis C virus adversely affects quality of life.

PubMed

Cillo, Umberto; Amodio, Piero; Ronco, Claudio; Soni, Sachin S; Zanus, Giacomo; Minazzato, Lina; Salari, Annalisa; Neri, Daniele; Bombonato, Giancarlo; Schiff, Sami; Bianco, Tonino

2011-01-01

Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. These results show a significant impact of HCV infection on health status and subjective satisfaction. Copyright © 2011 S. Karger AG, Basel.

Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

PubMed Central

Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

1996-01-01

OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

PubMed

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

Neonatal Pulmonary MRI of Bronchopulmonary Dysplasia Predicts Short-term Clinical Outcomes.

PubMed

Higano, Nara S; Spielberg, David R; Fleck, Robert J; Schapiro, Andrew H; Walkup, Laura L; Hahn, Andrew D; Tkach, Jean A; Kingma, Paul S; Merhar, Stephanie L; Fain, Sean B; Woods, Jason C

2018-05-23

Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current NICHD/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD-defined BPD disease severity and predict short-term respiratory outcomes. Forty-two neonates (20 severe BPD, 6 moderate, 7 mild, 9 non-BPD controls; 40±3 weeks post-menstrual age) underwent quiet-breathing structural pulmonary MRI (ultrashort echo-time and gradient echo) in a NICU-sited, neonatal-sized 1.5T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared to clinical severity and short-term respiratory outcomes. Outcomes were predicted using univariate and multivariable models including clinical data and scores. MRI scores significantly correlated with severities and predicted respiratory support at NICU discharge (P<0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support. Quiet-breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short-term outcomes more accurately than any individual standard clinical measure. Importantly, this non-ionizing technique can be implemented to phenotype disease and has potential to serially assess efficacy of individualized therapies.

Comparative Analysis of Serum Proteins from Patients with Severe and Mild EV-A71-induced HFMD using iTRAQ-Coupled LC-MS/MS Screening.

PubMed

Fan, Peihu; Chen, Wei; Yu, Pin; Bao, Linlin; Xu, Lili; Qin, Chuan

2017-12-01

This study was designed to provide a rationale for monitoring the development of severe hand, foot, and mouth disease (HFMD) and predicting the onset of this disease via global comparative analysis between patients with severe and mild HFMD. The authors collected serum from five groups: mild (E-M) and severe (E-S) EV-A71-induced HFMD; mild (NE-M) and severe (NE-S) non-EV-A71-induced HFMD; and healthy control subjects (CON). The authors then performed comparative analysis and identified specific differentially expressed proteins (DEPs) of E-S using isobaric mass tag (isobaric tags for relative and absolute quantitation, iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Moreover, The authors validated specific DEPs by multiple reaction monitoring (MRM). The authors identified 10 specific proteins that were significantly altered in E-S patients. Bioinformatics analysis revealed that most of these DEPs are primarily involved in the acute response to infection, which was common to all groups. More importantly, up-regulated proteins associated with neural injury were specifically identified in the E-S group. These findings conclude that severe HFMD symptoms may be caused by EV-A71 infection-mediated injury of the neural system and provide a reference for future research on the course and prognosis of severe HFMD. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

PubMed Central

2010-01-01

Background To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions. Methods Epidemiologic, observational, and descriptive study (EPIDEPOC study). Patients ≥ 40 years of age with stable COPD attending primary care settings were included. Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected. Results were compared between patients with or without associated heart disease. Results A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males. When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease. Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease. Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases. The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05. Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost. Conclusion Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. PMID:20167091

The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the Starship experience (2000-2010).

PubMed

Concannon, A; Rudge, S; Yan, J; Reed, P

2013-10-01

To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children. A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively. Thirty-two children were diagnosed with jSLE with an annual incidence of 0.52 per 100,000 per year. Compared with European children (0.31 per 100,000 per year) the incidence of jSLE was higher among Maori and Pacific (0.67 per 100,000 per year, p=0.06) and significantly higher among Asian children (1.17 per 100,000 per year, p=0.01). Compared with European children, Maori and Pacific children were more frequently diagnosed with lupus nephritis (80% vs 40%, p=0.09) and severe (WHO class 4 or 5) renal lesions (60% vs 40%, p=0.43) at presentation. Similarly, at any time during the study, lupus nephritis (100% vs 40%, p=0.001) and severe (WHO class 4 or 5) renal lesions (73.3% vs 40%, p=0.12) were more frequent among Maori and Pacific compared with European children. Furthermore, retrospective BILAG assessment of diagnostic disease severity demonstrated that Maori and Pacific children experienced the majority of severe "Category A" disease (56.8% vs 22.7%, p=0.17) which was predominantly renal (73.3% vs 40%, p=0.12) in nature. This is the first description of the incidence and clinical manifestations of jSLE in a cohort of New Zealand children. Although limited by the small numbers involved it confirmed anecdotal suspicions that the incidence of jSLE among Maori, Pacific and Asian children is higher than European children. Lupus nephritis is also more frequent and severe in Maori and Pacific children.

Occurrence of spontaneous periodontal disease in the SAMP1/YitFc murine model of Crohn disease.

PubMed

Pietropaoli, Davide; Del Pinto, Rita; Corridoni, Daniele; Rodriguez-Palacios, Alexander; Di Stefano, Gabriella; Monaco, Annalisa; Weinberg, Aaron; Cominelli, Fabio

2014-12-01

Oral involvement is often associated with inflammatory bowel disease (IBD). Recent evidence suggests a high incidence of periodontal disease in patients with Crohn disease (CD). To the best of the authors' knowledge, no animal model of IBD that displays associated periodontal disease was reported previously. The aim of this study is to investigate the occurrence and progression of periodontal disease in SAMP1/YitFc (SAMP) mice that spontaneously develop a CD-like ileitis. In addition, the temporal correlation between the onset and progression of periodontal disease and the onset of ileitis in SAMP mice was studied. At different time points, SAMP and parental AKR/J (AKR) control mice were sacrificed, and mandibles were prepared for stereomicroscopy and histology. Terminal ilea were collected for histologic assessment of inflammation score. Periodontal status, i.e., alveolar bone loss (ABL) and alveolar bone crest, was examined by stereomicroscopy and histomorphometry, respectively. ABL increased in both strains with age. SAMP mice showed greater ABL compared with AKR mice by 12 weeks of age, with maximal differences observed at 27 weeks of age. AKR control mice did not show the same severity of periodontal disease. Interestingly, a strong positive correlation was found between ileitis severity and ABL in SAMP mice, independent of age. The present results demonstrate the occurrence of periodontal disease in a mouse model of progressive CD-like ileitis. In addition, the severity of periodontitis strongly correlated with the severity of ileitis, independent of age, suggesting that common pathogenic mechanisms, such as abnormal immune response and dysbiosis, may be shared between these two phenotypes.

Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

PubMed

Saint-Laurent Thibault, Catherine; Özer Stillman, Ipek; Chen, Stephanie; Getsios, Denis; Proskorovsky, Irina; Hernandez, Luis; Dixit, Shailja

2015-01-01

This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

Relationships between blood levels of fat soluble vitamins and disease etiology and severity in adults awaiting liver transplantation.

PubMed

Abbott-Johnson, Winsome; Kerlin, Paul; Clague, Alan; Johnson, Helen; Cuneo, Ross

2011-09-01

Although malnutrition is common in liver disease, there are limited data on fat soluble vitamins in various diseases. The aims of this study were to: (i) determine fat soluble vitamin levels in patients assessed for liver transplantation; (ii) compare levels between different disease etiologies (hepatocellular and cholestatic) and between subgroups of hepatocellular disease; and (iii) assess the multivariate contribution to vitamin levels of etiology and various indicators of disease severity. This was a cross-sectional study of 107 inpatients awaiting liver transplantation, mean age 47 years. Biochemical parameters included plasma retinol, 25-hydroxycholecalciferol, and vitamin E. Biochemical (albumin, bilirubin and zinc) and clinical indicators (Child-Pugh and Model of End Stage Liver Disease [MELD] scores) of disease severity were determined. Deficiencies of retinol (< 1.0 µmol/L), 25-hydroxycholecalciferol (< 50 nmol/L) and vitamin E (< 11 µmol/L) were present in 75%, 66% and 3%, respectively, of patients. Concentrations of retinol and vitamin E were lower in hepatocellular than cholestatic disease but 25-hydroxycholecalciferol concentrations were similar. Child-Pugh score was higher in hepatocellular than cholestatic disease. Concentrations of retinol were lower in alcoholic liver disease (ALD) than hepatitis and Child-Pugh score was higher in ALD. For the whole group, levels of retinol, 25-hydroxycholecalciferol and vitamin E were negatively related to Child-Pugh score, MELD score and bilirubin, and positively related to albumin. When Child-Pugh scores were controlled for, retinol was lower in the hepatocellular group. There was a high prevalence of fat soluble vitamin deficiencies with vitamin levels being related to disease severity. Retinol was lower in the hepatocellular group. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

The predictive value of C-reactive protein (CRP) in acute pancreatitis - is interval change in CRP an additional indicator of severity?

PubMed

Stirling, Aaron D; Moran, Neil R; Kelly, Michael E; Ridgway, Paul F; Conlon, Kevin C

2017-10-01

Using revised Atlanta classification defined outcomes, we compare absolute values in C-reactive protein (CRP), with interval changes in CRP, for severity stratification in acute pancreatitis (AP). A retrospective study of all first incidence AP was conducted over a 5-year period. Interval change in CRP values from admission to day 1, 2 and 3 was compared against the absolute values. Receiver-operator characteristic (ROC) curve and likelihood ratios (LRs) were used to compare ability to predict severe and mild disease. 337 cases of first incidence AP were included in our analysis. ROC curve analysis demonstrated the second day as the most useful time for repeat CRP measurement. A CRP interval change >90 mg/dL at 48 h (+LR 2.15, -LR 0.26) was equivalent to an absolute value of >150 mg/dL within 48 h (+LR 2.32, -LR 0.25). The optimal cut-off for absolute CRP based on new, more stringent definition of severity was >190 mg/dL (+LR 2.72, -LR 0.24). Interval change in CRP is a comparable measure to absolute CRP in the prognostication of AP severity. This study suggests a rise of >90 mg/dL from admission or an absolute value of >190 mg/dL at 48 h predicts severe disease with the greatest accuracy. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Utility and accuracy of perceptual voice and speech distinctions in the diagnosis of Parkinson's disease, PSP and MSA-P.

PubMed

Miller, Nick; Nath, Uma; Noble, Emma; Burn, David

2017-06-01

To determine if perceptual speech measures distinguish people with Parkinson's disease (PD), multiple system atrophy with predominant parkinsonism (MSA-P) and progressive supranuclear palsy (PSP). Speech-language therapists blind to patient characteristics employed clinical rating scales to evaluate speech/voice in 24 people with clinically diagnosed PD, 17 with PSP and 9 with MSA-P, matched for disease duration (mean 4.9 years, standard deviation 2.2). No consistent intergroup differences appeared on specific speech/voice variables. People with PD were significantly less impaired on overall speech/voice severity. Analyses by severity suggested further investigation around laryngeal, resonance and fluency changes may characterize individual groups. MSA-P and PSP compared with PD were distinguished by severity of speech/voice deterioration, but individual speech/voice parameters failed to consistently differentiate groups.

Expression Levels of pvcrt-o and pvmdr-1 Are Associated with Chloroquine Resistance and Severe Plasmodium vivax Malaria in Patients of the Brazilian Amazon

PubMed Central

Melo, Gisely C.; Monteiro, Wuelton M.; Siqueira, André M.; Silva, Siuhelem R.; Magalhães, Belisa M. L.; Alencar, Aline C. C.; Kuehn, Andrea; Portillo, Hernando A. del.; Fernandez-Becerra, Carmen; Lacerda, Marcus V. G.

2014-01-01

Molecular markers associated with the increase of chloroquine resistance and disease severity in Plasmodium vivax are needed. The objective of this study was to evaluate the expression levels of pvcrt-o and pvmdr-1 genes in a group of patients presenting CQRPv and patients who developed severe complications triggered exclusively by P. vivax infection. Two different sets of patients were included to this comprehensive study performed in the Brazilian Amazon: 1) patients with clinically characterized chloroquine-resistant P. vivax compared with patients with susceptible parasites from in vivo studies and 2) patients with severe vivax malaria compared with patients without severity. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters genes, P. vivax chloroquine resistance transporter (pvcrt-o) and the P. vivax multidrug resistance transporter (pvmdr-1). Twelve chloroquine resistant cases and other 15 isolates from susceptible cases were included in the first set of patients. For the second set, seven patients with P. vivax-attributed severe and 10 mild manifestations were included. Parasites from patients with chloroquine resistance presented up to 6.1 (95% CI: 3.8–14.3) and 2.4 (95% CI: 0.53–9.1) fold increase in pvcrt-o and pvmdr-1 expression levels, respectively, compared to the susceptible group. Parasites from the severe vivax group had a 2.9 (95% CI: 1.1–8.3) and 4.9 (95% CI: 2.3–18.8) fold increase in pvcrt-o and pvmdr-1 expression levels as compared to the control group with mild disease. These findings suggest that chloroquine resistance and clinical severity in P. vivax infections are strongly associated with increased expression levels of the pvcrt-o and pvmdr-1 genes likely involved in chloroquine resistance. PMID:25157811

Prediction of significant conduction disease through noninvasive assessment of cardiac calcification.

PubMed

Mainigi, Sumeet K; Chebrolu, Lakshmi Hima Bindu; Romero-Corral, Abel; Mehta, Vinay; Machado, Rodolfo Rozindo; Konecny, Tomas; Pressman, Gregg S

2012-10-01

Cardiac calcification is associated with coronary artery disease, arrhythmias, conduction disease, and adverse cardiac events. Recently, we have described an echocardiographic-based global cardiac calcification scoring system. The objective of this study was to evaluate the severity of cardiac calcification in patients with permanent pacemakers as based on this scoring system. Patients with a pacemaker implanted within the 2-year study period with a previous echocardiogram were identified and underwent blinded global cardiac calcium scoring. These patients were compared to matched control patients without a pacemaker who also underwent calcium scoring. The study group consisted of 49 patients with pacemaker implantation who were compared to 100 matched control patients. The mean calcium score in the pacemaker group was 3.3 ± 2.9 versus 1.8 ± 2.0 (P = 0.006) in the control group. Univariate and multivariate analysis revealed glomerular filtration rate and calcium scoring to be significant predictors of the presence of a pacemaker. Echocardiographic-based calcium scoring correlates with the presence of severe conduction disease requiring a pacemaker. © 2012, Wiley Periodicals, Inc.

Antimicrobial activity of topical agents against Propionibacterium acnes: an in vitro study of clinical isolates from a hospital in Shanghai, China.

PubMed

Ma, Ying; Zhang, Nanxue; Wu, Shi; Huang, Haihui; Cao, Yanpei

2016-12-01

This study aimed to compare the antimicrobial activities of topical agents against Propionibacterium acnes isolated from patients admitted to a hospital in Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes were determined in accordance with the Clinical and Laboratory Standards Institute. Susceptibilities to clindamycin and erythromycin were compared in terms of gender, age, disease duration, previous treatment, and disease severity. A total of 69 P. acnes strains were isolated from 98 patients (70.41%). The susceptibility to triple antibiotic ointment (neomycin/bacitracin/polymyxin B) and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%, 49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and erythromycin was significantly affected by gender, previous treatment, and disease severity rather than by age and disease duration. Topical antibiotics should not be used separately for long-term therapy to avoid multiresistance. The use of topical antibiotics should be determined by clinicians on the basis of clinical conditions.

Declining functional connectivity and changing hub locations in Alzheimer's disease: an EEG study.

PubMed

Engels, Marjolein M A; Stam, Cornelis J; van der Flier, Wiesje M; Scheltens, Philip; de Waal, Hanneke; van Straaten, Elisabeth C W

2015-08-20

EEG studies have shown that patients with Alzheimer's disease (AD) have weaker functional connectivity than controls, especially in higher frequency bands. Furthermore, active regions seem more prone to AD pathology. How functional connectivity is affected in AD subgroups of disease severity and how network hubs (highly connected brain areas) change is not known. We compared AD patients with different disease severity and controls in terms of functional connections, hub strength and hub location. We studied routine 21-channel resting-state electroencephalography (EEG) of 318 AD patients (divided into tertiles based on disease severity: mild, moderate and severe AD) and 133 age-matched controls. Functional connectivity between EEG channels was estimated with the Phase Lag Index (PLI). From the PLI-based connectivity matrix, the minimum spanning tree (MST) was derived. For each node (EEG channel) in the MST, the betweenness centrality (BC) was computed, a measure to quantify the relative importance of a node within the network. Then we derived color-coded head plots based on BC values and calculated the center of mass (the exact middle had x and y values of 0). A shifting of the hub locations was defined as a shift of the center of mass on the y-axis across groups. Multivariate general linear models with PLI or BC values as dependent variables and the groups as continuous variables were used in the five conventional frequency bands. We found that functional connectivity decreases with increasing disease severity in the alpha band. All, except for posterior, regions showed increasing BC values with increasing disease severity. The center of mass shifted from posterior to more anterior regions with increasing disease severity in the higher frequency bands, indicating a loss of relative functional importance of the posterior brain regions. In conclusion, we observed decreasing functional connectivity in the posterior regions, together with a shifted hub location from posterior to central regions with increasing AD severity. Relative hub strength decreases in posterior regions while other regions show a relative rise with increasing AD severity, which is in accordance with the activity-dependent degeneration theory. Our results indicate that hubs are disproportionally affected in AD.

Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy.

PubMed

Sanahuja, Jordi; Alonso, Núria; Diez, Javier; Ortega, Emilio; Rubinat, Esther; Traveset, Alícia; Alcubierre, Núria; Betriu, Àngels; Castelblanco, Esmeralda; Hernández, Marta; Purroy, Francisco; Arcidiacono, Maria Vittoria; Jurjo, Carmen; Fernández, Elvira; Puig-Domingo, Manuel; Groop, Per-Henrik; Mauricio, Dídac

2016-09-01

We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina. © 2016 by the American Diabetes Association.

Relationship between symptom load of gastro-oesophageal reflux disease and health-related quality of life, work productivity, resource utilization and concomitant diseases: survey of a US cohort.

PubMed

Wahlqvist, P; Karlsson, M; Johnson, D; Carlsson, J; Bolge, S C; Wallander, M-A

2008-05-01

Analysis of the burden of gastro-oesophageal reflux disease (GERD) in relation to the severity and frequency of symptoms is essential to identify individuals and groups in whom targeted management is justified. To describe the relationship between symptoms of GERD and self-reported health-related quality of life (HRQL), work productivity, healthcare utilization and concomitant diseases. US respondents to the Internet-based 2004 National Health and Wellness Survey who had self-reported GERD (n = 10,028, mean age: 52 years, 58% female) were age- and gender-matched to a control group without GERD (n = 10,028). Respondents with GERD were classified according to symptom severity and frequency. HRQL and productivity were assessed using the Short-Form 8 survey (SF-8) and Work Productivity and Activity Impairment questionnaire, respectively. Symptom frequency increased with increasing symptom severity. Compared with controls, respondents with GERD had more concomitant diseases [mean difference (MD): 1.6], lower SF-8 physical and mental health scores (MD: 4.1 units and 3.1 units, respectively), increased absenteeism (MD: 0.9 h/week), reduced percent productivity at work (MD: 7.5%) and increased healthcare utilization. All tested variables deteriorated with increasing symptom severity and/or frequency. Increasing severity and frequency of GERD symptoms is associated with more concomitant diseases, lower HRQL, lower work productivity and increased healthcare utilization, suggesting that patients with moderate or severe GERD should receive targeted management with the most effective treatment strategies.

Prediction of Severe Disease in Children with Diarrhea in a Resource-Limited Setting

PubMed Central

Levine, Adam C.; Munyaneza, Richard M.; Glavis-Bloom, Justin; Redditt, Vanessa; Cockrell, Hannah C.; Kalimba, Bantu; Kabemba, Valentin; Musavuli, Juvenal; Gakwerere, Mathias; Umurungi, Jean Paul de Charles; Shah, Sachita P.; Drobac, Peter C.

2013-01-01

Objective To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting. Methods Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death. Results The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93). Conclusions While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings. PMID:24349271

Peach leaf curl disease shifts sugar metabolism in severely infected leaves from source to sink.

PubMed

Moscatello, Stefano; Proietti, Simona; Buonaurio, Roberto; Famiani, Franco; Raggi, Vittorio; Walker, Robert P; Battistelli, Alberto

2017-03-01

Peach leaf curl is a disease that affects the leaves of peach trees, and in severe cases all of the leaf can be similarly affected. This study investigated some effects of this disease on the metabolism of peach leaves in which all parts of the leaf were infected. These diseased leaves contained very little chlorophyll and performed little or no photosynthesis. Compared to uninfected leaves, diseased leaves possessed higher contents of fructose and especially glucose, but lowered contents of sucrose, sorbitol and especially starch. The activities of soluble acid invertase, neutral invertase, sorbitol dehydrogenase and sucrose synthase were all higher in diseased leaves, whereas, those of aldose-6-phosphate reductase and sucrose phosphate synthase were lower. The activities of hexokinase and fructokinase were little changed. In addition, immunblots showed that the contents of Rubisco and ADP-glucose phosphorylase were reduced in diseased leaves, whereas, the content of phosphoenolpyruvate carboxylase was increased. The results show that certain aspects of the metabolism of diseased leaves are similar to immature sink leaves. That is photosynthetic function is reduced, the leaf imports rather than exports sugars, and the contents of non-structural carbohydrates and enzymes involved in their metabolism are similar to sink leaves. Further, the effects of peach leaf curl on the metabolism of peach leaves are comparable to the effects of some other diseases on the metabolism of photosynthetic organs of other plant species. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

PubMed

Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K

2016-09-28

Background and Aims: Patatin-like phospholipase domain protein 3 ( PNPLA3 ) polymorphisms ( rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

Clinical spectrum of Castleman disease–associated neuropathy

PubMed Central

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay

2016-01-01

Objective: To define the peripheral neuropathy phenotypes associated with Castleman disease. Methods: We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. Results: There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. Conclusion: There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. PMID:27807187

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population.

PubMed

Fattah, Shaimaa A; Ghattas, Maivel H; Saleh, Samy M; Abo-Elmatty, Dina M

2018-01-01

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects ( P  = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.

Socioeconomic impact of osteoarthritis in Hong Kong: utilization of health and social services, and direct and indirect costs.

PubMed

Woo, Jean; Lau, Edith; Lau, Chak Sing; Lee, Polly; Zhang, James; Kwok, Timothy; Chan, Cynthia; Chiu, P; Chan, Kai Ming; Chan, A; Lam, D

2003-08-15

To determine the direct and indirect cost of osteoarthritis (OA) according to disease severity, and to estimate the total cost of the disease in Hong Kong. This study is a retrospective, cross-sectional, nonrandom, cohort design, with subjects stratified according to disease severity based on functional limitation and the presence or absence of joint prosthesis. Subjects were recruited from primary care, geriatric medicine, rheumatology, and orthopedic clinics. There were 219 patients in the mild disease category, 290 patients in the severe category, and 65 patients with joint replacement. A questionnaire gathered information on demographic and socioeconomic characteristics, function limitation, use of health and social services, and effect on occupation and living arrangements over the previous 12 months. Costs were calculated as direct and indirect. Low education and socioeconomic class were associated with more severe disease. OA affected family or close relationships in 44%. The average cost incurred as a result of side effects of medication is similar to the average cost of medication itself. Excluding joint replacement, the direct costs ranged from Hong Kong (HK) dollar $11,690 to $40,180 per person per year and indirect costs, HK $3,300-$6,640. The direct costs are comparable to those reported in Western countries; however, the ratio of direct to indirect costs is much higher than 1, in contrast to the greater indirect versus direct costs reported in whites. The total cost expressed as a percentage of gross national product is also much lower in Hong Kong. The socioeconomic impact of OA in the Hong Kong population is comparable to Western countries, but the economic burden is largely placed on the government, with patients having relatively low out-of-pocket expenditures.

[Six-minute-walk test and maximum exercise test in cycloergometer in chronic obstructive pulmonary disease. Are the physiological demands equivalent?].

PubMed

Díaz, Orlando; Morales, Arturo; Osses, Rodrigo; Klaassen, Julieta; Lisboa, Carmen; Saldías, Fernando

2010-06-01

The physiological load imposed by the six minute walk test (SMWT) in chronic obstructive pulmonary disease (COPD) patients come from small studies where the influence of disease severity has not been assessed. The aim of the present study was to compare the SMWT with an incremental cardiopulmonary exercise test (CPET) in patients classified by disease severity according to FEV(1) (cutoff 50% predicted). Eighty-one COPD patients (53 with FEV(1) > or =50%) performed both tests on two consecutive days. Oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), minute ventilation (V(E)), heart rate (HR) and pulse oximetry (SpO(2)) were measured during SMWT and CPET using portable equipment. Dyspnea and leg fatigue were measured with the Borg scale. In both groups, walking speed was constant during the SMWT and VO(2) showed a plateau after the 3rd minute. When comparing SMWT (6th min) and peak CPET, patients with FEV(1) > or =50% showed a greater VO(2), but lower values of VCO(2),V(E), HR, dyspnea, leg fatigue, and SpO(2) during walking. In contrast, in those with FEV(1) <50% predicted values were similar. Distance walked during the SMWT strongly correlated with VO(2) at peak CPET (r=0.78; P=0.0001). The SMWT is a constant load exercise in COPD patients, regardless of disease severity. It imposes high metabolic, ventilatory and cardiovascular requirements, which were closer to those of CPET in severe COPD. These findings may explain the close correlation between distance walked and peak CPET VO(2). 2009 SEPAR. Published by Elsevier Espana. All rights reserved.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Comparative evaluation of serum C-reactive protein levels in chronic and aggressive periodontitis patients and association with periodontal disease severity.

PubMed

Goyal, Lata; Bey, Afshan; Gupta, N D; Sharma, Vivek Kumar

2014-10-01

C-reactive protein (CRP) is an acute-phase reactant and has been proved to be a significant predictor of future cardiovascular events. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. However, most of the studies have focused on chronic periodontitis and very few studies are done in patients with aggressive periodontitis. The aim of this study was to determine and compare the relative levels of serum CRP in aggressive and chronic periodontitis patients. A total of 75 systemically healthy subjects were divided into three groups: Group I, nonperiodontitis subjects; group II, chronic generalized periodontitis patients and group III, generalized aggressive periodontitis patients. All participants were subjected to quantitative CRP analysis using enzyme-linked immunosorbent assay. Mean CRP levels were significantly greater in both group II and III as compared to group I and group III having greater level than group II. Furthermore, CRP levels positively correlated with the amount of periodontal destruction as measured by probing depth and clinical attachment loss. The present study indicates a positive correlation between CRP and periodontal disease severity with particular concern in younger individuals that could be a possible underlying pathway in the association between periodontal disease and the observed higher risk for cardiovascular disease in periodontitis patients.

Clinical endpoints in the controlled human challenge model for Shigella: A call for standardization and the development of a disease severity score

PubMed Central

Lynen, Amanda; Riddle, Mark S.; Talaat, Kawsar; Sack, David; Gutiérrez, Ramiro L.; McKenzie, Robin; DeNearing, Barbara; Feijoo, Brittany; Kaminski, Robert W.; Taylor, David N.; Kirkpatrick, Beth D.; Bourgeois, A. Louis

2018-01-01

Background Since 1946 the controlled human infection model (CHIM) for Shigella has been used to improve understanding of disease pathogenesis, describe clinical and immunologic responses to infection and as a tool for vaccine development. As the frequency and intent for use in vaccine comparisons increases, standardization of the primary endpoint definition is necessary. Methods Subject-level data were obtained from previously conducted experimental Shigella CHIM studies. Signs and symptoms severity were categorized consistently across all studies. Sign and symptom correlations were estimated and univariate models were utilized to describe the association between stool output and other Shigella-attributable signs and symptoms. Multiple correspondence and hierarchical clustering analyses were performed to describe the co-occurrence of signs and symptoms. A disease score is proposed based on the co-occurrence of these events. Results Data were obtained on 54 subjects receiving 800 to 2000 colony forming units (cfu) of S. flexneri. The median maximum 24 hour stool output was 514 ml (IQR: 300, 998 ml) with a median frequency of 6 (IQR: 4, 9). Subjects reported abdominal pain or cramps (81.5%), headache (66.7%) and anorexia (64.8%), 50.0% had a fever and 27.8% had gross blood in multiple loose stools. Multiple correspondence analyses highlighted co-occurrence of symptoms based on severity. A 3-parameter disease severity score predicted shigellosis endpoints and better differentiated disease spectrum. Conclusion Dichotomous endpoints for Shigella CHIM fail to fully account for disease variability. An ordinal disease score characterizing the breadth of disease severity may enable a better characterization of shigellosis and can decrease sample size requirements. Furthermore, the disease severity score may be a useful tool for portfolio management by enabling prioritization across vaccine candidates with comparable efficacy estimates using dichotomous endpoints. PMID:29590182

Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease.

PubMed

Ilus, T; Kaukinen, K; Virta, L J; Huhtala, H; Mäki, M; Kurppa, K; Heikkinen, M; Heikura, M; Hirsi, E; Jantunen, K; Moilanen, V; Nielsen, C; Puhto, M; Pölkki, H; Vihriälä, I; Collin, P

2014-02-01

Refractory coeliac disease (RCD) is thought to be a rare disorder, but the accurate prevalence is unknown. We aimed to identify the prevalence of and the risk factors for developing RCD in a Finnish population where the clinical detection rate of coeliac disease is high. The study involved 11 hospital districts in Finland where the number of treated RCD patients (n = 44), clinically diagnosed coeliac disease patients (n = 12 243) and adult inhabitants (n = 1.7 million) was known. Clinical characteristics at diagnosis of coeliac disease between the RCD patients and patients with uncomplicated disease were compared. The prevalence of RCD was 0.31% among diagnosed coeliac disease patients and 0.002% in the general population. Of the enrolled 44 RCD patients, 68% had type I and 23% type II; in 9% the type was undetermined. Comparing 886 patients with uncomplicated coeliac disease with these 44 patients that developed RCD later in life, the latter were significantly older (median 56 vs 44 years, P < 0.001), more often males (41% vs. 24%, P = 0.012) and seronegative (30% vs. 5%, P < 0.001) at the diagnosis of coeliac disease. Patients with evolving RCD had more severe symptoms at the diagnosis of coeliac disease, including weight loss in 36% (vs. 16%, P = 0.001) and diarrhoea in 54% (vs. 38%, P = 0.050). Refractory coeliac disease is very rare in the general population. Patients of male gender, older age, severe symptoms or seronegativity at the diagnosis of coeliac disease are at risk of future refractory coeliac disease and should be followed up carefully. © 2014 John Wiley & Sons Ltd.

Clinical and molecular genetic features of Hb H and AE Bart's diseases in central Thai children.

PubMed

Traivaree, Chanchai; Boonyawat, Boonchai; Monsereenusorn, Chalinee; Rujkijyanont, Piya; Photia, Apichat

2018-01-01

α-Thalassemia, one of the major thalassemia types in Thailand, is caused by either deletion or non-deletional mutation of one or both α-globin genes. Inactivation of three α-globin genes causes hemoglobin H (Hb H) disease, and the combination of Hb H disease with heterozygous hemoglobin E (Hb E) results in AE Bart's disease. This study aimed to characterize the clinical and hematological manifestations of 76 pediatric patients with Hb H and AE Bart's diseases treated at Phramongkutklao Hospital, a tertiary care center for thalassemia patients in central Thailand. Seventy-six unrelated pediatric patients, 58 patients with Hb H disease and 18 patients with AE Bart's disease, were enrolled in this study. Their clinical presentations, transfusion requirement, laboratory findings, and mutation analysis were retrospectively reviewed and analyzed. A total of 76 pediatric patients with Hb H and AE Bart's diseases who mainly lived in central Thailand were included in this study. The clinical severities of patients with non-deletional mutations were more severe than those with deletional mutations. Eighty-six percent of patients with non-deletional AE Bart's disease required more blood transfusion compared to 12.5% of patients with deletional AE Bart's disease. Non-deletional AE Bart's disease also had a history of urgent blood transfusion with the average of 6±0.9 times compared to 1±0.3 times in patients with deletional Hb H disease. The difference was statistically significant. This study revealed the differences in clinical spectrum between patients with Hb H disease and those with AE Bart's disease in central Thailand. The differentiation of α-thalassemia is essential for appropriate management of patients. The molecular diagnosis is useful for diagnostic confirmation and genotype-phenotype correlation.

Ethnicity Modifies Associations between Cardiovascular Risk Factors and Disease Severity in Parallel Dutch and Singapore Coronary Cohorts

PubMed Central

Gijsberts, Crystel M.; Seneviratna, Aruni; de Carvalho, Leonardo P.; den Ruijter, Hester M.; Vidanapthirana, Puwalani; Sorokin, Vitaly; Stella, Pieter; Agostoni, Pierfrancesco; Asselbergs, Folkert W.; Richards, A. Mark; Low, Adrian F.; Lee, Chi-Hang; Tan, Huay Cheem; Hoefer, Imo E.; Pasterkamp, Gerard; de Kleijn, Dominique P. V.; Chan, Mark Y.

2015-01-01

Background In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world’s most populous ethnicities: Whites, Chinese, Indians and Malays. Methods The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. Results We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1–1.7], p = 0.008) and Malay (OR 1.9 [1.4–2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. Conclusion In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality. PMID:26147693

Genetic diversity of Schistosoma haematobium parasite IS NOT associated with severity of disease in an endemic area in Sudan.

PubMed

Gasmelseed, Nagla; Karamino, Nhashal E; Abdelwahed, Mohammed O; Hamdoun, Anas O; Elmadani, Ahmed E

2014-08-27

Over 650 million people globally are at risk of schistosomiasis infection, while more than 200 million people are infected of which the higher disease rates occur in children. Eighty three students between 6-20 years (mean 12.45 ± 3.2) from Quran School for boys in Radwan village, Gezira state were recruited to investigate for the relationship between the genetic diversity of Schistosoma haematobium strains and the severity of the disease. Schistosoma haematobium infection was detected by filtration of urine. Ultrasonography was done on each study subject, while PCR technique was used for genotyping via random amplified polymorphic DNA (RAPD) with A01, A02, A12, Y20 and A13 primers. A01 primer gave three different genotypes (A01-1, A01-2 and A01-3). About 54.2% (45/83) were S. haematobium egg positive by urine filtration. On assessment of the upper and lower urinary tract by ultrasound technique, 61.4% (51/83) were positiveand73.3% (60/83) samples were PCR positive. No significant difference was found when comparing the three different genotypes with severity of the disease. This study concludes that no association was found between the different genotypes of S.haemtobium and the severity of the disease. Examination of more samples from different areas to identify any possible differences between the parasites genes and disease severity was recommended.

Depression, insight, and personality changes in Alzheimer's disease and vascular dementia.

PubMed

Verhey, F R; Ponds, R W; Rozendaal, N; Jolles, J

1995-01-01

Although it is generally believed that depression, retained insight, and preserved personality occur more frequently in vascular dementia than in Alzheimer's disease, there is little empiric evidence for this presumption. Most studies on this subject have been carried out with severely demented inpatients, and confounding factors such as age, sex, and severity of dementia have not been sufficiently taken into account. We compared 48 patients with relatively mild vascular dementia with 48 patients with Alzheimer's disease, matched for age, sex, and stage of dementia, to investigate if depression, lack of insight, and personality changes were related to the cause of dementia. The two groups did not differ regarding the incidence of major depression, the mean depression score, the awareness score, or the sum of scores on the items of the Blessed Dementia Scale concerning personality changes. We conclude that depression, lack of insight, and personality changes do not favor an etiology of vascular dementia over that of Alzheimer's disease. The present findings underscore the notion that the severity of the dementia should be considered in studies on the differences between vascular dementia and Alzheimer's disease.

Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre

PubMed Central

Toledo, Jon B.; Arnold, Steven E.; Raible, Kevin; Brettschneider, Johannes; Xie, Sharon X.; Grossman, Murray; Monsell, Sarah E.; Kukull, Walter A.

2013-01-01

Cerebrovascular disease and vascular risk factors are associated with Alzheimer’s disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer’s Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer’s disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 ‘unremarkable brain’ cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer’s disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer’s disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer’s disease than in other neurodegenerative disorders, especially in younger subjects, and lowers the threshold for dementia due to Alzheimer’s disease and α-synucleinopathies, which suggests that these disorders should be targeted by treatments for cerebrovascular disease. PMID:23842566

Dengue Disease Risk Mental Models in the City of Dhaka, Bangladesh: Juxtapositions and Gaps Between the Public and Experts.

PubMed

Dhar-Chowdhury, Parnali; Haque, C Emdad; Driedger, S Michelle

2016-05-01

Worldwide, more than 50 million cases of dengue fever are reported every year in at least 124 countries, and it is estimated that approximately 2.5 billion people are at risk for dengue infection. In Bangladesh, the recurrence of dengue has become a growing public health threat. Notably, knowledge and perceptions of dengue disease risk, particularly among the public, are not well understood. Recognizing the importance of assessing risk perception, we adopted a comparative approach to examine a generic methodology to assess diverse sets of beliefs related to dengue disease risk. Our study mapped existing knowledge structures regarding the risk associated with dengue virus, its vector (Aedes mosquitoes), water container use, and human activities in the city of Dhaka, Bangladesh. "Public mental models" were developed from interviews and focus group discussions with diverse community groups; "expert mental models" were formulated based on open-ended discussions with experts in the pertinent fields. A comparative assessment of the public's and experts' knowledge and perception of dengue disease risk has revealed significant gaps in the perception of: (a) disease risk indicators and measurements; (b) disease severity; (c) control of disease spread; and (d) the institutions responsible for intervention. This assessment further identifies misconceptions in public perception regarding: (a) causes of dengue disease; (b) dengue disease symptoms; (c) dengue disease severity; (d) dengue vector ecology; and (e) dengue disease transmission. Based on these results, recommendations are put forward for improving communication of dengue risk and practicing local community engagement and knowledge enhancement in Bangladesh. © 2015 Society for Risk Analysis.

Detection of Theileria parva in tissues of cattle undergoing severe East Coast fever disease show significant parasite DNA accumulation in the spleen.

PubMed

Olds, Cassandra L; Paul, Tasha; Scoles, Glen A

2016-12-15

Infiltration and proliferation of Theileria parva infected lymphocytes in bovine host lymphoid organs is one of the hallmarks of T. parva infection. The relative abundance of parasites within infected host tissues, both lymphoid and non-lymphoid is however unknown. Using quantitative PCR, we have shown that significantly higher concentrations of T. parva DNA are detected in the spleens of cattle undergoing severe disease compared to other organs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage

PubMed Central

Cakmak, Erol; Duksal, Faysal; Altinkaya, Engin; Acibucu, Fettah; Dogan, Omer Tamer; Yonem, Ozlem; Yilmaz, Abdulkerim

2015-01-01

Background: Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis. Objectives: This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia. Patients and Methods: In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively. Results: One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner. Conclusions: We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe. PMID:26834793

The influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.

PubMed

Szewczyk-Krolikowski, Konrad; Tomlinson, Paul; Nithi, Kannan; Wade-Martins, Richard; Talbot, Kevin; Ben-Shlomo, Yoav; Hu, Michele T M

2014-01-01

Identifying factors influencing phenotypic heterogeneity in Parkinson's Disease is crucial for understanding variability in disease severity and progression. Age and gender are two most basic epidemiological characteristics, yet their effect on expression of PD symptoms is not fully defined. We aimed to delineate effects of age and gender on the phenotype in an incident cohort of PD patients and healthy controls from the Oxford Parkinson Disease Centre (OPDC). Clinical features, including demographic and medical characteristics and non-motor and motor symptoms, were analyzed in a group of PD patients within 3 years of diagnosis and a group of healthy controls from the OPDC cohort. Disease features were stratified according to age and compared between genders, controlling for effects of common covariates. 490 PD patients and 176 healthy controls were analyzed. Stratification by age showed increased disease severity with age on motor scales. Some non-motor features showed similar trend, including cognition and autonomic features. Comparison across genders highlighted a pattern of increased severity and greater symptom symmetricality in the face, neck and arms in men with women having more postural problems. Amongst the non-motor symptoms, men had more cognitive impairment, greater rate of REM behavior disorder (RBD), more orthostatic hypotension and sexual dysfunction. Age in PD is a strong factor contributing to disease severity even after controlling for the effect of disease duration. Gender-related motor phenotype can be defined by a vertical split into more symmetrical upper-body disease in men and disease dominated by postural symptoms in women. Copyright © 2013 Elsevier Ltd. All rights reserved.

Patterns of systemic lupus erythematosus expression in Europe.

PubMed

Cervera, R; Doria, A; Amoura, Z; Khamashta, M; Schneider, M; Guillemin, F; Maurel, F; Garofano, A; Roset, M; Perna, A; Murray, M; Schmitt, C; Boucot, I

2014-06-01

To analyse the differences in disease expression of European SLE patients based on gender, age at diagnosis, and ethnicity. A two-year, retrospective, multicentre, observational study was carried out in five countries (France, Germany, Italy, Spain and the UK). Patients' clinical manifestations including disease activity, organ involvement, organ damage and flares were analysed. Thirty-one centres enrolled 412 consecutive eligible patients (90.5% of women), with active disease, stratified by disease severity (half severe and half non-severe). Baseline characteristics included; mean (SD) age: 43.3 (13.6) years, SLE duration: 10.7 (8.0) years and age at disease diagnosis: 32.6 (13.0) years old. The mean (SD) SELENA-SLEDAI and SLICC/ACR scores were: 8.1 (6.7) and 0.82 (1.36), respectively. Over half of patients experienced flares (54.9%). The average number of annual flares was 1.01 (0.71) flares/year. In males compared to females, the renal system was more frequently active (53.8% vs 30.0%, p=0.002), the mean SLICC/ACR score was higher (1.15 vs 0.79, p=0.039) and the pulmonary system was more likely to be damaged (12.8% vs 3.8%, p=0.010). Furthermore, patients diagnosed at younger age displayed more renal system activity (young: 56.3% vs adult: 33.4% vs elder: 8.9%, p<0.001) and renal damage (25.0% vs 6.9% vs 2.2%, p=0.018) compared to the others. The annual number of flares (1.13 vs 1.05 vs 0.81 flares/year, p<0.0001), including the occurrence of severe flares (0.58 vs 0.51 vs 0.20, p<0.0001), was also higher in these patients. Conversely, greater organ damage was observed in patients diagnosed at an older age compared to the others. The mean SLICC/ACR score was higher (1.31 vs young: 0.88 and adult: 0.78, p<0.001) in patients diagnosed in the older age groups. The pulmonary (13.3% vs younger: 0% vs adult: 3.7%, p=0.030) and cardiovascular (17.8% vs younger: 0% vs adult: 2.9%, p<0.001) systems were more frequently damaged in these patients. Black African descents showed greater disease activity compared to Caucasian patients. They flared more often (77.1% vs 48.6%, p=0.001) and experienced a greater number of annual flares (1.57 vs 0.89 flares/year, p<0.0001), mainly more severe flares (0.89 vs 0.38/year, p<0.0001). They also were more likely to experience renal system damage. The study showed clearly two patient subsets. The disease was the most active in Black African descents, and this phenomenon has never been described before in continental Europe. The disease was also more active in patients diagnosed at a younger or adult. Greater disease damage was observed in males and in patients diagnosed at an older age. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of Disease Severity and Exercise Limitation on Exercise Training Intensity and Load and Health Benefits From Pulmonary Rehabilitation in Patients with COPD: AN EXPLORATORY STUDY.

PubMed

Huynh, Virginia C; Fuhr, Desi P; Byers, Bradley W; Selzler, Anne-Marie; Moore, Linn E; Stickland, Michael K

2018-04-11

Some patients with chronic obstructive pulmonary disease (COPD) fail to achieve health benefits with pulmonary rehabilitation (PR). Exercise intensity and load represent stimulus for adaptation but it is unclear whether inappropriate exercise intensity and/or load are affected by severity of COPD, which may affect health benefits. The purpose was to determine whether COPD severity and/or the severity of pulmonary limitation to exercise (PLE) impacted exercising intensity or load and whether resultant intensity/load affected health outcomes derived from PR. Patients with COPD (n = 58, age = 67 ± 7 y, forced expiratory volume in the first second of expiration [FEV1] % predicted = 52 ± 21%) were recruited upon referral to PR. Primary health outcomes evaluated were 6-min walk distance and St George's Respiratory Questionnaire. Patients were stratified for disease severity using Global Initiative for Obstructive Lung Disease (GOLD) staging and PLE severity by change in inspiratory capacity during exercise. Exercise intensity and load were calculated from daily exercise records. Participants achieved comparable training duration and load regardless of GOLD severity. Patients with more severe PLE achieved greater training duration (more severe: 546 ± 143 min., less severe: 451 ± 109 min., P = .036), and relative training load (more severe: 2200.8 ± 595.3 kcal, less severe: 1648.3 ± 597.8 kcal, P = .007). Greater overall training load was associated with greater improvements in 6-min walk distance (r = 0.24, P = .035). No significant relationships were observed between PLE, GOLD severity, training parameters, and St George's Respiratory Questionnaire response. Improvements in exercise tolerance can be explained by achieving greater training loads, demonstrating the importance of appropriate training load to maximize health outcomes in PR.

Proteomic Discovery and Development of a Multiplexed Targeted MRM-LC-MS/MS Assay for Urine Biomarkers of Extracellular Matrix Disruption in Mucopolysaccharidoses I, II, and VI.

PubMed

Heywood, Wendy E; Camuzeaux, Stephane; Doykov, Ivan; Patel, Nina; Preece, Rhian-Lauren; Footitt, Emma; Cleary, Maureen; Clayton, Peter; Grunewald, Stephanie; Abulhoul, Lara; Chakrapani, Anupam; Sebire, Neil J; Hindmarsh, Peter; de Koning, Tom J; Heales, Simon; Burke, Derek; Gissen, Paul; Mills, Kevin

2015-12-15

The mucopolysaccharidoses (MPS) are lysosomal storage disorders that result from defects in the catabolism of glycosaminoglycans. Impaired muscle, bone, and connective tissue are typical clinical features of MPS due to disruption of the extracellular matrix. Markers of MPS disease pathology are needed to determine disease severity and monitor effects of existing and emerging new treatments on disease mechanisms. Urine samples from a small cohort of MPS-I, -II, and -VI patients (n = 12) were analyzed using label-free quantative proteomics. Fifty-three proteins including many associated with extracellular matrix organization were differently expressed. A targeted multiplexed peptide MRM LC-MS/MS assay was used on a larger validation cohort of patient samples (MPS-I n = 18, MPS-II n = 12, MPS-VI n = 6, control n = 20). MPS-I and -II groups were further subdivided according to disease severity. None of the markers assessed were altered significantly in the mild disease groups compared to controls. β-galactosidase, a lysosomal protein, was elevated 3.6-5.7-fold significantly (p < 0.05) in all disease groups apart from mild MPS-I and -II. Collagen type Iα, fatty-acid-binding-protein 5, nidogen-1, cartilage oligomeric matrix protein, and insulin-like growth factor binding protein 7 concentrations were elevated in severe MPS I and II groups. Cartilage oligomeric matrix protein, insulin-like growth factor binding protein 7, and β-galactosidase were able to distinguish the severe neurological form of MPS-II from the milder non-neurological form. Protein Heg1 was significantly raised only in MPS-VI. This work describes the discovery of new biomarkers of MPS that represent disease pathology and allows the stratification of MPS-II patients according to disease severity.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

PubMed

Harari, S; Caminati, A; Albera, C; Vancheri, C; Poletti, V; Pesci, A; Luppi, F; Saltini, C; Agostini, C; Bargagli, E; Sebastiani, A; Sanduzzi, A; Giunta, V; Della Porta, R; Bandelli, G P; Puglisi, S; Tomassetti, S; Biffi, A; Cerri, S; Mari, A; Cinetto, F; Tirelli, F; Farinelli, G; Bocchino, M; Specchia, C; Confalonieri, M

2015-07-01

In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

PubMed

Gkourogianni, Alexandra; Sinaii, Ninet; Jackson, Sharon H; Karageorgiadis, Alexander S; Lyssikatos, Charalampos; Belyavskaya, Elena; Keil, Margaret F; Zilbermint, Mihail; Chittiboina, Prashant; Stratakis, Constantine A; Lodish, Maya B

2017-08-01

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children.

[Characteristics of cases hospitalized for severe pandemic (H1N1) 2009 in Catalonia].

PubMed

Godoy, Pere; Rodés, Anna; Alvarez, Josep; Camps, Neus; Barrabeig, Irene; Sala, María Rosa; Minguell, Sofía; Lafuente, Sarah; Pumarola, Tomás; Domínguez, Angela; Plasència, Antoni

2011-01-01

Influenza pandemics may cause more severe cases. The objective was to determine the characteristics of hospitalized severe cases of pandemic influenza in Catalonia and to study risk factors for admission to intensive care unit (ICU). A prospective epidemiologic study of new cases of pandemic influenza hospitalized by their severity between June 2009 and May 2010. Hospitals were asked to declare laboratory confirmed pandemic influenza cases that met the case specific case definition for severe case. A standardized epidemiological survey was conducted to collect information on demographics, clinical characteristics, risk factors, treatment and outcome. Differences between the cases in ICU compared to other severe cases were studied with the odds ratio (OR), which were adjusted using a logistic regression model. We detected total of 773 pandemic influenza (H1N1) 2009 severe cases; 465 (60.2%) of them had at least one risk factor and the most prevalent were: pregnancy 19 (13%), asthma 87 (12%), chronic obstructive pulmonary disease 87 (11.4%) and heart disease 80 (10.5%). Required admission to ICU 293 patients (37.9%). Factors associated with ICU admission were obesity BMI>40 (adjusted OR = 2.5, 95% CI 1.4-4.5) and chronic liver disease (adjusted OR = 2.3, 95% CI 1.1-4.8). This study confirms the high prevalence of pregnancy, chronic respiratory diseases, diabetes and obesity among pandemic influenza severe cases. Obesity acts as a risk factor for ICU admission and should therefore be considered as an indicator for influenza vaccination.

Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

PubMed

Peña-Sagredo, J L; Fariñas, M C; Perez-Zafrilla, B; Cruz-Valenciano, A; Crespo, M; Joven-Ibañez, B; Riera, E; Manero-Ruiz, F J; Chalmeta, I; Hernández, M V; Rodríguez-Gómez, M; Maíz, O; López, R; Cobo, T; Pita, J; Carmona, L; Gonzalez-Gay, M A

2009-01-01

The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

Self-reported pain intensity with the numeric reporting scale in adult dengue.

PubMed

Wong, Joshua G X; Gan, Victor C; Ng, Ee-Ling; Leo, Yee-Sin; Chan, Siew-Pang; Choo, Robin; Lye, David C

2014-01-01

Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients' day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient's progression to severe disease.

Comparative analysis of human tissue interactomes reveals factors leading to tissue-specific manifestation of hereditary diseases.

PubMed

Barshir, Ruth; Shwartz, Omer; Smoly, Ilan Y; Yeger-Lotem, Esti

2014-06-01

An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases, which are caused by genomic aberrations that are present in cells across the human body. Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis. We created an extensive resource of protein expression and interactions in 16 main human tissues, by integrating recent data of gene and protein expression across tissues with data of protein-protein interactions (PPIs). The resulting tissue interaction networks (interactomes) shared a large fraction of their proteins and PPIs, and only a small fraction of them were tissue-specific. Applying this resource to hereditary diseases, we first show that most of the disease-causing genes are widely expressed across tissues, yet, enigmatically, cause disease phenotypes in few tissues only. Upon testing for factors that could lead to tissue-specific vulnerability, we find that disease-causing genes tend to have elevated transcript levels and increased number of tissue-specific PPIs in their disease tissues compared to unaffected tissues. We demonstrate through several examples that these tissue-specific PPIs can highlight disease mechanisms, and thus, owing to their small number, provide a powerful filter for interrogating disease etiologies. As two thirds of the hereditary diseases are associated with these factors, comparative tissue analysis offers a meaningful and efficient framework for enhancing the understanding of the molecular basis of hereditary diseases.

Severe and moderate haemophilia A and B in US females.

PubMed

Di Michele, D M; Gibb, C; Lefkowitz, J M; Ni, Q; Gerber, L M; Ganguly, A

2014-03-01

Haemophilia A and B are rare X-lined hemorrhagic disorders that typically affect men. Women are usually asymptomatic carriers, but may be symptomatic and, rarely, also express severe (factor VIII (FVIII) or factor IX (FIX) <0.01 U mL(-1)) or moderately severe (FVIII/FIX 0.01-0.05 U mL(-1)) phenotypes. However, data on clinical manifestations, genotype and the psychosocial ramifications of illness in severely affected females remain anecdotal. A national multi-centre retrospective study was conducted to collect a comprehensive data set on affected US girls and women, and to compare clinical observations to previously published information on haemophilic males of comparable severity and mildly affected haemophilic females. Twenty-two severe/moderate haemophilia A/B subjects were characterized with respect to clinical manifestations and disease complications; genetic determinants of phenotypic severity; and health-related quality of life (HR-QoL). Clinical data were compared as previously indicated. Female patients were older than male patients at diagnosis, but similarly experienced joint haemorrhage, disease- and treatment-related complications and access to treatment. Gynaecological and obstetrical bleeding was unexpectedly infrequent. F8 or F9 mutations, accompanied by extremely skewed X-chromosome inactivation pattern (XIP), were primary determinants of severity. HR-QoL was diminished by arthropathy and viral infection. Using systematic case verification of participants in a national surveillance registry, this study elucidated the genetics, clinical phenotype and quality of life issues in female patients with severe/moderate haemophilia. An ongoing international case-controlled study will further evaluate these observations. Novel mechanistic questions are raised about the relationship between XIP and both age and tissue-specific FVIII and FIX expression. © 2014 John Wiley & Sons Ltd.

Neuropathology of dementia with Lewy bodies in advanced age: a comparison with Alzheimer disease.

PubMed

Ubhi, Kiren; Peng, Kevin; Lessig, Stephanie; Estrella, Jennilyn; Adame, Anthony; Galasko, Douglas; Salmon, David P; Hansen, Lawrence A; Kawas, Claudia H; Masliah, Eliezer

2010-11-26

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder of the aging population characterized by α-synuclein accumulation in cortical and subcortical regions. Although neuropathology in advanced age has been investigated in dementias such as Alzheimer Disease (AD), severity of the neuropathology in the oldest old with DLB remains uncharacterized. For this purpose we compared characteristics of DLB cases divided into three age groups 70-79, 80-89 and ≥ 90 years (oldest old). Neuropathological indicators and levels of synaptophysin were assessed and correlated with clinical measurements of cognition and dementia severity. These studies showed that frequency and severity of DLB was lower in 80-89 and ≥ 90 year cases compared to 70-79 year old group but cognitive impairment did not vary with age. The extent of AD neuropathology correlated with dementia severity only in the 70-79 year group, while synaptophysin immunoreactivity more strongly associated with dementia severity in the older age group in both DLB and AD. Taken together these results suggest that the oldest old with DLB might represent a distinct group. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

PubMed Central

da Fontoura Budaszewski, Renata; von Messling, Veronika

2016-01-01

Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

Low Platelet to White Blood Cell Ratio Indicates Poor Prognosis for Acute-On-Chronic Liver Failure.

PubMed

Jie, Yusheng; Gong, Jiao; Xiao, Cuicui; Zhu, Shuguang; Zhou, Wenying; Luo, Juan; Chong, Yutian; Hu, Bo

2018-01-01

Background. Platelet to white blood cell ratio (PWR) was an independent prognostic predictor for outcomes in some diseases. However, the prognostic role of PWR is still unclear in patients with hepatitis B related acute-on-chronic liver failure (ACLF). In this study, we evaluated the clinical performances of PWR in predicting prognosis in HBV-related ACLF. Methods. A total of 530 subjects were recruited, including 97 healthy controls and 433 with HBV-related ACLF. Liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing were performed at admission. Results . At baseline, PWR in patients with HBV-related ACLF (14.03 ± 7.17) was significantly decreased compared to those in healthy controls (39.16 ± 9.80). Reduced PWR values were clinically associated with the severity of liver disease and the increased mortality rate. Furthermore, PWR may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 0.660, 95% CI: 0.438-0.996, p = 0.048) as well as model for end-stage liver disease (MELD) score. Conclusions . The PWR values were markedly decreased in ACLF patients compared with healthy controls and associated with severe liver disease. Moreover, PWR was an independent prognostic indicator for the mortality rate in patients with ACLF. This investigation highlights that PWR comprised a useful biomarker for prediction of liver severity.

Transcriptional Response of Virus-Infected Cassava and Identification of Putative Sources of Resistance for Cassava Brown Streak Disease

PubMed Central

Maruthi, M. N.; Bouvaine, Sophie; Tufan, Hale A.; Mohammed, Ibrahim U.; Hillocks, Rory J.

2014-01-01

Cassava (Manihot esculenta) is a major food staple in sub-Saharan Africa, which is severely affected by cassava brown streak disease (CBSD). The aim of this study was to identify resistance for CBSD as well as to understand the mechanism of putative resistance for providing effective control for the disease. Three cassava varieties; Kaleso, Kiroba and Albert were inoculated with cassava brown streak viruses by grafting and also using the natural insect vector the whitefly, Bemisia tabaci. Kaleso expressed mild or no disease symptoms and supported low concentrations of viruses, which is a characteristic of resistant plants. In comparison, Kiroba expressed severe leaf but milder root symptoms, while Albert was susceptible with severe symptoms both on leaves and roots. Real-time PCR was used to estimate virus concentrations in cassava varieties. Virus quantities were higher in Kiroba and Albert compared to Kaleso. The Illumina RNA-sequencing was used to further understand the genetic basis of resistance. More than 700 genes were uniquely overexpressed in Kaleso in response to virus infection compared to Albert. Surprisingly, none of them were similar to known resistant gene orthologs. Some of the overexpressed genes, however, belonged to the hormone signalling pathways and secondary metabolites, both of which are linked to plant resistance. These genes should be further characterised before confirming their role in resistance to CBSD. PMID:24846209

Salivary pH: A diagnostic biomarker.

PubMed

Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

2013-07-01

Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

Severe Hemifacial Spasm is a Predictor of Severe Indentation and Facial Palsy after Microdecompression Surgery.

PubMed

Na, Boo Suk; Cho, Jin Whan; Park, Kwan; Kwon, Soonwook; Kim, Ye Sel; Kim, Ji Sun; Youn, Jinyoung

2018-04-27

Hemifacial spasm (HFS) is mostly caused by the compression of the facial nerve by cerebral vessels, but the significance of spasm severity remains unclear. We investigated the clinical significance of spasm severity in patients with HFS who underwent microvascular decompression (MVD). We enrolled 636 patients with HFS who underwent MVD between May 2010 and December 2013 at Samsung Medical Center (SMC), Seoul, Korea. Subjects were divided into two groups based on spasm severity: severe (SMC grade 3 or 4) and mild (SMC grade 1 or 2). We compared demographic, clinical, and surgical data between these two groups. The severe-spasm group was older and had a longer disease duration at the time of MVD compared to the mild-spasm group. Additionally, hypertension and diabetes mellitus were more common in the severe-spasm group than in the mild-spasm group. Regarding surgical findings, there were more patients with multiple offending vessels and more-severe indentations in the severe-spasm group than in the mild-spasm group. Even though the surgical outcomes did not differ, the incidence of delayed facial palsy after MVD was higher in the severe-spasm group than in the mild-spasm group. Logistic regression analysis showed that severe-spasm was correlated with longer disease duration, hypertension, severe indentation, multiple offending vessels, and delayed facial palsy after MVD. Spasm severity does not predict surgical outcomes, but it can be used as a marker of pathologic compression in MVD for HFS, and be considered as a predictor of delayed facial palsy after MVD. Copyright © 2018 Korean Neurological Association.

Quantitative analysis of formal caregivers' use of communication strategies while assisting individuals with moderate and severe Alzheimer's disease during oral care.

PubMed

Wilson, Rozanne; Rochon, Elizabeth; Mihailidis, Alex; Leonard, Carol

2013-01-01

This cross-sectional observational study examined formal caregivers' use of task-focused and social communication strategies while assisting individuals with moderate and severe Alzheimer's disease residing in a long-term care facility during a basic activity of daily living: toothbrushing. Thirteen formal caregiver-resident dyads were observed during a total of 78 separate toothbrushing sessions. All caregiver utterances occurring during the task were transcribed and coded for type of communication strategy utilizing a multidimensional observational coding scheme, which was developed a priori. Overall, the majority of residents, irrespective of disease severity, successfully completed toothbrushing with the support of caregiver assistance. Caregivers assisting residents with moderate and severe AD were found to use a variety of communication strategies, with task-focused strategies accounting for the majority of use. For the most part, the communicative strategies employed did not differ across disease severity. However, some differences were identified including the use of one proposition, paraphrased repetition, using the resident's name, and provision of full assistance, with these strategies being used more often when assisting individuals with severe AD. This study adds to the emerging literature supporting the use of specific communication strategies while assisting residents with AD during the completion of daily tasks. From reviewing this study, readers will be able to identify a variety of communication strategies, both task-focused and relational, that formal caregivers utilize while assisting residents with moderate and severe Alzheimer's disease (AD) during a basic activity of daily living. Furthermore, the reader will be able to distinguish between communication strategies that are optimal when assisting individuals with moderate AD as compared to assisting individuals with severe AD. Copyright © 2013 Elsevier Inc. All rights reserved.

Laparoscopic Surgical Treatment of Severe Obesity Combined with Gastroesophageal Reflux Disease: A Pilot Randomized Two-Arm Controlled Clinical Study

ERIC Educational Resources Information Center

Ospanov, Oral B.; Orekeshova, Akzhunis M.; Fursov, Roman A.; Yelemesov, Aset A.

2016-01-01

Obesity and gastroesophageal reflux disease (GERD) are serious medical, social, and economic problems of modern society. A pilot randomized two-arm controlled clinical study was conducted to compare laparoscopic plication of the greater gastric curvature combined with Nissen fundoplication (LFN+LGP) versus only Nissen fundoplication (LFN). The…

The role of colonic mast cells and myenteric plexitis in patients with diverticular disease.

PubMed

Bassotti, Gabrio; Villanacci, Vincenzo; Nascimbeni, Riccardo; Antonelli, Elisabetta; Cadei, Moris; Manenti, Stefania; Lorenzi, Luisa; Titi, Amin; Salerni, Bruno

2013-02-01

Gut mast cells represent an important cell population involved in intestinal homeostasis and inflammatory processes. However, their possible role has not to date been investigated in colonic diverticular disease. This study aims to evaluate colonic mast cells in patients undergoing surgery for diverticular disease. Surgical resection samples from 27 patients undergoing surgery for diverticular disease (12 emergency procedures for severe disease and 15 elective procedures) were evaluated. The number of mast cells was assessed in the various layers by means of a specific antibody (tryptase) and compared with those evaluated in ten controls. In patients with mast cells degranulation, double immunohistochemistry, also assessing nerve fibres, was carried out. In addition, the presence of myenteric plexitis was sought. Compared with controls, the number of mast cells in diverticular patients was significantly increased, both as an overall figure and in the various layers of the large bowel. In patients in whom mast cells degranulation was present, these were always closed to nerve fibres. No differences were found between the two subgroups of patients with respect to the number and distribution of mast cells; however, all patients undergoing emergency surgery (but none of those undergoing elective procedures) had myenteric plexitis, represented by lymphocytic infiltration in 67 % and eosinophilic infiltration in 33 % of cases. Patients with diverticular disease display an increase of mast cells in the large bowel. The presence of myenteric plexitis in those with complicated, severe disease, suggest that this could represent a histopathologic marker of more aggressive disease.

Tuberculosis at Raffic Hariri University Hospital (RHUH) during 10 years period 2005-2015, cross sectional, observational study.

PubMed

Zadeh, Catherina; Tayara, Loubna

2018-07-01

Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis. It represents, according to WHO, one of the most leading causes of death worldwide. 1 BACKGROUND: Based on our regional conditions, such as Syrian immigration, poor nutritional status, are contributors for the development of the disease. This was a retrospective analytical cross sectional study done to review all cases of tuberculosis newly diagnosed at RHUH during 10 years period (2005-2015). 128 TB labeled patients were retrieved. A standardized checklist was used to collect data. Patients were then classified as TB diseased and TB infected. The total number of TB suspected patients was 128 over 10 years which represents 1.77% of all patients admitted to the medical floor. Among these, the total number of PPD positive patients was 40.6% from our study population (2005-2015), 48% were TB infected and 52% had positive CXR. Among those with positive CXR, 41% were confirmed TB disease and 59% not confirmed TB disease. There was significant variation in evolution through years (2005-2015). By comparing the socio-demographic findings between TB disease, TB infection and non-TB group no statistical significance was found. Same analysis were repeated between TB infection and TB disease groups showed one significant association between age and TB disease vs. TB infection (p=0.034), where the younger population belongs to TB infected group (42%), while 50% of TB diseased group were older. As for scoring severity index, ANOVA in the three groups showed a significant association with a p value of 0.046. The TB diseased patients have the highest severity score index. TB disease is still present in Lebanon with fluctuating level with the highest peak found in 2013 explained by the influx of Syrian refugee population. Followed by a gradual drop in the following years. The younger population belongs to TB infected group, while TB disease patients had the most severe clinical course compared to TB infected and non TB patients. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Bronchiolitis obliterans and consumer exposure to butter-flavored microwave popcorn: a case series.

PubMed

Egilman, David S; Schilling, John Henry

2012-01-01

Respiratory exposure to diacetyl and diacetyl-containing flavorings used in butter-flavored microwave popcorn (BFMP) causes lung disease, including bronchiolitis obliterans (BO), in flavorings and popcorn manufacturing workers. However, there are no published reports of lung disease among BFMP consumers. We present a case series of three BFMP consumers with biopsy-confirmed BO. We review data relating to consumer exposures, estimate case exposures, and compare them to diacetyl-containing flavoring-exposed manufacturing workers with lung disease. These consumer cases' exposure levels are comparable to those that caused disease in workers. We were unable to identify any other exposures or diseases known or suspected to cause BO in these cases. BFMP poses a significant respiratory risk to consumers. Some manufacturers have substituted diacetyl with other alpha-diketones that are likely to pose a similar risk. Simple consumer practices such as cooling the popcorn bag would eliminate the risk of severe lung disease.

Association of Irisin and CRP Levels with the Radiographic Severity of Knee Osteoarthritis.

PubMed

Mao, Yongtao; Xu, Wei; Xie, Zonggang; Dong, Qirong

2016-02-01

Irisin, a recently identified myokine, is implicated in protecting mice from obesity. This study was designed to examine the relation of irisin levels in serum and synovial fluid (SF) with the radiographic severity of osteoarthritis (OA). Our study included 215 patients with knee OA. Irisin levels in serum and SF were evaluated using an enzyme-linked immunosorbent assay. The progression of OA was assessed using Kellgren-Lawrence grading system. Knee OA patients had lower serum irisin concentrations and increased serum C-reactive protein (CRP) levels compared with healthy controls. There were markedly decreased irisin levels in both the serum and the SF, as well as increased serum CRP levels of knee OA patients with Kellgren and Lawrence (KL) grade 4 compared with patients classified as KL grade 2 and 3. Furthermore, patients with KL grade 3 showed markedly reduced serum and SF levels of irisin, as well as increased serum CRP levels compared with patients classified as KL grade 2. Irisin levels in serum and SF of knee OA patients were negatively correlated with disease severity evaluated by KL grading criteria. Irisin levels in the serum and SF of knee OA patients were negatively correlated with disease severity evaluated by the radiographic KL grading criteria.

Severe respiratory illness associated with a nationwide outbreak of enterovirus D68 in the USA (2014): a descriptive epidemiological investigation

PubMed Central

Midgley, Claire M; Watson, John T; Nix, W Allan; Curns, Aaron T; Rogers, Shannon L; Brown, Betty A; Conover, Craig; Dominguez, Samuel R; Feikin, Daniel R; Gray, Samantha; Hassan, Ferdaus; Hoferka, Stacey; Jackson, Mary Anne; Johnson, Daniel; Leshem, Eyal; Miller, Lisa; Nichols, Janell Bezdek; Nyquist, Ann-Christine; Obringer, Emily; Patel, Ajanta; Patel, Megan; Rha, Brian; Schneider, Eileen; Schuster, Jennifer E; Selvarangan, Rangaraj; Seward, Jane F; Turabelidze, George; Oberste, M Steven; Pallansch, Mark A; Gerber, Susan I

2016-01-01

Summary Background Enterovirus D68 (EV-D68) has been infrequently reported historically, and is typically associated with isolated cases or small clusters of respiratory illness. Beginning in August, 2014, increases in severe respiratory illness associated with EV-D68 were reported across the USA. We aimed to describe the clinical, epidemiological, and laboratory features of this outbreak, and to better understand the role of EV-D68 in severe respiratory illness. Methods We collected regional syndromic surveillance data for epidemiological weeks 23 to 44, 2014, (June 1 to Nov 1, 2014) and hospital admissions data for epidemiological weeks 27 to 44, 2014, (June 29 to Nov 1, 2014) from three states: Missouri, Illinois and Colorado. Data were also collected for the same time period of 2013 and 2012. Respiratory specimens from severely ill patients nationwide, who were rhinovirus-positive or enterovirus-positive in hospital testing, were submitted between Aug 1, and Oct 31, 2014, and typed by molecular sequencing. We collected basic clinical and epidemiological characteristics of EV-D68 cases with a standard data collection form submitted with each specimen. We compared patients requiring intensive care with those who did not, and patients requiring ventilator support with those who did not. Mantel-Haenszel χ2 tests were used to test for statistical significance. Findings Regional and hospital-level data from Missouri, Illinois, and Colorado showed increases in respiratory illness between August and September, 2014, compared with in 2013 and 2012. Nationwide, 699 (46%) of 1529 patients tested were confirmed as EV-D68. Among the 614 EV-D68-positive patients admitted to hospital, age ranged from 3 days to 92 years (median 5 years). Common symptoms included dyspnoea (n=513 [84%]), cough (n=500 [81%]), and wheezing (n=427 [70%]); 294 (48%) patients had fever. 338 [59%] of 574 were admitted to intensive care units, and 145 (28%) of 511 received ventilator support; 322 (52%) of 614 had a history of asthma or reactive airway disease; 200 (66%) of 304 patients with a history of asthma or reactive airway disease required intensive care compared with 138 (51%) of 270 with no history of asthma or reactive airway disease (p=0·0004). Similarly, 89 (32%) of 276 patients with a history of asthma or reactive airway disease required ventilator support compared with 56 (24%) of 235 patients with no history of asthma or reactive airway disease (p=0·039). Interpretation In 2014, EV-D68 caused widespread severe respiratory illness across the USA, disproportionately affecting those with asthma. This unexpected event underscores the need for robust surveillance of enterovirus types, enabling improved understanding of virus circulation and disease burden. Funding None. PMID:26482320

A discrete choice experiment to explore patients' willingness to risk disease relapse from treatment withdrawal in psoriatic arthritis.

PubMed

Rothery, Claire; Bojke, Laura; Richardson, Gerry; Bojke, Chris; Moverley, Anna; Coates, Laura; Thorp, Liz; Waxman, Robin; Helliwell, Philip

2016-12-01

The objective of this study is to assess patient preferences for treatment-related benefits and risk of disease relapse in the management of low disease states of psoriatic arthritis (PsA). Focus groups with patients and a literature review were undertaken to determine the characteristics of treatment and symptoms of PsA important to patients. Patient preferences were assessed using a discrete choice experiment which compared hypothetical treatment profiles of the risk and benefits of treatment withdrawal. The risk outcome included increased risk of disease relapse, while benefit outcomes included reduced sickness/nausea from medication and changes in health-related quality of life. Each patient completed 12 choice sets comparing treatment profiles. Preference weights were estimated using a logic regression model, and the maximum acceptable risk in disease relapse for a given improvement in benefit outcomes was elicited. Final sample included 136 patients. Respondents attached the greatest importance to eliminating severe side effects of sickness/nausea and the least importance to a change in risk of relapse. Respondents were willing to accept an increase in the risk of relapse of 32.6 % in order to eliminate the side effects of sickness/nausea. For improvements in health status, the maximum acceptable risk in relapse was comparable to a movement from some to no sickness/nausea. The study suggests that patients in low disease states of PsA are willing to accept greater risks of relapse for improvements in side effects of sickness/nausea and overall health status, with the most important benefit attribute being the elimination of severe sickness or nausea.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

PubMed Central

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

Cost-effectiveness of memantine in moderate and severe Alzheimer's disease in Norway.

PubMed

Rive, B; Aarsland, D; Grishchenko, M; Cochran, J; Lamure, M; Toumi, M

2012-06-01

The cost-effectiveness of memantine for the treatment of moderate and severe Alzheimer's disease has been assessed in several European countries. Objective of the study was to assess it in Norwegian settings. This cost-utility analysis used a Markov modelling approach to simulate the evolution of patients until their need for full-time care (FTC) over a 5-year period. FTC was defined as a patient becoming either dependent or institutionalised. Transition probabilities were estimated using a newly developed predictive equation of time to FTC. Health resource use and utilities were obtained from the Scandinavian Study of Cost and Quality of Life in Alzheimer's Disease study, and mortality was obtained from the Oslo study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine with its alternative in this population, that is no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. The model underwent extensive sensitivity analyses. In Norway, memantine was found to delay the need for FTC by 4.4 weeks compared with standard care and was associated with increased quality-adjusted life years. Memantine was the dominant strategy with cost savings of €3739 (30 041 NOK) per patient. The probability of being the dominant strategy was 98.8%. This result was confirmed across multiple sensitivity analyses. The model suggests that memantine prolongs time to FTC for no additional cost to the healthcare system and society. It can be regarded as a cost-effective choice in the management of moderate and severe Alzheimer's disease. Copyright © 2011 John Wiley & Sons, Ltd.

Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.

PubMed

Philips, Cyriac Abby; Phadke, Nikhil; Ganesan, Karthik; Ranade, Shatakshi; Augustine, Philip

2018-06-21

Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT. Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT. All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes. Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.

Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

PubMed Central

Stone, John H.; Merkel, Peter A.; Spiera, Robert; Seo, Philip; Langford, Carol A.; Hoffman, Gary S.; Kallenberg, Cees G.M.; St. Clair, E. William; Turkiewicz, Anthony; Tchao, Nadia K.; Webber, Lisa; Ding, Linna; Sejismundo, Lourdes P.; Mieras, Kathleen; Weitzenkamp, David; Ikle, David; Seyfert-Margolis, Vicki; Mueller, Mark; Brunetta, Paul; Allen, Nancy B.; Fervenza, Fernando C.; Geetha, Duvuru; Keogh, Karina A.; Kissin, Eugene Y.; Monach, Paul A.; Peikert, Tobias; Stegeman, Coen; Ytterberg, Steven R.; Specks, Ulrich

2011-01-01

BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) PMID:20647199

Disease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology Centre and literature review.

PubMed

Martini, Giorgia; Fadanelli, Gloria; Agazzi, Anna; Vittadello, Fabio; Meneghel, Alessandra; Zulian, Francesco

2018-05-03

Juvenile Localized Scleroderma (JLS) is a rare disorder that may cause severe aesthetic sequelae and functional disability. To date, data on natural history and long-term outcome are discordant and difficult to compare due to the heterogeneity of clinical subtypes, treatments and methods to evaluate activity and outcome in previous studies. A retrospective and cross-sectional study including 133 patients followed between January 1991 and December 2016 was conducted at our Pediatric Rheumatology Centre. Disease course was drawn by retrospective analysis of patients' clinical features, treatment, disease course and outcome at the last evaluation. Disease activity and severity of tissue damage were assessed by using parameters derived from the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) and thermography. Most patients achieved complete remission, as only 12.5%, all with the linear subtype, had still active disease after over 10 years of follow-up. At least one disease relapse occurred in 22.2% of patients and first flare was observed 20 months after first treatment discontinuation. Mild tissue damage was observed in more than half of patients, in 25.4% was moderate and in 23.0% severe; 19.8% presented a functional limitation. The entity of skin and subcutaneous fat loss established at the early stages of the disease as 27.8% of patients with shorter disease duration had severe damage and the rates remained constant in patients with longer follow-up. The delay in start of systemic treatment was associated with longer disease activity and higher relapse rate. Patients with linear scleroderma (LS), pansclerotic morphea (PM) and mixed subtype (MS) presented more severe aesthetic and functional damage but did not differ from other subtypes as for rate of complete remission. JLS in some patients can be a very aggressive disease with persistent activity after >10 years and/or several disease relapses. As tissue damage establishes early in disease course a prompt diagnosis and start of appropriate treatment is crucial to control inflammation, to limit and stabilize damage, before it become irreversible. Clinicians must be aware that children with JLS may present disease reactivation so it is important to closely follow-up patients, particularly in the first 2 years after discontinuation of treatment when disease relapses may occur more frequently. Copyright © 2018 Elsevier B.V. All rights reserved.

Real-world cost-effectiveness of infliximab for moderate-to-severe rheumatoid arthritis in a medium-sized city of China.

PubMed

Li, Jingyang; Wen, Zhenhua; Cai, Anlie; Tian, Feng; Zhang, Liang; Luo, Xiaowen; Deng, Li; He, Jingyun; Yang, Yicheng; Chen, Wendong

2017-05-01

To assess the cost-effectiveness of infliximab-containing therapy (ICT) for moderate-to-severe rheumatoid arthritis (RA) in a medium-sized Chinese city. A Chinese prospective cohort study comparing ICT (25 patients) versus conventional disease-modified antirheumatic drugs (24 patients) for RA was used to assess the cost-effectiveness of ICT. The cohort study observed significantly reduced disease activity score of 28 joints (coefficient -2.718, p < 0.001), improved EQ-5D (coefficient 0.453, p < 0.001) and increased medical costs (coefficient 1.289, p < 0.001) associated with ICT. The incremental cost-effectiveness ratio per gained quality-adjusted life year for ICT versus disease-modified antirheumatic drugs was 1.897-times of the local gross domestic product per capita. Infliximab was a favorable cost-effective alternative option for moderate-to-severe RA in a medium-sized city of China.

Hyaluronic acid concentrations in synovial fluid of dogs with different stages of osteoarthritis.

PubMed

Plickert, H D; Bondzio, A; Einspanier, R; Tichy, A; Brunnberg, L

2013-06-01

To compare hyaluronic acid (HA) concentrations measured in synovial fluid (SF) of joints with different stages of canine secondary osteoarthritis (OA), clinical-orthopedic, radiographic, macroscopic intra-operative and SF findings of 49 joints were assessed. The sum of single findings was correlated to HA concentrations measured by a commercially available ELISA. Joints were categorized into three OA-groups: non-osteoarthritic, mildly osteoarthritic, and severely osteoarthritic. A significant negative correlation was found between severity of OA and HA concentrations (r=-0.696; P<0.001). Median values of HA concentrations decreased with increasing severity of the disease. Statistically significant differences in HA concentrations were observed between the OA-groups (P<0.001). Due to overlapping values between groups, it was concluded that synovial HA concentrations may only indicate a trend of osteoarthritic disease activity, but is not suitable for staging the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ventilation inhomogeneity in obstructive lung diseases measured by electrical impedance tomography: a simulation study.

PubMed

Schullcke, B; Krueger-Ziolek, S; Gong, B; Jörres, R A; Mueller-Lisse, U; Moeller, K

2017-10-10

Electrical impedance tomography (EIT) has mostly been used in the Intensive Care Unit (ICU) to monitor ventilation distribution but is also promising for the diagnosis in spontaneously breathing patients with obstructive lung diseases. Beside tomographic images, several numerical measures have been proposed to quantitatively assess the lung state. In this study two common measures, the 'Global Inhomogeneity Index' and the 'Coefficient of Variation' were compared regarding their capability to reflect the severity of lung obstruction. A three-dimensional simulation model was used to simulate obstructed lungs, whereby images were reconstructed on a two-dimensional domain. Simulations revealed that minor obstructions are not adequately recognized in the reconstructed images and that obstruction above and below the electrode plane may result in misleading values of inhomogeneity measures. EIT measurements on several electrode planes are necessary to apply these measures in patients with obstructive lung diseases in a promising manner.

Relating plaque morphology to respiratory syncytial virus subgroup, viral load, and disease severity in children.

PubMed

Kim, Young-In; Murphy, Ryan; Majumdar, Sirshendu; Harrison, Lisa G; Aitken, Jody; DeVincenzo, John P

2015-10-01

Viral culture plaque morphology in human cell lines are markers for growth capability and cytopathic effect, and have been used to assess viral fitness and select preattenuation candidates for live viral vaccines. We classified respiratory syncytial virus (RSV) plaque morphology and analyzed the relationship between plaque morphology as compared to subgroup, viral load and clinical severity of infection in infants and children. We obtained respiratory secretions from 149 RSV-infected children. Plaque morphology and viral load was assessed within the first culture passage in HEp-2 cells. Viral load was measured by polymerase chain reaction (PCR), as was RSV subgroup. Disease severity was determined by hospitalization, length of stay, intensive care requirement, and respiratory failure. Plaque morphology varied between individual subjects; however, similar results were observed among viruses collected from upper and lower respiratory tracts of the same subject. Significant differences in plaque morphology were observed between RSV subgroups. No correlations were found among plaque morphology and viral load. Plaque morphology did not correlate with disease severity. Plaque morphology measures parameters that are viral-specific and independent of the human host. Morphologies vary between patients and are related to RSV subgroup. In HEp-2 cells, RSV plaque morphology appears unrelated to disease severity in RSV-infected children.

The long-term effectiveness of a lifestyle intervention in severely obese individuals.

PubMed

Unick, Jessica L; Beavers, Daniel; Bond, Dale S; Clark, Jeanne M; Jakicic, John M; Kitabchi, Abbas E; Knowler, William C; Wadden, Thomas A; Wagenknecht, Lynne E; Wing, Rena R

2013-03-01

Severe obesity (body mass index [BMI] ≥40 kg/m(2)) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus, nonsurgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared with overweight (25 ≤BMI <30), class I (30 ≤BMI <35), and class II obese (35 ≤BMI <40) participants. There were 5145 individuals with type 2 diabetes (45-76 years, BMI ≥25 kg/m(2)) randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. Four-year changes in body weight and cardiovascular disease risk factors were assessed. Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education (Ps <.05). At year 4, severely obese lifestyle participants lost 4.9%±8.5%, which was similar to class I (4.8%±7.2%) and class II obese participants (4.4%±7.6%), and significantly greater than overweight participants (3.4%±7.0%; P <.05). Four-year changes in low-density-lipoprotein cholesterol, triglycerides, diastolic blood pressure, HbA(1c), and blood glucose were similar across BMI categories in lifestyle participants; however, the severely obese had less favorable improvements in high-density-lipoprotein cholesterol (3.1±0.4 mg/dL) and systolic blood pressure (-1.4±0.7 mm Hg) compared with the less obese (Ps <.05). Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Severity of mumps disease is related to MMR vaccination status and viral shedding.

PubMed

Gouma, Sigrid; Hahné, Susan J M; Gijselaar, Daphne B; Koopmans, Marion P G; van Binnendijk, Rob S

2016-04-07

During recent years, various mumps outbreaks have occurred among measles, mumps, and rubella (MMR) vaccinated persons in various countries worldwide, including the Netherlands. We studied mumps virus shedding in MMR vaccinated and unvaccinated mumps patients and related these findings to clinical data. In this study, we included 1112 mumps patients of whom diagnostic samples were tested positive in our laboratory between 1 January 2007 and 31 December 2014. We compared mumps virus shedding and severity of disease between patients who had received 2 doses of MMR (n=592) and unvaccinated mumps patients (n=195). Mumps virus shedding in saliva and urine specimens was measured by qPCR. Severity of disease was studied in a subset of patients with clinical data available. Mumps patients who had received 2 MMR doses shed less often mumps virus in their urine than unvaccinated patients. Salivary viral loads were higher at day of onset of disease in twice MMR vaccinated patients with viruria than in twice MMR vaccinated patients without viruria. However, salivary viral loads did not significantly differ between patients who had received 2 MMR doses and unvaccinated patients. Bilateral parotitis and orchitis were less often reported in patients who had received 2 MMR doses than in unvaccinated patients. Furthermore, the prevalence of bilateral parotitis and orchitis was higher among twice MMR vaccinated patients with viruria than among twice MMR vaccinated patients without viruria. MMR vaccination was associated with less severe disease among mumps patients. Systemic spread of virus was associated with more severe disease. The elevated salivary viral loads in patients with systemic mumps disease suggest that these patients pose a higher risk for mumps virus transmission. Our study contributes to the understanding of mumps virus pathogenesis and shows the protective effect of MMR vaccination on severity of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis

PubMed Central

Lessa-Aquino, Carolina; Lindow, Janet C.; Randall, Arlo; Wunder, Elsio; Pablo, Jozelyn; Nakajima, Rie; Jasinskas, Algis; Cruz, Jaqueline S.; Damião, Alcineia O.; Nery, Nívison; Ribeiro, Guilherme S.; Costa, Federico; Hagan, José E.; Reis, Mitermayer Galvão; Ko, Albert I.; Medeiros, Marco Alberto; Felgner, Philip L.

2017-01-01

Background Leptospirosis is an important zoonotic disease worldwide. Humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. Such complications are thought to depend on several factors, including the host immunity. Protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired Leptospira infection. Methods and principal findings Here, we used protein microarray chip to profile the antibody responses of patients with severe and mild leptospirosis against the complete Leptospira interrogans serovar Copenhageni predicted ORFeome. We discovered a limited number of immunodominant antigens, with 36 antigens specific to patients, of which 11 were potential serodiagnostic antigens, identified at acute phase, and 33 were potential subunit vaccine targets, detected after recovery. Moreover, we found distinct antibody profiles in patients with different clinical outcomes: in the severe group, overall IgM responses do not change and IgG responses increase over time, while both IgM and IgG responses remain stable in the mild patient group. Analyses of individual patients’ responses showed that >74% of patients in the severe group had significant IgG increases over time compared to 29% of patients in the mild group. Additionally, 90% of IgM responses did not change over time in the mild group, compared to ~51% in the severe group. Conclusions In the present study, we detected antibody profiles associated with disease severity and speculate that patients with mild disease were protected from severe outcomes due to pre-existing antibodies, while patients with severe leptospirosis demonstrated an antibody profile typical of first exposure. Our findings represent a significant advance in the understanding of the humoral immune response to Leptospira infection, and we have identified new targets for the development of subunit vaccines and diagnostic tests. PMID:28141801

Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies.

PubMed

Maisonneuve, Emeline; Delvin, Edgard; Edgard, Annie; Morin, Lucie; Dubé, Johanne; Boucoiran, Isabelle; Moutquin, Jean-Marie; Fouron, Jean-Claude; Klam, Stephanie; Levy, Emile; Leduc, Line

2015-08-01

Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both fetuses share the same maternal environment. This prospective cohort study involved dichorionic twin pairs, with one co-twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin. Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly. Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxidative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.

Prevalence of anaemia in inflammatory bowel disease in Switzerland: a cross-sectional study in patients from private practices and university hospitals.

PubMed

Voegtlin, Manuela; Vavricka, Stephan R; Schoepfer, Alain M; Straumann, Alex; Voegtlin, Juerg; Rogler, Gerhard; Ballabeni, Pierluigi; Pittet, Valérie; Buser, Andreas; Fried, Michael; Beglinger, Christoph

2010-12-01

Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. 125 patients from RC (66 with Crohn's disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P<0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P=0.032). Supplementation therapy (iron, vitamin B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Reduced retinal nerve fiber layer (RNFL) thickness in ALS patients: a window to disease progression.

PubMed

Rohani, Mohammad; Meysamie, Alipasha; Zamani, Babak; Sowlat, Mohammad Mahdi; Akhoundi, Fahimeh Haji

2018-04-30

To assess RNFL thickness in ALS patients and compare it to healthy controls, and to detect possible correlations between RNFL thickness in ALS patients and disease severity and duration. Study population consisted of ALS patients and age- and sex-matched controls. We used the revised ALS functional rating scale (ALSFRS-R) as a measure of disease severity. RNFL thickness in the four quadrants were measured with a spectral domain OCT (Topcon 3D, 2015). We evaluated 20 ALS patients (40 eyes) and 25 healthy matched controls. Average RNFL thickness in ALS patients was significantly reduced compared to controls (102.57 ± 13.46 compared to 97.11 ± 10.76, p 0.04). There was a significant positive correlation between the functional abilities of the patients based on the ALSFRS-R and average RNFL thickness and also RNFL thickness in most quadrants. A linear regression analysis proved that this correlation was independent of age. In ALS patients, RNFL thickness in the nasal quadrant of the left eyes was significantly reduced compared to the corresponding quadrant in the right eyes even after adjustment for multiplicity (85.80 ± 23.20 compared to 96.80 ± 16.96, p = 0.008). RNFL thickness in ALS patients is reduced compared to healthy controls. OCT probably could serve as a marker of neurodegeneration and progression of the disease in ALS patients. RNFL thickness is different among the right and left eyes of ALS patients pointing to the fact that asymmetric CNS involvement in ALS is not confined to the motor system.

[Clinical importance of semi-quantitative monitoring of lymphomas using the comparative polymerase chain reaction].

PubMed

Slavícková, A; Ivánek, R; Cerný, J; Sálková, J; Trnĕný, M

2002-11-22

PCR techniques detecting interchromosomal translocation and clonal immunoglobulin gene rearrangement (IgH) as disease markers in non-Hodgkin's lymphomas (NHL) has been utilised past ten years. However, qualitative PCR detection of persisted minimal residual disease cannot provide clinically useful prognostic information and presently, quantitative approaches are required to predict patient outcome and assess response to the treatment. In some cases, "end-point" quantifying techniques, such as comparative PCR, are applicable and the relative estimation of differences in target quantity may serve in disease monitoring rather than absolute number of target copies. Our method of comparative PCR employs co-amplification of sequences of interest (clonal CDR3, bcl2/Jh) and the segment of Hras 1 gene(ras) as an internal standard. Serial dilutions of stored diagnostic DNAs from blood and bone marrow are examined in the same PCR and, after gel densitometry, the amount of initial target is assessed by comparing exponential products of co-amplification. The comparative PCR assay was utilized in monitoring of NHL patients cured either with conventional therapy, or with high-dose regimens and transplantation with stem cells, or with chimaeric anti-CD20 monoclonal antibody (Rituximab). Results from 50 monitored intervals obtained during several months up to several years were supplemented with clinical statements retrospectively. Some of patients became PCR-negative, reappearance of PCR-positivity was observed as well. The decrease or increase of disease marker corresponded to clinical observations. Results obtained from bone marrow were in agreement with those obtained from blood. End-point quantifying PCR comparative assay may provide an information on the increased risk of relapse and impact of the therapy. The predictive value of these methods depends on the frequency of sample taking and on the sensitivity of the method, which should be monitored in negative cases.

Health-related quality of life in patients with atopic dermatitis.

PubMed

Maksimović, Nataša; Janković, Slavenka; Marinković, Jelena; Sekulović, Lidija K; Zivković, Zorica; Spirić, Vesna T

2012-01-01

Atopic dermatitis (AD) is a chronic relapsing condition that can have considerable effects on the patients' quality of life (QOL). The aim of this study was to measure the health-related QOL in patients with AD, using generic and specific instruments, to compare the scores obtained by different instruments and to verify the relationship between them. We conducted a cross-sectional study of 132 outpatients with AD. To assess the QOL, Short Form 36 (SF-36), Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) were administered. In order to assess the disease severity of AD, we used the Eczema Area and Severity Index (EASI) and physician assessment of disease severity. Stressful life events during the last 12 months were assessed with Paykel's Interview for Recent Life Events. Patients with AD had inferior social functioning and mental health scores compared with the general population. The correlations between the DLQI and SF-36 were found for the mental components of the QOL. Increasing disease severity was associated with greater impairment in QOL in both, children and adults. Our study found the influence of the stressful life events on the role emotional of AD patients. These results demonstrate that AD influences health-related QOL, especially in children. This study supports the decision to use both generic and skin-specific instruments to assess the impact of AD on QOL. © 2011 Japanese Dermatological Association.

Impact of totally laparoscopic combined management of colorectal cancer with synchronous hepatic metastases on severity of complications: a propensity-score-based analysis.

PubMed

Ratti, Francesca; Catena, Marco; Di Palo, Saverio; Staudacher, Carlo; Aldrighetti, Luca

2016-11-01

Thanks to widespread diffusion of minimally invasive approach in the setting of both colorectal and hepatic surgeries, the interest in combined resections for colorectal cancer and synchronous liver metastases (SCLM) by totally laparoscopic approach (TLA) has increased. Aim of this study was to compare outcome of combined resections for SCLM performed by TLA or by open approach, in a propensity-score-based study. All 25 patients undergoing combined TLA for SCLM at San Raffaele Hospital in Milano were compared in a case-matched analysis with 25 out of 91 patients undergoing totally open approach (TOA group). Groups were matched with 1:2 ratio using propensity scores based on covariates representing disease severity. Main endpoints were postoperative morbidity and long-term outcome. The Modified Accordion Severity Grading System was used to quantify complications. The groups resulted comparable in terms of patients and disease characteristics. The TLA group, as compared to the TOA group, had lower blood loss (350 vs 600 mL), shorter postoperative stay (9 vs 12 days), lower postoperative morbidity index (0.14 vs 0.20) and severity score for complicated patients (0.60 vs 0.85). Colonic anastomosis leakage had the highest fractional complication burden in both groups. In spite of comparable long-term overall survival, the TLA group had better recurrence-free survival. TLA for combined resections is feasible, and its indications can be widened to encompass a larger population of patients, provided its benefits in terms of reduced overall risk and severity of complications, rapid functional recovery and favorable long-term outcomes.

Some consequences of using the Horsfall-Barratt scale for hypothesis testing

USDA-ARS?s Scientific Manuscript database

Comparing treatment effects by hypothesis testing is a common practice in plant pathology. Nearest percent estimates (NPEs) of disease severity were compared to Horsfall-Barratt (H-B) scale data to explore whether there was an effect of assessment method on hypothesis testing. A simulation model ba...

Clinical Severity of Clostridium difficile PCR Ribotype 027: A Case-Case Study

PubMed Central

Morgan, Oliver W.; Rodrigues, Boaventura; Elston, Tony; Verlander, Neville Q.; Brown, Derek F. J.; Brazier, Jonathan; Reacher, Mark

2008-01-01

Background Clostridium difficile is a leading infectious cause of health care associated diarrhoea. Several industrialised countries have reported increased C. difficile infections and outbreaks, which have been attributed to the emergent PCR ribotype 027 strain. Methods and Findings We conducted a case-case study to compare severity of C. difficile disease for patients with 027 versus non-027 ribotypes. We retrospectively collected clinical information about 123/136 patients with C. difficile infections admitted to hospitals in the East of England region in 2006 and from whom stool isolates were cultured and ribotyped as part of an earlier national survey. We defined severe C. difficile disease as having one or more of shock, paralytic ileus, pseudo membranous colitis or toxic megacolon. Patient median age was 83 years old (range 3 to 98, interquartile range 75 to 89), 86% were prescribed antibiotics in the eight weeks before illness onset, 41% had ribotype 027 and 30-day all cause mortality during hospital admission was 21%. Severe disease occurred in 24% (95%CI 13% to 37%) and 17% (95%CI 9% to 27%) of patients with PCR ribotype 027 and non-027 ribotypes respectively. In a multivariable model, ribotype 027 was not associated with severe disease after adjusting for sex, discharge from hospital prior to 60 days of current admission, gastroenteritis on admission, number of initiator antibiotics for C. difficile disease, and hospital where the patient was admitted. Conclusions Our study found no evidence to support previous assertions that ribotype 027 is more virulent than other PCR ribotypes. This finding raises questions about the contribution of this strain to the recent increase in C. difficile disease throughout North America and Europe. PMID:18350149

Clinical severity of Clostridium difficile PCR ribotype 027: a case-case study.

PubMed

Morgan, Oliver W; Rodrigues, Boaventura; Elston, Tony; Verlander, Neville Q; Brown, Derek F J; Brazier, Jonathan; Reacher, Mark

2008-03-19

Clostridium difficile is a leading infectious cause of health care associated diarrhoea. Several industrialised countries have reported increased C. difficile infections and outbreaks, which have been attributed to the emergent PCR ribotype 027 strain. We conducted a case-case study to compare severity of C. difficile disease for patients with 027 versus non-027 ribotypes. We retrospectively collected clinical information about 123/136 patients with C. difficile infections admitted to hospitals in the East of England region in 2006 and from whom stool isolates were cultured and ribotyped as part of an earlier national survey. We defined severe C. difficile disease as having one or more of shock, paralytic ileus, pseudo membranous colitis or toxic megacolon. Patient median age was 83 years old (range 3 to 98, interquartile range 75 to 89), 86% were prescribed antibiotics in the eight weeks before illness onset, 41% had ribotype 027 and 30-day all cause mortality during hospital admission was 21%. Severe disease occurred in 24% (95%CI 13% to 37%) and 17% (95%CI 9% to 27%) of patients with PCR ribotype 027 and non-027 ribotypes respectively. In a multivariable model, ribotype 027 was not associated with severe disease after adjusting for sex, discharge from hospital prior to 60 days of current admission, gastroenteritis on admission, number of initiator antibiotics for C. difficile disease, and hospital where the patient was admitted. Our study found no evidence to support previous assertions that ribotype 027 is more virulent than other PCR ribotypes. This finding raises questions about the contribution of this strain to the recent increase in C. difficile disease throughout North America and Europe.

Clinical efficacy of polyspecific intravenous immunoglobulin therapy in patients with streptococcal toxic shock syndrome: a comparative observational study.

PubMed

Linnér, Anna; Darenberg, Jessica; Sjölin, Jan; Henriques-Normark, Birgitta; Norrby-Teglund, Anna

2014-09-15

Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

PubMed Central

Mac Kenzie, William R.; Heilig, Charles M.; Bozeman, Lorna; Johnson, John L.; Muzanye, Grace; Dunbar, Denise; Jost, Kenneth C.; Diem, Lois; Metchock, Beverly; Eisenach, Kathleen; Dorman, Susan; Goldberg, Stefan

2011-01-01

Background Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. Methods In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. Results African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. Conclusions Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. Trial Registration ClinicalTrials.gov NCT00144417 PMID:21494548

Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease.

PubMed

Stoller, James K; Aboussouan, Loutfi S; Kanner, Richard E; Wilson, Laura A; Diaz, Phil; Wise, Robert

2015-12-01

Alpha-1 antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease, but is underrecognized. Oxygenation and exercise desaturation in individuals with AATD-associated chronic obstructive pulmonary disease has been sparsely studied. The Long-term Oxygen Treatment Trial (LOTT) permits comparing these features of individuals with AATD with alpha-1 antitrypsin-replete (called "usual chronic obstructive pulmonary disease") LOTT participants. Compare demographic, clinical, baseline oxygenation, and exercise desaturation features in participating AATD subjects with those of other LOTT subjects. LOTT is a multicenter randomized controlled trial comparing use of supplemental oxygen versus not in subjects with chronic obstructive pulmonary disease and moderate hypoxemia (resting oxygen saturation as measured by pulse oximetry, 89-93%) or normal oxygen saturation at rest and significant exercise desaturation. Among the 597 LOTT participants with nonmissing alpha-1 antitrypsin levels, 11 (1.8%) had severe AATD and 44 (7.4%) had mild/moderate AATD. Comparison of the 11 severely AAT-deficient individuals with the 542 LOTT participants with usual chronic obstructive pulmonary disease showed that the AATD subjects were younger and despite less smoking, had lower FEV1/FVC (mean post-bronchodilator FEV1/FVC, 0.38 ± 0.06 vs. 0.46 ± 0.13; P = 0.002). Comparison with 27 age-, sex-, and FEV1-matched alpha-1 antitrypsin-normal LOTT participants showed no baseline difference in resting room air pulse oximetry saturation (AATD, 93.6% ± 2.3% vs. 92.7% ± 2.2%; P = 0.64). Exercise-related desaturation was more severe in the individuals with AATD based on desaturation to 88% or less sooner during a 6-minute-walk test, having a higher percentage of desaturation points (e.g., <90%) during exercise, and having a higher distance-saturation product (defined as the distance walked in 6 min multiplied by the nadir saturation achieved during the 6-minute-walk test). These data suggest that individuals with AATD experience more profound desaturation with exercise than age-, sex-, race-, and FEV1-matched control subjects with usual chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00692198).

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

QUALITY OF LIFE IN PATIENTS WITH GRAVES OPHTHALMOPATHY

PubMed Central

Yeatts, R. Patrick

2005-01-01

Purpose To assess the quality of life in patients with Graves ophthalmopathy by means of a prospective questionnaire with validation. Methods A questionnaire containing 105 items was sent to 325 patients seen in our university-based oculoplastic clinic. Two hundred three questionnaires were returned and were suitable for analysis. Fifty-three consecutive patients with Graves disease who presented to the clinic for examination also completed the questionnaire. The questionnaire was validated by administering it to 33 healthy subjects who had no history of Graves disease or thyroid disorder. The results were compared with those of normal subjects and with national norms for visually impaired populations. The relationship of individual questionnaire items to measures of clinical severity was subsequently assessed. Results Patients with Graves ophthalmopathy report greater impairment in both physical (44.4 versus 51.9; P < .001) and mental (43.8 versus 51.8; P < .001) health; poorer self- image (P < .001); and significantly more disturbance in their sleep, social function, and work function (P < .001) than controls. Afflicted patients also experience significantly more diplopia, blurred vision, and dry eye symptoms than controls (P < .001). Individual questionnaire items were found to correlate with clinical disease severity scores and were used to establish a Graves ophthalmopathy quality-of-life questionnaire with disease severity validation. Conclusions Patients with Graves disease are significantly impaired in their social and vocational function because of the ophthalmic manifestations of the disease. A short questionnaire that correlates with clinical measures of disease severity may be a useful measure of quality of life in this disease. PMID:17057811

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

PubMed

Dournon, E; Mayaud, C; Wolff, M; Schlemmer, B; Samuel, D; Sollet, J P; Levasseur-Rajagopalan, P

1990-10-01

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice

PubMed Central

Sumner, Charlotte J.; Wee, Claribel D.; Warsing, Leigh C.; Choe, Dong W.; Ng, Andrew S.; Lutz, Cathleen; Wagner, Kathryn R.

2009-01-01

There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn−/−) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA. PMID:19477958

Usefulness of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

PubMed

Gluhm, Shea; Goldstein, Jody; Brown, Daniel; Van Liew, Charles; Gilbert, Paul E; Corey-Bloom, Jody

2013-10-01

The Montreal Cognitive Assessment (MoCA) is a brief screening instrument for dementia that is sensitive to executive dysfunction. This study examined its usefulness for assessing cognitive performance in mild, moderate, and severe Huntington's disease (HD), compared with the use of the Mini-Mental State Examination (MMSE). We compared MoCA and MMSE total scores and the number of correct answers in 5 cognitive-specific domains in 104 manifest HD patients and 100 matched controls. For the total HD sample, and for the moderate and severe patients, significant differences between both MoCA and MMSE total scores and almost all cognitive-specific domains emerged. Even mild HD subjects showed significant differences with regard to total score and several cognitive domains on both instruments. We conclude that the MoCA, although not necessarily superior to the MMSE, is a useful instrument for assessing cognitive performance over a broad level of functioning in HD. © 2013 Movement Disorder Society.

Psoriasis and polycystic ovary syndrome: a new link in different phenotypes.

PubMed

Moro, Francesca; Tropea, Anna; Scarinci, Elisa; Federico, Alex; De Simone, Clara; Caldarola, Giacomo; Leoncini, Emanuele; Boccia, Stefania; Lanzone, Antonio; Apa, Rosanna

2015-08-01

Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A - patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B - patients with H plus O (without PCO); C - patients with H plus PCO (ovulatory phenotype); D - patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59-13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40-211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01-0.51). The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh

PubMed Central

Andrews, Jason R.; Leung, Daniel T.; Ahmed, Shahnawaz; Malek, Mohammed Abdul; Ahmed, Dilruba; Begum, Yasmin Ara; Qadri, Firdausi; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Nelson, Eric J.

2017-01-01

Background To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings. Methodology/findings We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993–2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41–5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4–12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30–1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens. Conclusions/significance There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset. PMID:28448489

Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh.

PubMed

Andrews, Jason R; Leung, Daniel T; Ahmed, Shahnawaz; Malek, Mohammed Abdul; Ahmed, Dilruba; Begum, Yasmin Ara; Qadri, Firdausi; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Nelson, Eric J

2017-04-01

To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings. We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993-2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41-5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4-12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30-1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens. There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset.

[Description of patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit and identification of severity risk factors].

PubMed

Payet, C; Lutringer-Magnin, D; Cassier, P; Lina, B; Argaud, L; Allaouchiche, B; Vanhems, P

2013-02-01

The authors had for objective to describe patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit (ICU) in a university hospital and to identify risk factors correlated with the severity of the disease. A prospective study was conducted in an university hospital during the A(H1N1)pdm09 influenza pandemic. Severe laboratory confirmed cases (admitted to an ICU) were described and compared with non-severe confirmed cases (not admitted to an ICU). Sixty-nine patients were included; 36 (52%) were 15 to 44 years of age. Sixteen (23%) cases were defined as severe, ten of these (63%) concerned patients 45 to 64 years of age. The independent factors associated with severity were: a history of heart disease, obesity, and tobacco abuse. This work reinforces the need to identify and protect groups at risk of severe outcomes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Prevalence of celiac disease in patients with severe food allergy.

PubMed

Pillon, R; Ziberna, F; Badina, L; Ventura, A; Longo, G; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Patano, G; Not, T; Berti, I

2015-10-01

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

PubMed

De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

2016-08-01

The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

Active Matrixmetalloproteinase-8 and periodontal bacteria - interlink between periodontitis and inflammatory bowel disease?

PubMed

Schmidt, J; Weigert, M; Leuschner, C; Hartmann, H; Raddatz, D; Haak, R; Mausberg, R F; Kottmann, Tanja; Schmalz, G; Ziebolz, D

2018-03-25

The aim of this study was the investigation of concentration and prevalence of selected periodontal pathogenic bacteria and concentration of active matrix-metalloproteinase-8 (aMMP-8) within a group of patients with inflammatory bowel diseases (IBD) and to compare the results with a group of healthy control subjects (HC). 59 IBD patients with Crohn`s disease (CD, n = 30) or ulcerative colitis (UC, n = 29) and 59 HC were included in this cross-sectional study. Based on periodontal probing depth (PPD) and clinical attachment level (CAL), periodontitis was classified into healthy/mild, moderate or severe. aMMP-8 was analyzed from gingival crevicular fluid using enzyme linked immunosorbent assay. Eleven selected periodontal pathogenic bacteria were analyzed in subgingival plaque samples using polymerase chain reaction. IBD patients showed higher CAL (p < 0.01), more severe periodontitis (p = 0.04), gingival bleeding (p < 0.01) and aMMP-8 concentration (p < 0.01) than HC. Only in CD, increasing severity of periodontitis was associated with an increase in aMMP-8 concentration (p = 0.02). The prevalences of Eubacterium nodatum and Eikanella corrodens were significantly lower in IBD compared to HC (p = 0.01). Additionally, the prevalence of Eikanella corrodens was significantly higher in CD compared to UC group (p = 0.04). Further statistically significant differences in selected bacteria between IBD and HC or CD and UC groups could not be found (p > 0.05). The results reveal changes in host immune response of IBD patients in terms of aMMP-8. Only in CD increasing aMMP-8 was associated with severity of periodontal disease. The role of periodontal pathogenic bacteria in the interrelation between IBD and periodontitis remains unclear. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study.

PubMed

Chalasani, Naga; Bonkovsky, Herbert L; Fontana, Robert; Lee, William; Stolz, Andrew; Talwalkar, Jayant; Reddy, K Rajendar; Watkins, Paul B; Navarro, Victor; Barnhart, Huiman; Gu, Jiezhun; Serrano, Jose

2015-06-01

The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency ≤7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Features and Outcomes of 899 Patients with Drug-induced Liver Injury: The DILIN Prospective Study

PubMed Central

Chalasani, N; Bonkovsky, HL; Fontana, R; Lee, W; Stolz, A; Talwalkar, J; Reddy, KR; Watkins, PB; Navarro, V; Barnhart, H; Gu, J; Serrano, J

2015-01-01

Background & Aims The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. Methods In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. Results Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P=.09) and mortality was significantly higher (16% vs 5.2%; P<.001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared to those without liver disease (6.7% vs. 1.5%, p=0.006). Forty-one cases with latency ≤ 7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared to individuals younger than 65 y, individuals 65 y or older (n=149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. Conclusion Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared to patients without. Further studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality. PMID:25754159

Costs and absence of HCV-infected employees by disease stage.

PubMed

Baran, Robert W; Samp, Jennifer C; Walker, David R; Smeeding, James E; Young, Jacob W; Kleinman, Nathan L; Brook, Richard A

2015-01-01

Quantify the costs and absenteeism associated with stages of the Hepatitis C virus (HCV). Retrospective analysis of the HCMS integrated database from multiple geographically diverse, US-based employers with employee information on medical, prescription, and absenteeism claims. Employee data were extracted from July 2001-March 2013. Employees with HCV were identified by ICD-9-CM codes and classified into disease severity cohorts using diagnosis/procedure codes assigning the first date of most severe claim as the index date. Non-HCV employees (controls) were assigned random index dates. Inclusion required 6-month pre-/post-index eligibility. Medical, prescription, and absenteeism cost and time were analyzed using two-part regression (logistic/generalized linear) models, controlling for potentially confounding factors. Costs were inflation adjusted to September 2013. All direct costs comparisons were statistically significant (p ≤ 0.05) with mean medical costs of $1813 [SE = $3] for controls (n = 727,588), $4611 [SE = $211] for non-cirrhotic (n = 1007), $4646 [SE = $721] for compensated cirrhosis (CC, n = 87), $12,384 [SE = $1122] for decompensated cirrhosis (DCC, n = 256), $33,494 [SE = $11,753] for hepatocellular carcinoma (HCC, n = 17) and $97,724 [SE = $32,437] for liver transplant (LT, n = 19) cohorts. Mean short-term disability days/costs were significantly greater for the non-cirrhotic (days = 2.03 [SE = 0.36]; $299 [SE = $53]), DCC (days = 6.20 [SE = 1.36]; $763 [SE = $169]), and LT cohorts (days = 21.98 [SE = 8.21]; $2537 [SE = $972]) compared to controls (days = 1.19 [SE = 0.01]; $155 [SE = $1]). Mean sick leave costs were significantly greater for non-cirrhotic ($373 [SE = $22]) and DCC ($460 [SE = $54]) compared to controls ($327 [SE = $1]). Employees with HCV were shown to have greater direct and indirect costs compared to non-HCV employee controls. Costs progressively increased in the more severe HCV disease categories. Slowing or preventing disease progression may avert the costs of more severe liver disease stages and enable employees with HCV to continue as productive members of the workforce.

The association of periodontal disease with kidney function decline: a longitudinal retrospective analysis of the MrOS dental study.

PubMed

Grubbs, Vanessa; Vittinghoff, Eric; Taylor, George; Kritz-Silverstein, Donna; Powe, Neil; Bibbins-Domingo, Kirsten; Ishani, Areef; Cummings, Steven R

2016-03-01

Identifying modifiable risk factors for chronic kidney disease (CKD) is essential for reducing its burden. Periodontal disease is common, modifiable and has been implicated as a novel potential CKD risk factor, but evidence of its association with kidney function decline over time is limited. In a longitudinal retrospective cohort of 761 elderly men with preserved kidney function [estimated glomerular filtration rate > 60 mL/min/1.73 m(2) using a calibrated creatinine and cystatin C (eGFRcr-cys) equation] at baseline, we performed multivariable Poisson's regression to examine the association of severe periodontal disease with incident CKD, defined as incident eGFRcr-cys <60 mL/min/1.73 m(2) and rapid (>5% annualized) eGFRcr-cys decline. Severe periodontal disease was defined in two ways: (i) ≥5 mm proximal attachment loss in 30% of teeth examined (European Workshop in Periodontology Group C, European Workshop); and (ii) 2+ interproximal sites with attachment loss ≥6 mm and 1+ interproximal sites with probing depth ≥5 mm (Centers for Disease Control/American Academy of Periodontology, CDC/AAP). At baseline, the mean age was 73.4 (SD 4.8) years, the median eGFRcr-cys was 82.4 mL/min/1.73 m(2), and 35.5 and 25.4% of participants had severe periodontal disease by European Workshop and CDC/AAP criteria, respectively. After a mean follow-up of 4.9 years (SD 0.3), 56 (7.4%) participants had incident CKD. Severe periodontal disease was associated with a 2-fold greater rate of incident CKD [incidence rate ratio (IRR) 2.01 (1.21-3.44), P = 0.007] after adjusting for confounders compared with not severe periodontal disease by European Workshop criteria but did not reach statistical significance by CDC/AAP criteria [IRR 1.10 (0.63-1.91), P = 0.9]. Severe periodontal disease may be associated with incident clinically significant kidney function decline among a cohort of elderly men. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Plant Disease Severity Assessment-How Rater Bias, Assessment Method, and Experimental Design Affect Hypothesis Testing and Resource Use Efficiency.

PubMed

Chiang, Kuo-Szu; Bock, Clive H; Lee, I-Hsuan; El Jarroudi, Moussa; Delfosse, Philippe

2016-12-01

The effect of rater bias and assessment method on hypothesis testing was studied for representative experimental designs for plant disease assessment using balanced and unbalanced data sets. Data sets with the same number of replicate estimates for each of two treatments are termed "balanced" and those with unequal numbers of replicate estimates are termed "unbalanced". The three assessment methods considered were nearest percent estimates (NPEs), an amended 10% incremental scale, and the Horsfall-Barratt (H-B) scale. Estimates of severity of Septoria leaf blotch on leaves of winter wheat were used to develop distributions for a simulation model. The experimental designs are presented here in the context of simulation experiments which consider the optimal design for the number of specimens (individual units sampled) and the number of replicate estimates per specimen for a fixed total number of observations (total sample size for the treatments being compared). The criterion used to gauge each method was the power of the hypothesis test. As expected, at a given fixed number of observations, the balanced experimental designs invariably resulted in a higher power compared with the unbalanced designs at different disease severity means, mean differences, and variances. Based on these results, with unbiased estimates using NPE, the recommended number of replicate estimates taken per specimen is 2 (from a sample of specimens of at least 30), because this conserves resources. Furthermore, for biased estimates, an apparent difference in the power of the hypothesis test was observed between assessment methods and between experimental designs. Results indicated that, regardless of experimental design or rater bias, an amended 10% incremental scale has slightly less power compared with NPEs, and that the H-B scale is more likely than the others to cause a type II error. These results suggest that choice of assessment method, optimizing sample number and number of replicate estimates, and using a balanced experimental design are important criteria to consider to maximize the power of hypothesis tests for comparing treatments using disease severity estimates.

Drawings reflect a new dimension of the psychological impact of long-term remission of Cushing's syndrome.

PubMed

Tiemensma, Jitske; Daskalakis, Nikolaos P; van der Veen, Else M; Ramondt, Steven; Richardson, Stephanie K; Broadbent, Elizabeth; Romijn, Johannes A; Pereira, Alberto M; Biermasz, Nienke R; Kaptein, Adrian A

2012-09-01

Drawings can be used to assess perceptions of patients about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions, quality of life (QoL), and clinical disease severity in patients after long-term remission of Cushing's syndrome. We conducted a cross-sectional study including 47 patients with long-term remission of Cushing's syndrome. Patients completed the drawing test, the Illness Perception Questionnaire-Revised, the Short-Form 36, the EuroQoL-5D, and the Cushing QoL. The Cushing's syndrome severity index was scored based on medical records. Characteristics of the drawings were strongly associated with the Cushing's syndrome severity index and severity ratings of health professionals (all P < 0.02). In addition, patients perceived a dramatic change in body size during the active state of the disease compared to the healthy state before disease. Patients reported that their body does not completely return to the original size (i.e. before disease) after treatment. There were no clear associations between characteristics of the drawings and QoL or illness perceptions. This indicates that drawings and QoL or illness perceptions do not share multiple common properties and measure different aspects/dimensions of the disease process. Drawings reflect a new dimension of the psychological impact of long-term remission of Cushing's syndrome because drawings do not share common properties with parameters of QoL or illness perceptions, but do represent the clinical severity of the disease. The assessment of drawings may enable doctors to appreciate the perceptions of patients with long-term remission of Cushing's syndrome and will lead the way in dispelling idiosyncratic beliefs.

Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care

PubMed Central

DE HERT, MARC; CORRELL, CHRISTOPH U.; BOBES, JULIO; CETKOVICH-BAKMAS, MARCELO; COHEN, DAN; ASAI, ITSUO; DETRAUX, JOHAN; GAUTAM, SHIV; MÖLLER, HANS-JURGEN; NDETEI, DAVID M.; NEWCOMER, JOHN W.; UWAKWE, RICHARD; LEUCHT, STEFAN

2011-01-01

The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health outcomes. We searched MEDLINE (1966 – August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depressive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nutritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general population, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the increased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI. PMID:21379357

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia

PubMed Central

Cheng, Po-Jen; Huang, Shang-Yu; Su, Sheng-Yuan; Hsiao, Ching-Hwa; Peng, Hsiu-Huei; Duan, Tao

2016-01-01

Abstract Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia. We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis. There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only. Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients. PMID:26844488

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia.

PubMed

Cheng, Po-Jen; Huang, Shang-Yu; Su, Sheng-Yuan; Hsiao, Ching-Hwa; Peng, Hsiu-Huei; Duan, Tao

2016-02-01

Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients.

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

DOE PAGES

Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

2014-06-10

HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to ε max) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001).more » A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, ε max, was significantly (p≤0.032) associated with increasing severity of liver disease (ε max[s.e.]=0.86[0.05], ε max=0.69[0.06] and ε max=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log 10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

[Objective assessment of the functional impact of dry eye severity on the quality of vision by double-pass aberrometry].

PubMed

Habay, T; Majzoub, S; Perrault, O; Rousseau, C; Pisella, P J

2014-03-01

To assess the functional impact of the severity of dry eye on the quality of vision by measuring an Objective Scatter Index (OSI) using double pass aberrometry. Twenty-eight patients (56 eyes) with dry eye syndromes of varying severity participated in this study. A double-pass aberrometer was used to measure the dynamic changes in the OSI for 20 seconds. The mean and standard deviations of the OSI and the number of blinks occurring during the examination were compared as a function of the clinical severity of dry eye disease. The mean OSI increased with the severity of dry eye syndrome with a significant difference for stages 3 (P<0.01) and 4 (P<0.001) compared to stages 1 and 2, without a significant difference based on age (P>0.8) or visual acuity (P>0.2). Standard deviation of the OSI also increased with the severity of dry eye disease, with a significant difference for stages 3 (P<0.01) and 4 (P<0.0001) compared to stages 1 and 2, with no significant increase in the number of blinks (P>0.2). The values of the OSI standard deviation represented the dynamic nature of aberrometric changes related to the instability of the tear film. Quality of vision of patients deteriorated in relation to the severity of their dry eye. The analysis of OSI standard deviation appears to be an objective way to assess the intensity of subjective visual disturbances reported by patients with dry eye syndrome. It also provides a new tool to assess the severity of damage to the ocular surface. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Mortality causes and outcomes in Indigenous populations of Canada, the United States, and Australia with rheumatic disease: A systematic review.

PubMed

Hurd, Kelle; Barnabe, Cheryl

2018-02-01

Indigenous populations of Canada, America, Australia, and New Zealand have increased rates and severity of rheumatic disease. Our objective was to summarize mortality outcomes and explore disease and social factors related to mortality. A systematic search was performed in medical (Medline, EMBASE, and CINAHL), Indigenous and conference abstract databases (to June 2015) combining search terms for Indigenous populations and rheumatic diseases. Studies were included if they reported measures of mortality (crude frequency, mortality rate, survival, and potential years of life lost (PYLL)) in Indigenous populations from the four countries. Of 5269 titles and abstracts identified, 504 underwent full-text review and 12 were included. No studies from New Zealand were found. In five Canadian studies of systemic lupus erythematosus (SLE) patients, First Nations ethnicity was associated with lower survival after adjusting for disease and social factors, and an increased frequency of death from lupus and its complications compared to Caucasians was found. All-cause mortality was higher in Native Americans (n = 2 studies) relative to Whites with SLE after adjusting for disease and social factors, but not in those with lupus nephritis alone. Australian Aborigines with SLE frequently developed infection and lupus complications leading to death (n = 3 studies). Mortality rates were increased in Pima Indians in the United States with rheumatoid arthritis (RA) compared to those without RA. One study in Native Americans with scleroderma found nearly all deaths were related to progressive disease. Canadian and American Indigenous populations with SLE have increased mortality rates compared to Caucasian populations. Mortality in Canadian and Australian Indigenous populations with SLE, and in Native American populations with RA and scleroderma, is frequently attributed to disease progression or complications. The proportional attribution of rheumatic disease severity and social factors to mortality and complications leading to death between Indigenous and non-Indigenous populations has not been fully evaluated. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency.

PubMed

Parr, David G; Guest, Peter G; Reynolds, John H; Dowson, Lee J; Stockley, Robert A

2007-12-15

alpha(1)-Antitrypsin (AAT) deficiency is associated with increased risk of chronic obstructive pulmonary disease (COPD), in particular emphysema, but airway disease is less well described. To assess the prevalence of airways disease in subjects with AAT deficiency and to identify the relationship between radiological airway abnormalities and clinical phenotype. We characterized the computed tomographic phenotype of 74 subjects (PiZ), using visual scoring of airway disease and densitometric assessment of emphysema. Computed tomographic measurements were related to physiology, health status (St. George's Respiratory Questionnaire), and emphysema severity, and the relative impact of airway disease and emphysema severity on health status and airflow obstruction was compared by stepwise regression. Bronchiectatic changes were seen in 70 subjects, and a subgroup with a bronchiectasis-predominant phenotype was identified. Clinically significant bronchiectasis (radiologic bronchiectasis in 4 or more bronchopulmonary segments together with symptoms of regular sputum production) occurred in 20 subjects (27%). AAT-deficient index cases had higher airway disease scores (P < 0.05), more severe emphysema (P < 0.001), and greater impairment of physiology (P < 0.001) and health status (P < 0.05) than nonindex cases. Airway disease scores correlated with health status, and bronchial wall thickening correlated with FEV(1). Regression analysis indicated that emphysema severity had the strongest associations for health status (r = 0.505, P < 0.001) and FEV(1) (r = 0.699, P < 0.001), but the addition of airway disease score improved the regression models (r = 0.596, P = 0.002 and r = 0.783, P < 0.001, respectively). Emphysema is the predominant component of COPD in AAT deficiency, but the prevalence and impact of airway disease are greater than currently recognized. Consequently, future therapeutic strategies in AAT deficiency should also target this component of COPD.

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

PubMed

Rostami-Nejad, Mohammad; Hejazi, Seyed Hossein; Peña, Amado Salvador; Asadzadeh-Aghdaei, Hamid; Rostami, Kamran; Volta, Umberto; Zali, Mohammad Reza

2018-05-18

It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection. In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification. High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities. CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.

Severity of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD): Proposal for a New Classification.

PubMed

Coton, Sonia; Vollmer, William M; Bateman, Eric; Marks, Guy B; Tan, Wan; Mejza, Filip; Juvekar, Sanjay; Janson, Christer; Mortimer, Kevin; P A, Mahesh; Buist, A Sonia; Burney, Peter G J

2017-10-01

Current classifications of Chronic Obstructive Pulmonary Disease (COPD) severity are complex and do not grade levels of obstruction. Obstruction is a simpler construct and independent of ethnicity. We constructed an index of obstruction severity based on the FEV 1 /FVC ratio, with cut-points dividing the Burden of Obstructive Lung Disease (BOLD) study population into four similarly sized strata to those created by the GOLD criteria that uses FEV 1 . We measured the agreement between classifications and the validity of the FEV 1 -based classification in identifying the level of obstruction as defined by the new groupings. We compared the strengths of association of each classification with quality of life (QoL), MRC dyspnoea score and the self-reported exacerbation rate. Agreement between classifications was only fair. FEV 1 -based criteria for moderate COPD identified only 79% of those with moderate obstruction and misclassified half of the participants with mild obstruction as having more severe COPD. Both scales were equally strongly associated with QoL, exertional dyspnoea and respiratory exacerbations. Severity assessed using the FEV 1 /FVC ratio is only in moderate agreement with the severity assessed using FEV 1 but is equally strongly associated with other outcomes. Severity assessed using the FEV 1 /FVC ratio is likely to be independent of ethnicity.

Severe Graves' ophthalmopathy may be a risk factor for the development of postthyroidectomy hypocalcaemia.

PubMed

Hassan, I; Danila, R; Maurer, E; Osei-Agymang, T; Zielke, A

2008-11-01

The aim of this study was to compare the rate of hypocalcaemia after thyroid resection in patients with versus patients without Graves' Ophthalmopathy (GO). 153 patients following thyroid surgery for Grave's disease were studied. Patients were divided into three groups according to the severity of GO at the time of surgery using the NOSPECS classification. Subgroup I comprised of 70 patients without GO, subgroup II comprised of 63 patients with moderate GO and 20 patients with severe GO were assigned to Subgroup III. Association between severe ophthalmopathy and postoperative hypocalcaemia after thyroidectomy was investigated. 12/70 patients complained transient and 3/70 permanent hypocalcemia within subgroup I. 14/63 patients developed transient and 4/63 patients permanent hypocalcaemia within subgroup II. There were 7/20 patients with transient and 5/20 cases with permanent hypocalcaemia in the patient group with severe GO (subgroup III). The incidence of permanent postthyroidectomy hypocalcaemia was significantly higher in the subgroup III with severe GO when compared to the subgroup I without GO (p=0.004). Although postthyroidectomy hypocalcemia seems to be a multifactorial phenomenon, this study implicates unknown role of severe GO at time of surgery in the development of hypocalcaemia after thyroid surgery for Graves' disease. Therefore, patients with GO should be considered for surgery at high volume centres specialised in thyroid and parathyroid surgery.

A population-based study of severity in patients with acute on chronic pancreatitis.

PubMed

Akshintala, Venkata S; Hutfless, Susan M; Yadav, Dhiraj; Khashab, Mouen A; Lennon, Anne Marie; Makary, Martin A; Hirose, Kenzo; Andersen, Dana K; Kalloo, Anthony N; Singh, Vikesh K

2013-11-01

The objectives of this study were to evaluate the severity of patients with acute pancreatitis (AP) on chronic pancreatitis (CP) and compare this to patients with AP without CP. The Maryland Health Services database was queried for all adult inpatient discharges with a primary diagnosis of AP from 1994 to 2010. Acute pancreatitis on CP and AP without CP were defined by the presence of the associated diagnosis code for CP. Severity was defined as organ failure, intensive care unit stay, or mortality. Acute pancreatitis on CP accounted for 13.7% of all AP discharges (9747/70,944). The proportion of AP-on-CP discharges doubled during the study period (8.8% to 17.6%; P < 0.0001). When compared with patients with AP without CP, AP-on-CP patients were younger, were more likely to be male and black, had higher rates of alcohol and drug abuse, and had less severe disease with lower rates of mortality, organ failure, need for mechanical ventilation, and intensive care unit stay. Among AP-on-CP patients, significant predictors of severity included advanced age, weight loss, and 2 or more comorbidities. Patients with AP on CP have less severe disease than do those with AP without CP. Weight loss, advanced age, and comorbidity increase the risk of severity in patients with AP on CP.

Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life.

PubMed

Pace, F; Molteni, P; Bollani, S; Sarzi-Puttini, P; Stockbrügger, R; Bianchi Porro, G; Drossman, D A

2003-10-01

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are intestinal diseases perceived differently by patients and doctors: the former is considered essentially as an 'organic' disease (i.e. an illness in which the role of stress or psychological factors is at best secondary to the disease itself), whereas the latter is acknowledged as a 'functional' disorder (i.e. illness thought to be more in the 'mind' than in the body of the patient). Accordingly, the respective impact of the two diseases on patients' health-related quality of life (HRQOL) is perceived to be very different. We aimed to compare the relative impact of the disease on HRQOL, psychological profile and perceived burden of stressful life events in two groups of outpatients suffering from IBS and IBD and attending our outpatient department at an Italian university hospital. Eighty patients with IBD (26 with ulcerative colitis and 54 with Crohn disease) and 85 controls with IBS formed the patient samples of the study. Three questionnaires were given to the patients while they were attending the outpatient department because of their previously diagnosed disease, namely the SF-36 (a generic well-validated tool for measuring HRQOL), the SCL-90 (for assessing the psychological profile of patients), and the Holmes & Rahe schedule (for the assessment of stressful life experiences). The results were then compared by means of analysis of variance (ANOVA) and Bonferroni-adjusted t test, when appropriate. HRQOL appeared to be similarly reduced in both disease groups (SF-36 overall mean value: 58.2 +/- 16.1 in IBS patients versus 56.4 +/- 22.3 in IBD patients: P > 0.05) in comparison with normative Italian data. Furthermore, the overall severity of psychological symptoms was not statistically different between patients suffering from IBD versus IBS, as shown by SCL-90 mean scores of 0.89 + 0.45 versus 0.83 +/- 0.48, respectively (P > 0.05). On the contrary, the severity of recent stressful life experiences was perceived to be higher by IBS than by IBD patients (mean SRE score: 110.8 = 110.2 versus 61.6 +/- 78.8; P < 0.05). Our study supports the notion that, at least in referral centres, patients with IBS show health-related quality of life, psychological distress and recent occurrence of stressful life events of severity at least comparable with age-matched IBD patients.

Comparing mortality between coronary artery bypass grafting and percutaneous coronary intervention with drug-eluting stents in elderly with diabetes and multivessel coronary disease.

PubMed

Naito, Ryo; Miyauchi, Katsumi; Konishi, Hirokazu; Tsuboi, Shuta; Ogita, Manabu; Dohi, Tomotaka; Kajimoto, Kan; Kasai, Takatoshi; Tamura, Hiroshi; Okazaki, Shinya; Isoda, Kikuo; Yamamoto, Taira; Amano, Atsushi; Daida, Hiroyuki

2016-09-01

Coronary artery disease is a critical issue that requires physicians to consider appropriate treatment strategies, especially for elderly people who tend to have several comorbidities, including diabetes mellitus (DM) and multivessel disease (MVD). Several studies have been conducted comparing clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in patients with DM and MVD. However, elderly people were excluded in those clinical studies. Therefore, there are no comparisons of clinical outcomes between CABG and PCI in elderly patients with DM and MVD. We compared all-cause mortality between PCI with drug-eluting stents (DES) and CABG in elderly patients with DM and MVD. A total of 483 (PCI; n = 256, CABG; n = 227) patients were analyzed. The median follow-up period was 1356 days (interquartile range of 810-1884). The all-cause mortality rate was not significantly different between CABG and PCI with DES groups. The CABG group had more patients with complex coronary lesions such as three-vessel disease or a left main trunk lesion. Older age, hemodialysis, and reduced LVEF were associated with increased long-term all-cause mortality in a multivariable Cox regression analysis. The rate of all-cause mortality was not significantly different between the PCI and CABG groups in elderly patients with DM and MVD in a single-center study.

Effects of Levodopa on Postural Strategies in Parkinson’s disease

PubMed Central

Mancini, Martina; Rocchi, Laura; Horak, Fay

2017-01-01

Altered postural control and balance are major disabling issues of Parkinson’s disease (PD). Static and dynamic posturography have provided insight into PD’s postural deficits; however, little is known about impairments in postural coordination. We hypothesized that subjects with PD would show more ankle strategy during quiet stance than healthy control subjects, who would include some hip strategy, and this stiffer postural strategy would increase with disease progression. We quantified postural strategy and sway dispersion with inertial sensors (one placed on the shank and one on the posterior trunk at L5 level) while subjects were standing still with their eyes open. A total of 70 subjects with PD, including a mild group (H&Y≤2, N=33) and a more severe group (H&Y≥3, N=37), were assessed while OFF and while ON levodopa medication. We also included a healthy control group (N=21). Results showed an overall preference of ankle strategy in all groups while maintaining balance. Postural strategy was significantly lower ON compared to OFF medication (indicating more hip strategy), but no effect of disease stage was found. Instead, sway dispersion was significantly larger in ON compared to OFF medication, and significantly larger in the more severe PD group compared to the mild. In addition, increased hip strategy during stance was associated with poorer self-perception of balance. PMID:27131172

Effects of Levodopa on Postural Strategies in Parkinson's disease.

PubMed

Baston, Chiara; Mancini, Martina; Rocchi, Laura; Horak, Fay

2016-05-01

Altered postural control and balance are major disabling issues of Parkinson's disease (PD). Static and dynamic posturography have provided insight into PD's postural deficits; however, little is known about impairments in postural coordination. We hypothesized that subjects with PD would show more ankle strategy during quiet stance than healthy control subjects, who would include some hip strategy, and this stiffer postural strategy would increase with disease progression. We quantified postural strategy and sway dispersion with inertial sensors (one placed on the shank and one on the posterior trunk at L5 level) while subjects were standing still with their eyes open. A total of 70 subjects with PD, including a mild group (H&Y≤2, N=33) and a more severe group (H&Y≥3, N=37), were assessed while OFF and while ON levodopa medication. We also included a healthy control group (N=21). Results showed an overall preference of ankle strategy in all groups while maintaining balance. Postural strategy was significantly lower ON compared to OFF medication (indicating more hip strategy), but no effect of disease stage was found. Instead, sway dispersion was significantly larger in ON compared to OFF medication, and significantly larger in the more severe PD group compared to the mild. In addition, increased hip strategy during stance was associated with poorer self-perception of balance. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative evaluation of serum C-reactive protein levels in chronic and aggressive periodontitis patients and association with periodontal disease severity

PubMed Central

Goyal, Lata; Bey, Afshan; Gupta, N. D.; Sharma, Vivek Kumar

2014-01-01

Objective: C-reactive protein (CRP) is an acute-phase reactant and has been proved to be a significant predictor of future cardiovascular events. Recent studies have demonstrated a correlation between periodontitis and elevated CRP levels. However, most of the studies have focused on chronic periodontitis and very few studies are done in patients with aggressive periodontitis. The aim of this study was to determine and compare the relative levels of serum CRP in aggressive and chronic periodontitis patients. Materials and Methods: A total of 75 systemically healthy subjects were divided into three groups: Group I, nonperiodontitis subjects; group II, chronic generalized periodontitis patients and group III, generalized aggressive periodontitis patients. All participants were subjected to quantitative CRP analysis using enzyme-linked immunosorbent assay. Results: Mean CRP levels were significantly greater in both group II and III as compared to group I and group III having greater level than group II. Furthermore, CRP levels positively correlated with the amount of periodontal destruction as measured by probing depth and clinical attachment loss. Conclusion: The present study indicates a positive correlation between CRP and periodontal disease severity with particular concern in younger individuals that could be a possible underlying pathway in the association between periodontal disease and the observed higher risk for cardiovascular disease in periodontitis patients. PMID:25395764

Anxiety and depression in adult outpatients with bronchiectasis: Associations with disease severity and health-related quality of life.

PubMed

Gao, Yong-Hua; Guan, Wei-Jie; Zhu, Ya-Nan; Chen, Rong-Chang; Zhang, Guo-Jun

2018-04-01

Anxiety and depression might frequently affect bronchiectasis patients, but data in Chinese patients, including their association with disease severity assessed with Bronchiectasis Severity Index (BSI) and FACED score, are limited. To investigate the rate, risk factors, association with disease severity and impact of anxiety and depression on health-related quality of life (HRQoL) in adult outpatients with steady-state bronchiectasis. This cross-sectional study included 163 outpatients (102 females; mean age, 45.8 years) and 80 healthy subjects (47 females; mean age, 47.1 years). Demographic, clinical indices, radiology, spirometry, aetiology, sputum bacteriology, Hospital Anxiety and Depression Scales (HADS), Pittsburgh Sleep Quality Index (PSQI) and St. George's Respiratory Questionnaire (SGRQ) were assessed. Patients with steady-state bronchiectasis had a higher rate of depression (HADS-depression >7) (30.1% vs 10.0%, P = .001) and anxiety (HADS-anxiety >7; 39.9% vs 6.3%, P < .001) compared with healthy subjects. Notably, no significant differences in the rate of anxiety and depression were found across different disease severity, assessed with BSI and FACED score (all P > .05). In multivariate model, factors associated with anxiety included younger age (OR = 1.05), education below college graduate (OR = 4.55) and sleep disturbance (PSQI ≥ 6; OR = 2.95); whereas sleep disturbance was the sole factor associated with depression (OR = 5.98). Patients with either depression or anxiety had more markedly impaired HRQoL affecting most domains than those without. Anxiety and depression are common in bronchiectasis and can negatively affect HRQoL, but not related to disease severity. Prompt assessment and treatment of these mental disorders, regardless of bronchiectasis severity, are advocated and might improve HRQoL. © 2017 John Wiley & Sons Ltd.

Multicenter, randomized, double-blind study comparing 20 and 40 mg of pantoprazole for symptom relief in adolescents (12 to 16 years of age) with gastroesophageal reflux disease (GERD)

USDA-ARS?s Scientific Manuscript database

An age-appropriate questionnaire (GASP-Q) was used to assess the frequency and severity of the gastroesophageal reflux disease (GERD) symptoms: abdominal/belly pain, chest pain/heartburn, pain after eating, nausea, burping/belching, vomiting/regurgitation, choking when eating, and difficulty swallow...

Perceptual Measures of Speech from Individuals with Parkinson's Disease and Multiple Sclerosis: Intelligibility and beyond

ERIC Educational Resources Information Center

Sussman, Joan E.; Tjaden, Kris

2012-01-01

Purpose: The primary purpose of this study was to compare percent correct word and sentence intelligibility scores for individuals with multiple sclerosis (MS) and Parkinson's disease (PD) with scaled estimates of speech severity obtained for a reading passage. Method: Speech samples for 78 talkers were judged, including 30 speakers with MS, 16…

First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

PubMed Central

Ng, Jowin Kai Wei; Zhang, Summer Lixin; Tan, Hwee Cheng; Yan, Benedict; Maria Martinez Gomez, Julia; Tan, Wei Yu; Lam, Jian Hang; Tan, Grace Kai Xin; Ooi, Eng Eong; Alonso, Sylvie

2014-01-01

Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations. Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved. PMID:24699622

Sleep-wake differences in scaling behavior of the human heartbeat: analysis of terrestrial and long-term space flight data

NASA Technical Reports Server (NTRS)

Bunde, A.; Amaral, L. A.; Havlin, S.; Fritsch-Yelle, J.; Baevsky, R. M.; Stanley, H. E.; Goldberger, A. L.

1999-01-01

We compare scaling properties of the cardiac dynamics during sleep and wake periods for healthy individuals, cosmonauts during orbital flight, and subjects with severe heart disease. For all three groups, we find a greater degree of anticorrelation in the heartbeat fluctuations during sleep compared to wake periods. The sleep-wake difference in the scaling exponents for the three groups is comparable to the difference between healthy and diseased individuals. The observed scaling differences are not accounted for simply by different levels of activity, but appear related to intrinsic changes in the neuroautonomic control of the heartbeat.

Mean platelet volume is associated with disease severity in patients with obstructive sleep apnea syndrome

PubMed Central

Akyol, Selahattin; Çörtük, Mustafa; Baykan, Ahmet Oytun; Kiraz, Kemal; Börekçi, Abdurrezzak; Şeker, Taner; Gür, Mustafa; Çayli, Murat

2015-01-01

OBJECTIVE: Obstructive sleep apnea syndrome is associated with cardiovascular diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor of cardiovascular thromboembolic events. The aim of the present study is to investigate the association between the MPV and disease severity in patients with obstructive sleep apnea syndrome. METHODS: We prospectively included 194 obstructive sleep apnea syndrome patients without cardiovascular disease (mean age 56.5±12.5 years) who were undergoing sleep tests. An overnight full laboratory polisomnography examination was conducted on each patient. The patients were divided into 3 groups according to the apnea-hypopnea index (AHI): (1) AHIlow group: 5≤AHI<15, (2) AHImid group: 1530. RESULTS: The highest MPV values were found in the AHIhigh group compared with other groups (p<0.05 for all). Multiple linear regression analysis indicated that the MPV was associated with the AHI (β=0.500, p<0.001) and the high sensitivity C-reactive protein (hs-CRP) level (β=0.194, p=0.010). CONCLUSION: The MPV is independently associated with both disease severity and inflammation in patients with obstructive sleep apnea syndrome. PMID:26222817

Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease.

PubMed

Douglas, Madeline G; Kocher, Jacob F; Scobey, Trevor; Baric, Ralph S; Cockrell, Adam S

2018-04-01

We recently established a mouse model (288-330 +/+ ) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10 6 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10 3 and 10 5 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10-1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics and severity of preeclampsia in young and elderly gravidas with hypertensive disease.

PubMed

Rymer-Haskel, Noa; Schushan-Eisen, Irit; Hass, Yigal; Rahav, Roni; Maayan-Metzger, Ayala; Hendler, Israel

2018-06-01

Advanced maternal age (AMA) is associated with increased risk for preeclampsia, however, a paucity of data exists regarding the characteristics of the disease in this age group. Our aim was to compare the characteristics and severity of preeclampsia in older and younger gravidas. A retrospective, small case control study of women diagnosed with preeclampsia in a single tertiary care center. Nulliparous women ≥40 years old with singleton pregnancies ≥ 24 0/7 weeks' gestation were matched (1:2 ratio) with young (20-34 years old) nulliparous women. The rate of severe preeclampsia (60.9 vs 69.6% respectively), HELLP, eclampsia or the need for magnesium treatment did not differ between the groups. However, the AMA group had an increased rate of postpartum presentation or exacerbation of preeclampsia compared to the control group (50.0 vs. 28.3% respectively, p = 0.01). In the AMA group, 93.5% of births were by cesarean section (CS) compared to 52.2% in the control group (p < 0.0001). There was no difference in birthweight, rate of small for gestational age or composite neonatal morbidity between the groups. Preeclampsia at an advanced maternal age carries a similar rate of severe preeclampsia and complications as in young women. However, women over 40 years old have an increased risk for presentation or exacerbation of preeclampsia in the postpartum period and an increased rate of CS compared to younger gravidas. Copyright © 2018 Elsevier B.V. All rights reserved.

Danger ahead: the burden of diseases, injuries, and risk factors in the Eastern Mediterranean Region, 1990-2015.

PubMed

2018-05-01

The Eastern Mediterranean Region faces several health challenges at a difficult time with wars, unrest, and economic change. We used the Global Burden of Disease 2015 study to present the burden of diseases, injuries, and risk factors in the Eastern Mediterranean Region from 1990 to 2015. Ischemic heart disease was the leading cause of death in the region in 2015, followed by cerebrovascular disease. Changes in total deaths ranged from a reduction of 25% for diarrheal diseases to an increase of about 42% for diabetes and tracheal, bronchus, and lung cancer. Collective violence and legal intervention increased by 850% during the time period. Diet was the leading risk factor for disability-adjusted life years (DALYs) for men compared to maternal malnutrition for females. Childhood undernutrition was the leading risk factor for DALYs in 1990 and 2005, but the second in 2015 after high blood pressure. Our study shows that the region is facing several health challenges and calls for global efforts to stabilise the region and to address the current and future burden of disease.

Inflammatory Bowel Disease and the Risk of Autoimmune Diseases.

PubMed

Wilson, J Claire; Furlano, Raoul I; Jick, Susan S; Meier, Christoph R

2016-02-01

An increased risk of autoimmune disease has been reported in patients with inflammatory bowel disease [IBD]. Using data from the Clinical Practice Research Datalink [CPRD], this study set out to further examine this relationship. Patients with a first-time IBD diagnosis were randomly matched to an equal-sized IBD-free comparison group. Incidence rates for new-onset autoimmune diseases were estimated. A nested case-control analysis comprising IBD patients was conducted, using conditional logistic regression to assess whether IBD severity, duration, or treatment influences the risk of developing autoimmune diseases. During follow-up, 1069 IBD and 585 IBD-free patients developed an incident autoimmune disease. An increased incidence of autoimmune disease was observed in IBD patients (incidence rate [IR] 9.65, 95% confidence interval [CI] 9.09-10.24) compared with the non-IBD comparison group [IR 5.22, 95% CI 4.82-5.66]. In IBD patients, increased disease severity was associated with an increased risk of autoimmune disease development (odds ratio [OR] 1.62, 95% CI 1.28-2.05). Current antibiotic use was also associated with an increased risk [adjusted OR 1.72, 95% CI 1.07-2.78]. A reduced risk of incident autoimmune diseases was observed for current long-term users of aminosalicylates [adjusted OR 0.72, 95% CI 0.57-0.91]. Individuals with IBD had an increased risk of developing an autoimmune disease. Increased disease severity and current antibiotic use were associated with an increased relative risk of developing additional autoimmune diseases in IBD patients. Long-term current aminosalicylate use was associated with a reduced risk. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Microbiota and Metatranscriptome Changes Accompanying the Onset of Gingivitis

PubMed Central

2018-01-01

ABSTRACT Over half of adults experience gingivitis, a mild yet treatable form of periodontal disease caused by the overgrowth of oral microbes. Left untreated, gingivitis can progress to a more severe and irreversible disease, most commonly chronic periodontitis. While periodontal diseases are associated with a shift in the oral microbiota composition, it remains unclear how this shift impacts microbiota function early in disease progression. Here, we analyzed the transition from health to gingivitis through both 16S v4-v5 rRNA amplicon and metatranscriptome sequencing of subgingival plaque samples from individuals undergoing an experimental gingivitis treatment. Beta-diversity analysis of 16S rRNA reveals that samples cluster based on disease severity and patient but not by oral hygiene status. Significant shifts in the abundance of several genera occurred during disease transition, suggesting a dysbiosis due to development of gingivitis. Comparing taxonomic abundance with transcriptomic activity revealed concordance of bacterial diversity composition between the two quantification assays in samples originating from both healthy and diseased teeth. Metatranscriptome sequencing analysis indicates that during the early stages of transition to gingivitis, a number of virulence-related transcripts were significantly differentially expressed in individual and across pooled patient samples. Upregulated genes include those involved in proteolytic and nucleolytic processes, while expression levels of those involved in surface structure assembly and other general virulence functions leading to colonization or adaptation within the host are more dynamic. These findings help characterize the transition from health to periodontal disease and identify genes associated with early disease. PMID:29666288

Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease.

PubMed

Yamashita, Koji; Hiwatashi, Akio; Togao, Osamu; Kikuchi, Kazufumi; Yamaguchi, Hiroo; Suzuki, Yuriko; Kamei, Ryotaro; Yamasaki, Ryo; Kira, Jun-Ichi; Honda, Hiroshi

2017-06-01

To evaluate cerebral blood flow (CBF) laterality derived from arterial spin labeling (ASL) in early-stage Parkinson's disease (PD) patients compared with those with advanced stages. Thirty-eight patients with PD (21 patients in early stages, 17 patients in advanced stages) were retrospectively studied. The CBF maps derived from 3T ASL data were co-registered to the corresponding 3DT1WI using SPM 12 software. Caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were manually traced on the representative axial slices of 3DT1WI. CBF of the CN, PT, GP, and TH was measured using corresponding pixels on the co-registered CBF maps. A laterality index (LI) was calculated as the ratio of the contralateral CBF to primary affected side CBF. Each LI was compared between early and advanced stages of PD using the Mann-Whitney U-test. The LIs were also compared between each stage of PD. In the CN, the LIs were significantly higher in early stages (mean LI ± SD, 95% confidence interval = 1.06 ± 0.14, 1.00-1.13) than in advanced stages (0.94 ± 0.14, 0.87-1.01; P < 0.05). We also observed a tendency toward decreased LIs with disease severity (1.10 ± 0.14, 0.99-1.21 for Hoehn and Yahr stage I; 1.04 ± 0.14, 0.92-1.12 for stage II; 0.96 ± 0.11, 0.89-1.10 for stage III; 0.93 ± 0.17, 0.81-1.05 for stage IV). The evaluation of CBF laterality pattern in the CN using ASL may be useful for assessing the disease severity of PD patients. 3 J. MAGN. RESON. IMAGING 2017;45:1821-1826. © 2016 International Society for Magnetic Resonance in Medicine.

Biomechanical deviations during level walking associated with knee osteoarthritis: a systematic review and meta-analysis.

PubMed

Mills, Kathryn; Hunt, Michael A; Ferber, Reed

2013-10-01

To identify which gait deviations are consistently associated with knee osteoarthritis (KOA) and how these are influenced by disease severity, the involved compartment, and sex. Five electronic databases and reference lists of publications were searched. Cross-sectional, observational studies comparing temporospatial variables, joint kinematics, and joint moments between individuals with KOA and healthy controls or between KOA subgroups were considered for review. Only publications scoring ≥50% on a modified methodology quality index were included. Because of the number of gait deviations examined, only biomechanical variables reported by ≥4 publications were further analyzed. Where possible, a meta-analysis was performed using effect sizes (ES) calculated from discrete variables. In total, 41 publications examining 20 variables were included. The majority of consistent gait deviations associated with KOA were exhibited by those with severe disease in the temporospatial domain. Individuals with severe KOA exhibited greater stride duration than controls (ES 1.35 [95% confidence interval (95% CI) 1.03, 1.67]) and a decrease in cadence (ES -0.75 [95% CI -1.12, -0.39]) compared with controls. The evidence for kinematic and joint moment change was primarily limited or conflicting. There was a lack of evidence for alterations in the external knee adduction moment. Individuals with KOA exhibit a range of gait deviations compared with controls. Despite its common usage in KOA gait studies, we did not find consistent evidence that knee adduction moment differs between those with and without KOA or between disease severity levels. Further research examining the reasons for a lack of difference in many gait variables in those with knee OA is needed. Copyright © 2013 by the American College of Rheumatology.

Summed and Weighted Summary Scores for the Medsger Disease Severity Scale Compared with the Physician's Global Assessment of Disease Severity in Systemic Sclerosis.

PubMed

Harel, Daphna; Hudson, Marie; Iliescu, Alexandra; Baron, Murray; Steele, Russell

2016-08-01

To develop a weighted summary score for the Medsger Disease Severity Scale (DSS) and to compare its measurement properties with those of a summed DSS score and a physician's global assessment (PGA) of severity score in systemic sclerosis (SSc). Data from 875 patients with SSc enrolled in a multisite observational research cohort were extracted from a central database. Item response theory was used to estimate weights for the DSS weighted score. Intraclass correlation coefficients (ICC) and convergent, discriminative, and predictive validity of the 3 summary measures in relation to patient-reported outcomes (PRO) and mortality were compared. Mean PGA was 2.69 (SD 2.16, range 0-10), mean DSS summed score was 8.60 (SD 4.02, range 0-36), and mean DSS weighted score was 8.11 (SD 4.05, range 0-36). ICC were similar for all 3 measures [PGA 6.9%, 95% credible intervals (CrI) 2.1-16.2; DSS summed score 2.5%, 95% CrI 0.4-6.7; DSS weighted score 2.0%, 95% CrI 0.1-5.6]. Convergent and discriminative validity of the 3 measures for PRO were largely similar. In Cox proportional hazards models adjusting for age and sex, the 3 measures had similar predictive ability for mortality (adjusted R(2) 13.9% for PGA, 12.3% for DSS summed score, and 10.7% DSS weighted score). The 3 summary scores appear valid and perform similarly. However, there were some concerns with the weights computed for individual DSS scales, with unexpected low weights attributed to lung, heart, and kidney, leading the PGA to be the preferred measure at this time. Further work refining the DSS could improve the measurement properties of the DSS summary scores.

Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

PubMed

Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

2018-03-01

Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

Mannose Binding Lectin Is Required for Alphavirus-Induced Arthritis/Myositis

PubMed Central

Whitmore, Alan C.; Blevins, Lance K.; Hueston, Linda; Fraser, Robert J.; Herrero, Lara J.; Ramirez, Ruben; Smith, Paul N.; Mahalingam, Suresh; Heise, Mark T.

2012-01-01

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3−/− mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis. PMID:22457620

A rapid echocardiographic screening protocol for rheumatic heart disease in Samoa: a high prevalence of advanced disease.

PubMed

Allen, Marvin; Allen, John; Naseri, Take; Gardner, Rebecca; Tolley, Dennis; Allen, Lori

2017-10-01

Echocardiography has been proposed as a method to screen children for rheumatic heart disease. The World Heart Federation has established guidelines for echocardiographic screening. In this study, we describe a rapid echocardiogram screening protocol according to the World Heart Federation guidelines in Samoa, endemic for rheumatic heart disease. We performed echocardiogram screening in schoolchildren in Samoa between 2013 and 2015. A brief screening echocardiogram was performed on all students. Children with predefined criteria suspicious for rheumatic hear diseases were referred for a more comprehensive echocardiogram. Complete echocardiograms were classified according to the World Heart Federation guidelines and severity of valve disease. Echocardiographic screening was performed on 11,434 children, with a mean age of 10.2 years; 51% of them were females. A total of 558 (4.8%) children underwent comprehensive echocardiography, including 49 students who were randomly selected as controls. Definite rheumatic heart disease was observed in 115 students (10.0 per 1000): 92 students were classified as borderline (8.0 per 1000) and 23 with CHD. Advanced disease was identified in 50 students (4.4 per 1000): 15 with severe mitral regurgitation, five with severe aortic regurgitation, 11 with mitral stenoses, and 19 with mitral and aortic valve disease. We successfully applied a rapid echocardiographic screening protocol to a large number of students over a short time period - 28 days of screening over a 3-year time period - to identify a high prevalence of rheumatic heart disease. We also reported a significantly higher rate of advanced disease compared with previously published echocardiographic screening programmes.

Protein-energy wasting significantly increases healthcare utilization and costs among patients with chronic kidney disease: a propensity-score matched cohort study.

PubMed

Chao, Chia-Ter; Tang, Chao-Hsiun; Cheng, Rhoda Wen-Yi; Wang, Michael Yao-Hsien; Hung, Kuan-Yu

2017-09-01

Disease-related malnutrition is highly prevalent, and has prognostic implications for patients with chronic kidney disease (CKD); however, few studies have investigated the impact of malnutrition, or protein-energy wasting (PEW), on healthcare utilization and medical expenditure among CKD patients. Using claim data from the National Health Insurance in Taiwan, this study identified patients with CKD between 2009-2013 and categorized them into those with mild, moderate, or severe CKD. Cases with PEW after CKD was diagnosed were propensity-score matched with controls in a 1:4 ratio. Healthcare resource utilization metrics were compared, including outpatient and emergency department visits, frequency and duration of hospitalization, and the cumulative costs associated with different CKD severity. From among 347,501 CKD patients, eligible cohorts of 66,872 with mild CKD (49.2%), 27,122 with moderate CKD (19.9%), and 42,013 with severe CKD (30.9%) were selected. Malnourished CKD patients had significantly higher rates of hospitalization (p < .001 for all severities) and re-admission (p = .015 for mild CKD, p = .002 for severe CKD) than non-malnourished controls. Cumulative medical costs for outpatient and emergency visits, and hospitalization, were significantly higher among all malnourished CKD patients than non-malnourished ones (p < .001); total medical costs were also higher among malnourished patients with mild (62.9%), moderate (59.6%), or severe (43.6%) CKD compared to non-malnourished patients (p < .001). In a nationally-representative cohort, CKD patients with PEW had significantly more healthcare resource utilization and higher aggregate medical costs than those without, across the spectrum of CKD: preventing PEW in CKD patients should receive high priority if we would like to reduce medical costs.

Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea

PubMed Central

Tickell, Kirkby D.; Pavlinac, Patricia B.; John-Stewart, Grace C.; Denno, Donna M.; Richardson, Barbra A.; Naulikha, Jaqueline M.; Kirera, Ronald K.; Swierczewski, Brett E.; Singa, Benson O.; Walson, Judd L.

2017-01-01

Abstract. Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6–59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ −2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P < 0.01), and enteroaggregative Escherichia coli recovered from their stool (aPR: 1.8, 1.1–2.8, P = 0.02). There were no differences in the prevalence of other pathogens by wasting status after confounder adjustment. Stunting was not associated with clinical severity or the presence of specific pathogens. Wasted children with diarrhea presented with more severe disease than children without malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children. PMID:29140236

Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea.

PubMed

Tickell, Kirkby D; Pavlinac, Patricia B; John-Stewart, Grace C; Denno, Donna M; Richardson, Barbra A; Naulikha, Jaqueline M; Kirera, Ronald K; Swierczewski, Brett E; Singa, Benson O; Walson, Judd L

2017-11-01

Children with acute and chronic malnutrition are at increased risk of morbidity and mortality following a diarrheal episode. To compare diarrheal disease severity and pathogen prevalence among children with and without acute and chronic malnutrition, we conducted a cross-sectional study of human immunodeficiency virus-uninfected Kenyan children aged 6-59 months, who presented with acute diarrhea. Children underwent clinical and anthropometric assessments and provided stool for bacterial and protozoal pathogen detection. Clinical and microbiological features were compared using log binomial regression among children with and without wasting (mid-upper arm circumference ≤ 125 mm) or stunting (height-for-age z score ≤ -2). Among 1,363 children, 7.0% were wasted and 16.9% were stunted. After adjustment for potential confounders, children with wasting were more likely than nonwasted children to present with at least one Integrated Management of Childhood Illness danger sign (adjusted prevalence ratio [aPR]: 1.3, 95% confidence interval [CI]: 1.0 to 1.5, P = 0.05), severe dehydration (aPR: 2.4, 95% CI: 1.5 to 3.8, P < 0.01), and enteroaggregative Escherichia coli recovered from their stool (aPR: 1.8, 1.1-2.8, P = 0.02). There were no differences in the prevalence of other pathogens by wasting status after confounder adjustment. Stunting was not associated with clinical severity or the presence of specific pathogens. Wasted children with diarrhea presented with more severe disease than children without malnutrition which may be explained by a delay in care-seeking or diminished immune response to infection. Combating social determinants and host risk factors associated with severe disease, rather than specific pathogens, may reduce the disparities in poor diarrhea-associated outcomes experienced by malnourished children.

Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis

PubMed Central

Fiorucci, S; Orlandi, S; Mencarelli, A; Caliendo, G; Santagada, V; Distrutti, E; Santucci, L; Cirino, G; Wallace, J L

2007-01-01

Background and Purpose: Mesalamine is the first-line therapy for colitis, but it lacks potency and is only effective for mild-to-moderate forms of this disease. Hydrogen sulphide has been shown to be a potent, endogenous anti-inflammatory substance, modulating leukocyte-endothelial adhesion and leukocyte migration. The purpose of this study was to determine if an H2S-releasing derivative of mesalamine (ATB-429) would exhibit increased potency and effectiveness in a mouse model of colitis. Experimental Approach: Colitis was induced in mice with trinitrobenzene sulphonic acid and the effects of ATB-429 and mesalamine were compared in several treatment regimens. The severity of colitis was determined using several indices, including a disease activity score (comprised of scores for diarrhea, weight loss and fecal blood), colonic myeloperoxidase activity and macroscopic/microscopic scoring of tissue injury. Key Results: Irrespective of the treatment regiment, ATB-429 was more effective than mesalamine in reducing the severity of colitis. ATB-429 was particularly effective in reducing granulocyte infiltration into the colonic tissue (by ∼70%), as well as reducing the expression of mRNA for several key proinflammatory cytokines/chemokines (e.g., TNFα, IFNγ). Treatment with ADT-OH, the H2S-releasing moiety of ATB-429, did not affect severity of colitis. Conclusions and Implications: ATB-429 exhibits a marked increase in anti-inflammatory activity and potency in a murine model of colitis, as compared to mesalamine. These results are consistent with recently described anti-inflammatory effects of H2S. ATB-429 may represent an attractive alternative to mesalamine for the treatment of inflammatory bowel disease. PMID:17339831

Gender differences in disease activity and clinical features in newly diagnosed systemic lupus erythematosus patients.

PubMed

Muñoz-Grajales, C; González, L A; Alarcón, G S; Acosta-Reyes, J

2016-10-01

The objective of this paper is to compare disease activity and clinical features at diagnosis in male and female patients with systemic lupus erythematosus (SLE). This was a cross-sectional study in which every male patient (n = 40) was matched with three female patients of the same age (±5 years) and racial/ethnic group; disease activity as per the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and disease manifestations at the time of diagnosis were compared. Alopecia and anti-Ro antibodies were more frequent in female patients. No statistically significant difference in any other disease characteristics was found. However, male gender was associated with a risk of severe disease activity at the time of diagnosis (as determined by SLEDAI ≥12 score) independent of age, racial/ethnic group, anti-Ro positivity or time to criteria accrual (OR: 3.11 95% CI, 1.09-8.92; p = 0.035). In newly diagnosed SLE patients, male gender is associated with higher disease activity despite the fact that male and female patients seem to experience similar overall disease manifestations. © The Author(s) 2016.

Active matrix metalloproteinase-8 and periodontal bacteria depending on periodontal status in patients with rheumatoid arthritis.

PubMed

Kirchner, A; Jäger, J; Krohn-Grimberghe, B; Patschan, S; Kottmann, T; Schmalz, G; Mausberg, R F; Haak, R; Ziebolz, D

2017-08-01

The aim of this clinical cross-sectional study was to determine the level of active matrix metalloproteinase-8 (aMMP-8) and periodontal pathogenic bacteria in gingival crevicular fluid in patients with rheumatoid arthritis (RA) with varying periodontal conditions. In total, 103 patients with RA and 104 healthy controls (HC) were included. The assessment of periodontal status included periodontal probing depth, bleeding on probing and clinical attachment loss. Periodontal disease was classified as healthy/mild, moderate or severe. For the determination of aMMP-8 levels using enzyme-linked immunosorbent assay and periodontal pathogenic bacteria using polymerase chain reaction, samples of gingival crevicular fluid were taken from the deepest gingival pockets. The statistical analyses used included a Mann-Whitney U-test, a chi-squared test or a Fisher's exact test, and the significance level was set at α = 5%. We found that 65% of patients with RA and 79% of HC had moderate to severe periodontal disease (p = 0.02). The prevalence of periodontal pathogens was almost equal (p > 0.05). Furthermore, depending on periodontal disease severity only minor differences in bacterial prevalence were detected. With increasing severity of periodontal disease, higher aMMP-8 levels were observed. Accordingly, a significant difference in patients with moderate periodontal disease (RA: 15.3 ± 13.8; HC: 9.1 ± 9.1; p ≤ 0.01) and severe periodontal disease (RA: 21.7 ± 13.3; HC: 13.1 ± 8.6; p = 0.07) was detected, with a greater tendency in the latter group. The increased aMMP-8 levels in the RA group indicate that the presence of RA appears to have an influence on the host response at a comparable level of bacterial load and periodontal disease severity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical results with beta-methyl-p-(123I)iodophenylpentadecanoic acid, single-photon emission computed tomography in cardiac disease.

PubMed

Nishimura, T; Uehara, T; Shimonagata, T; Nagata, S; Haze, K

1994-01-01

This study was undertaken to evaluate the relationships, between myocardial perfusion and metabolism. Simultaneous beta-methyl-p(123I)iodophenylpentadecanoic acid (123I-BMIPP) and thallium 201 myocardial single-photon emission computed tomography (SPECT) were performed in 25 patients with myocardial infarction (group A) and 16 patients with hypertrophic cardiomyopathy (group B). The severity scores of 123I-BMIPP and 201Tl myocardial SPECT images were evaluated semiquantitatively by segmental analysis. In Group A, dissociations between thallium- and 123I-BMIPP-imaged defects were frequently observed in patients with successful reperfusion compared with those with no reperfusion and those with reinfarction. In four patients with successful reperfusion, repeated 123I-BMIPP and 201Tl myocardial SPECT showed gradual improvement of the 123I-BMIPP severity score compared with the thallium severity score. In group B, dissociations between thallium- and 123I-BMIPP-imaged defects were also demonstrated in hypertrophic myocardium. In addition, nonhypertrophic myocardium also had decreased 123I-BMIPP uptake. In groups A and B, 123I-BMIPP severity scores correlated well with left ventricular function compared with thallium severity scores. These findings indicate that 123I-BMIPP is a suitable agent for the assessment of functional integrity, because left ventricular wall motion is energy dependent and 123I-BMIPP may reflect an aspect of myocardial energy production. This agent may be useful for the early detection and patient management of various heart diseases as an alternative to positron emission tomographic study.

Does minimalist transfemoral transcatheter aortic valve replacement produce better survival in patients with severe chronic obstructive pulmonary disease?

PubMed

Condado, Jose F; Haider, Moosa N; Lerakis, Stamatios; Keegan, Patricia; Caughron, Hope; Thourani, Vinod H; Devireddy, Chandan; Leshnower, Bradley; Mavromatis, Kreton; Sarin, Eric L; Stewart, James; Guyton, Robert; Forcillo, Jessica; Patel, Ateet; Simone, Amy; Block, Peter C; Babaliaros, Vasilis

2017-03-01

To compare outcomes after minimalist and standard transfemoral transcatheter aortic valve replacement (TF-TAVR) in patients with severe chronic obstructive pulmonary disease (COPD). TF-TAVR is increasingly performed with conscious sedation and transthoracic echocardiography guidance (minimalist). The safety/efficacy of this technique in patients with severe COPD is unknown. We compared demographics, 30-day outcomes and 1-year survival of patients with severe COPD (FEV1% ≤50) who underwent minimalist vs. standard TF-TAVR between 2008 and 2015 at our institution. Of 88 patients with severe COPD, 46 underwent minimalist and 42 underwent standard TF-TAVR. There were no differences on baseline characteristics, except for more history of coronary artery bypass grafting (45.5% vs. 20.6%, P = 0.03) and less history of cerebrovascular disease (16.7% vs. 45.5%, P = 0.03) in the standard TF-TAVR. Seventeen minimalist TF-TAVR patients (41.0%) were transferred directly to the general medical ward with telemetry monitoring (without ICU stay); all standard TF-TAVR patients went to the ICU. Minimalist TF-TAVR patients had shorter procedure time (97 vs. 129 min, P < 0.001), ICU time (21.8 vs. 29.8 hr, P = 0.001) and length of stay (2 vs. 5 days, P = 0.001). There were no differences in procedure complications and 30-day mortality between groups. In our multivariate analysis, minimalist TF-TAVR (HR 0.28, 95%CI 0.08-0.97) and previous coronary revascularization (HR 0.24, 95%CI 0.09-0.65) were associated with increased 1-year survival. In contrast, moderate paravalvular leak (HR 7.73, 95%CI 1.94-30.84) was associated with decreased 1-year survival. In patients with severe COPD, Minimalist TF-TAVR results in less resource utilization and improved 1-year survival compared to standard approach. Our findings should be validated in a larger cohort of patients with severe COPD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

To Control False Positives in Gene-Gene Interaction Analysis: Two Novel Conditional Entropy-Based Approaches

PubMed Central

Lin, Meihua; Li, Haoli; Zhao, Xiaolei; Qin, Jiheng

2013-01-01

Genome-wide analysis of gene-gene interactions has been recognized as a powerful avenue to identify the missing genetic components that can not be detected by using current single-point association analysis. Recently, several model-free methods (e.g. the commonly used information based metrics and several logistic regression-based metrics) were developed for detecting non-linear dependence between genetic loci, but they are potentially at the risk of inflated false positive error, in particular when the main effects at one or both loci are salient. In this study, we proposed two conditional entropy-based metrics to challenge this limitation. Extensive simulations demonstrated that the two proposed metrics, provided the disease is rare, could maintain consistently correct false positive rate. In the scenarios for a common disease, our proposed metrics achieved better or comparable control of false positive error, compared to four previously proposed model-free metrics. In terms of power, our methods outperformed several competing metrics in a range of common disease models. Furthermore, in real data analyses, both metrics succeeded in detecting interactions and were competitive with the originally reported results or the logistic regression approaches. In conclusion, the proposed conditional entropy-based metrics are promising as alternatives to current model-based approaches for detecting genuine epistatic effects. PMID:24339984

Neuromuscular electrical stimulation versus traditional therapy in patients with Parkinson's disease and oropharyngeal dysphagia: effects on quality of life.

PubMed

Heijnen, B J; Speyer, R; Baijens, L W J; Bogaardt, H C A

2012-09-01

This study compares the effects of traditional logopedic dysphagia treatment with those of neuromuscular electrical stimulation (NMES) as adjunct to therapy on the quality of life in patients with Parkinson's disease and oropharyngeal dysphagia. Eighty-eight patients were randomized over three treatment groups. Traditional logopedic dysphagia treatment and traditional logopedic dysphagia treatment combined with NMES at sensor or motor level stimulation were compared. At three times (pretreatment, post-treatment, and 3 months following treatment), two quality-of-life questionnaires (SWAL-QOL and MD Anderson Dysphagia Inventory) and a single-item Dysphagia Severity Scale were scored. The Functional Oral Intake Scale was used to assess the dietary intake. After therapy, all groups showed significant improvement on the Dysphagia Severity Scale and restricted positive effects on quality of life. Minimal group differences were found. These effects remained unchanged 3 months following treatment. No significant correlations were found between dietary intake and quality of life. Logopedic dysphagia treatment results in a restricted increased quality of life in patients with Parkinson's disease. In this randomized controlled trial, all groups showed significant therapy effects on the Dysphagia Severity Scale and restricted improvements on the SWAL-QOL and the MDADI. However, only slight nonsignificant differences between groups were found.

Clinical and MRI characterization of MS patients with a pure and severe cognitive onset.

PubMed

Assouad, Rana; Louapre, Celine; Tourbah, Ayman; Papeix, Caroline; Galanaud, Damien; Lubetzki, Catherine; Stankoff, Bruno

2014-11-01

Cognitive and behavioural symptoms are common in multiple sclerosis (MS), but they are rarely the inaugural and predominant manifestation of the disease. Our objective is to characterize the clinical and radiological features of cognitive-multiple sclerosis (cog-MS), defined as MS subjects who entered into the disease with cognitive symptoms, which subsequently remain the predominant manifestation. We describe the disease course, and clinical and radiological features of 18 subjects with a cognitive form of MS. Memory loss and behavioural changes were the primary symptoms at disease onset. They remained prominent and led to severe cognitive impairment during disease course. The main associated manifestations were depression, pathological laughing and/or crying, urinary incontinence and gait disturbance suggestive of high-level gait disorder. Motor, sensory or cerebellar abnormalities were uncommon. During disease course, superimposed neurological relapses occurred in 61% of cases. Brain MRI revealed multiple periventricular lesions that were extensive and confluent in half of cases, and a severe atrophy measured as an increase in the third ventricular width compared to age-matched healthy controls. Gadolinium-enhancing lesions were common (72%). The mean diagnosis delay from disease onset was 2 years. A principal component analysis on the neuropsychological results revealed that verbal memory assessment is complementary to global cognitive functioning evaluation in these patients with severe cognitive deficit. Verbal memory deficit was associated with high EDSS. cog-MS patients might represent a challenging diagnosis, which needs to be individualized for an early management. Copyright © 2014 Elsevier B.V. All rights reserved.

B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss.

PubMed

Al Dhaibani, Muna A; El-Hattab, Ayman W; Ismayl, Omar; Suleiman, Jehan

2018-05-23

Mutations in B3GALNT2 , encoding a glycosyltransferase enzyme involved in α-dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2 -related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle-eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2 . The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker-Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2 -related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2 -related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype-phenotype correlation in these cases. Georg Thieme Verlag KG Stuttgart · New York.

Periodontal disease, tooth loss and colorectal cancer risk: Results from the Nurses' Health Study.

PubMed

Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A; Ogino, Shuji; Chan, Andrew T; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S; Stampfer, Meir J; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

2017-02-01

Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses' Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25-32 teeth, the multivariable HR (95% CI) for CRC for women with <17 teeth was 1.20 (1.04-1.39). With regard to tumor site, the HRs (95% CIs) for the same comparison were 1.23 (1.01-1.51) for proximal colon cancer, 1.03 (0.76-1.38) for distal colon cancer and 1.48 (1.07-2.05) for rectal cancer. In addition, compared to those without periodontal disease, HRs for CRC were 0.91 (95% CI 0.74-1.12) for periodontal disease, and 1.22 (95% CI 0.91-1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. © 2016 UICC.

Relationship between Cough-Associated Changes in CSF Flow and Disease Severity in Chiari I Malformation: An Exploratory Study Using Real-Time MRI.

PubMed

Bezuidenhout, A F; Khatami, D; Heilman, C B; Kasper, E M; Patz, S; Madan, N; Zhao, Y; Bhadelia, R A

2018-05-10

Currently no quantitative objective test exists to determine disease severity in a patient with Chiari I malformation. Our aim was to correlate disease severity in symptomatic patients with Chiari I malformation with cough-associated changes in CSF flow as measured with real-time MR imaging. Thirteen symptomatic patients with Chiari I malformation (tonsillar herniation of ≥5 mm) were prospectively studied. A real-time, flow-sensitized pencil-beam MR imaging scan was used to measure CSF stroke volume during rest and immediately following coughing and relaxation periods (total scan time, 90 seconds). Multiple posterior fossa and craniocervical anatomic measurements were also obtained. Patients were classified into 2 groups by neurosurgeons blinded to MR imaging measurements: 1) nonspecific Chiari I malformation (5/13)-Chiari I malformation with nonspecific symptoms like non-cough-related or mild occasional cough-related headache, neck pain, dizziness, paresthesias, and/or trouble swallowing; 2) specific Chiari I malformation (8/13)-patients with Chiari I malformation with specific symptoms and/or objective findings like severe cough-related headache, myelopathy, syringomyelia, and muscle atrophy. The Spearman correlation was used to determine correlations between MR imaging measurements and disease severity, and both groups were also compared using a Mann-Whitney U test. There was a significant negative correlation between the percentage change in CSF stroke volume (resting to postcoughing) and Chiari I malformation disease severity ( R = 0.59; P = .03). Mann-Whitney comparisons showed the percentage change in CSF stroke volume (resting to postcoughing) to be significantly different between patient groups ( P = .04). No other CSF flow measurement or anatomic measure was significantly different between the groups. Our exploratory study suggests that assessment of CSF flow response to a coughing challenge has the potential to become a valuable objective noninvasive test for clinical assessment of disease severity in patients with Chiari I malformation. © 2018 by American Journal of Neuroradiology.

Streptococcus mitis Strains Causing Severe Clinical Disease in Cancer Patients

PubMed Central

Sahasrabhojane, Pranoti; Saldana, Miguel; Yao, Hui; Su, Xiaoping; Horstmann, Nicola; Thompson, Erika; Flores, Anthony R.

2014-01-01

The genetically diverse viridans group streptococci (VGS) are increasingly recognized as the cause of a variety of human diseases. We used a recently developed multilocus sequence analysis scheme to define the species of 118 unique VGS strains causing bacteremia in patients with cancer; Streptococcus mitis (68 patients) and S. oralis (22 patients) were the most frequently identified strains. Compared with patients infected with non–S. mitis strains, patients infected with S. mitis strains were more likely to have moderate or severe clinical disease (e.g., VGS shock syndrome). Combined with the sequence data, whole-genome analyses showed that S. mitis strains may more precisely be considered as >2 species. Furthermore, we found that multiple S. mitis strains induced disease in neutropenic mice in a dose-dependent fashion. Our data define the prominent clinical effect of the group of organisms currently classified as S. mitis and lay the groundwork for increased understanding of this understudied pathogen. PMID:24750901

Medical Management of Crohn Disease

PubMed Central

Scott, Frank I.; Osterman, Mark T.

2013-01-01

Crohn disease (CD) is one of the major subtypes of inflammatory bowel disease and can occur in any segment of the alimentary tract. There have been significant advances in the medical therapy of CD over the past several decades. For mild CD, the oral corticosteroid derivative budesonide has demonstrated superior efficacy compared with traditional therapies such as 5-aminosalicylic acid, and can be used concurrently with these agents. For the management of moderate to severe disease, the immunomodulators azathioprine, 6-mercaptopurine, and methotrexate, as well as the antitumor necrosis factor-alpha (TNF-α) agents infliximab, adalimumab, and certolizumab pegol, have become the mainstay of therapy, with growing interest in combining these agents for maximal effect. Immunomodulators and anti-TNF-α agents have also demonstrated benefit in fistulizing CD. There has been growing evidence suggesting that both of these agents, along with the antibiotics metronidazole and ornidazole, are also effective in preventing postoperative recurrence of CD. PMID:24436652

Relationship between sleep quality and mental health according to demographics of 850 patients with chronic obstructive pulmonary disease.

PubMed

Eslaminejad, Alireza; Safa, Mitra; Ghassem Boroujerdi, Fatemeh; Hajizadeh, Farzaneh; Pashm Foroush, Maryam

2017-10-01

We aimed to study sleep problems in hospitalized chronic obstructive pulmonary disease patients and assess the relationship of sleep quality with mental health and demographics of patients. Our study sample consisted of 850 chronic obstructive pulmonary disease patients hospitalized in Masih Daneshvari Hospital. Demographic data were collected and the Pittsburgh Sleep Quality and mental health questionnaires were filled out for patients. The results showed that 5.9 percent were suffering from severe sleep problems, while 4.7 percent had severe mental problems. A strong positive correlation was found between the total scores of mental health and sleep quality ( p < 0.01). The prevalence of sleep and mental health problems was higher in females compared to males. Mental health and sleep quality play important roles in quality of life of chronic obstructive pulmonary disease patients.

A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans

PubMed Central

Kim, Hye Young; Eyheramonho, María Belén; Pichavant, Muriel; Gonzalez Cambaceres, Carlos; Matangkasombut, Ponpan; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Konduru, Krishnamurthy; Manangeeswaran, Mohanraj; Freeman, Gordon J.; Kaplan, Gerardo G.; DeKruyff, Rosemarie H.; Umetsu, Dale T.; Rosenzweig, Sergio D.

2011-01-01

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy. PMID:21339644

On the significance of electroconvulsive therapy in the treatment of severe mental diseases.

PubMed

Grözinger, Michael; Smith, Elke Stefanie; Conca, Andreas

2015-04-01

Quite a few patients with severe mental diseases do not respond sufficiently to psychopharmacology and psychotherapy. For some of these, electroconvulsive therapy (ECT) offers a promising alternative. Erroneously, the method is being perceived as old fashioned by the lay public, but also by many doctors. Therefore, this overview aims at all colleagues who in their role as multipliers, referring physicians or ECT specialists can reduce the likelihood of mental disease to become chronic. During the last decades, numerous international medical societies including the Austrian and the German Association for Psychiatry (ÖGPP and DGPPN) have pointed to the importance of ECT as a modern medical intervention. Our overview is based on these guidelines and statements. Additionally selective literature searches have been conducted concerning some key aspects. Due to its excellent efficacy, ECT is an important option in the treatment of severe mental disease. Technological innovations and continued development in the psychiatric environment determined the evolution from the electroshock of the 1930s to the ECT of today. This process led to reduced side effects and a stronger patient-oriented praxis. ECT is a modern, highly effective and safe treatment of severe mental diseases with comparatively few side effects. The method should not be used as a last resort but in an evidence-based way. Patients should be informed timely and adequately about the therapeutic option.

A Retrospective Review of Treatment Results for Patients With Central Centrifugal Cicatrical Alopecia.

PubMed

Eginli, Ariana; Dothard, Emily; Bagayoko, Courtney W; Huang, Karen; Daniel, Alyssa; McMichael, Amy J

2017-04-01

INTRODUCTION: Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia primarily affecting women of African descent on the crown of the scalp. Limited data exists regarding evidence-based treatment for CCCA.

OBJECTIVE: To examine photos of subjects with CCCA before and after treatment in order to evaluate results of treatment and compare results of different treatment regimens.

METHODS: Photographs of 15 subjects with CCCA before and after treatment were evaluated by two blinded investigators who assigned disease severity scores to photographs based on a published scale: Central Scalp Alopecia Photographic Scale in African American Women.

RESUTLS: Median change in severity score (post-treatment severity score - pre-treatment severity score) was 0.5 (P = 0.58) for all 15 subjects receiving a series of 7 to 8 intralesional steroid injections along with topical steroids (Class I/II) +/- minoxidil and +/- anti-dandruff shampoo, indicating worsening of disease after treatment. Subjects receiving minoxidil versus those who did not (0.25 vs 0.5; P = 0.38) and subjects receiving anti-dandruff shampoo versus those who did not (0.0 vs 0.5; P = 0.42) demonstrated no statistically significant difference in pre- and post-treatment severity scores. Of 15 subjects, 5/15 (33.3%) had decreased severity scores, 8/15 (53.3%) had increased severity scores, and 2/15 (13.3%) had no change in severity scores.

CONCLUSIONS: Although no statistically significant difference was found in pre- versus post-treatment disease severity, this may indicate intralesional steroid injections and topical steroids +/- minoxidil and +/- anti-dandruff shampoo halt disease progression.

J Drugs Dermatol. 2017;16(4):317-320.

Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population.

PubMed

Wiatrak, Brian J; Wiatrak, Deborah W; Broker, Thomas R; Lewis, Linda

2004-11-01

A database was developed for prospective, longitudinal study of recurrent respiratory papillomatosis (RRP) in a large population of pediatric patients. Data recorded for each patient included epidemiological factors, human papilloma virus (HPV) type, clinical course, staged severity of disease at each surgical intervention, and frequency of surgical intervention. The study hypothesizes that patients with HPV type 11 (HPV-11) and patients younger than 3 years of age at diagnosis are at risk for more aggressive and extensive disease. The 10-year prospective epidemiological study used disease staging for each patient with an original scoring system. Severity scores were updated at each surgical procedure. Parents of children with RRP referred to the authors' hospital completed a detailed epidemiological questionnaire at the initial visit or at the first return visit after the study began. At the first endoscopic debridement after study enrollment, tissue was obtained and submitted for HPV typing using polymerase chain reaction techniques and in situ hybridization. Staging of disease severity was performed in real time at each endoscopic procedure using an RRP scoring system developed by one of the authors (B.J.W.). The frequency of endoscopic operative debridement was recorded for each patient. Information in the database was analyzed to identify statistically significant relationships between extent of disease and/or HPV type, patient age at diagnosis, and selected epidemiological factors. The study may represent the first longitudinal prospective analysis of a large pediatric RRP population. Fifty-eight of the 73 patients in the study underwent HPV typing. Patients infected with HPV-11 were significantly more likely to have higher severity scores, require more frequent surgical intervention, and require adjuvant therapy to control disease progression. In addition, patients with HPV-11 RRP were significantly more likely to develop tracheal disease, to require tracheotomy, and to develop pulmonary disease. Patients receiving a diagnosis of RRP before 3 years of age had significantly higher severity scores, higher frequencies of surgical intervention, and greater likelihood of requiring adjuvant medical therapy. Patients with Medicaid insurance had significantly higher severity scores and required more frequent surgical debridement. Birth by cesarean section appeared to be a significant risk factor for more severe disease and necessity of more frequent surgical intervention. Statistical analysis of the relationships among epidemiological factors, HPV type, and clinical course revealed that patients with HPV-11 and patients younger than 3 years of age at RRP diagnosis are prone to develop more aggressive disease as represented by higher severity scores at endoscopic debridement, more frequent operative debridement procedures per year, a greater requirement for adjuvant therapy, and greater likelihood of tracheal disease with tracheotomy.

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts

PubMed Central

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-01-01

Introduction Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. Methods We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. Results The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in ‘severe’ patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. Conclusion The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity. PMID:27516225

Relevance of Non-communicable Comorbidities for the Development of the Severe Forms of Dengue: A Systematic Literature Review.

PubMed

Toledo, Joao; George, Leyanna; Martinez, Eric; Lazaro, Adhara; Han, Wai Wai; Coelho, Giovanini E; Runge Ranzinger, Silvia; Horstick, Olaf

2016-01-01

Patients with dengue fever and comorbidities seem to be at higher risk of developing complications and/or severe dengue compared to healthier individuals. This study systematically reviews the evidence related to comorbidities and dengue. A systematic literature review was performed in five databases (EMBASE, PUBMED, Global Health, SciELO, Cochrane) and grey literature for full-text articles since its inceptions until October 10, 2015. A total of 230 articles were retrieved. Sixteen studies were analysed after applying all inclusion and exclusion criteria. Seven case control studies and nine retrospective cohort studies showed that comorbidities may contribute to severe dengue, especially 1) cardiovascular disease, 2) stroke, 3) diabetes, 4) respiratory disease and 5) renal disease, as well as old age. However, due to heterogeneity in studies, the real estimate effect of comorbidities as modifiers of dengue severity could not be established. Further research in regions with high prevalence of dengue infection would contribute to a better understanding of the relevance of comorbidities in severe dengue, especially with a standardised protocol, for outcomes, specific comorbidities, study design-best using prospective designs-and sample sizes.

Impact of the severity of end-stage liver disease in cardiac structure and function.

PubMed

Silvestre, Odilson Marcos; Bacal, Fernando; de Souza Ramos, Danusa; Andrade, Jose L; Furtado, Meive; Pugliese, Vincenzo; Belleti, Elisangela; Andraus, Wellington; Carrilho, Flair José; Carneiro D'Albuquerque, Luiz Augusto; Queiroz Farias, Alberto

2013-01-01

The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD ≥ 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. Changes in cardiac structure and function correlate with the severity of ESLD.

Self-Reported Pain Intensity with the Numeric Reporting Scale in Adult Dengue

PubMed Central

Wong, Joshua G. X.; Gan, Victor C.; Ng, Ee-Ling; Leo, Yee-Sin; Chan, Siew-Pang; Choo, Robin; Lye, David C.

2014-01-01

Background Pain is a prominent feature of acute dengue as well as a clinical criterion in World Health Organization guidelines in diagnosing dengue. We conducted a prospective cohort study to compare levels of pain during acute dengue between different ethnicities and dengue severity. Methods Demographic, clinical and laboratory data were collected. Data on self-reported pain was collected using the 11-point Numerical Rating Scale. Generalized structural equation models were built to predict progression to severe disease. Results A total of 499 laboratory confirmed dengue patients were recruited in the Prospective Adult Dengue Study at Tan Tock Seng Hospital, Singapore. We found no statistically significant differences between pain score with age, gender, ethnicity or the presence of co-morbidity. Pain score was not predictive of dengue severity but highly correlated to patients’ day of illness. Prevalence of abdominal pain in our cohort was 19%. There was no difference in abdominal pain score between grades of dengue severity. Conclusion Dengue is a painful disease. Patients suffer more pain at the earlier phase of illness. However, pain score cannot be used to predict a patient’s progression to severe disease. PMID:24788828

Homocysteine, endothelin-1 and nitric oxide in patients with hypertensive disorders complicating pregnancy.

PubMed

Zeng, Yachang; Li, Mujun; Chen, Yue; Wang, Sumei

2015-01-01

To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP. Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay. Serum Hcy and ET-1 in HDCP group were significantly higher as compared to control group (P<0.05). Level of serum NO in HDCP group was significantly lower than in the control group (P<0.05). Level of serum Hcy and ET-1 in mild and severe preeclampsia group were significantly higher as compared to control group, respectively (P<0.05). Level of serum NO in mild and severe preeclampsia group were significantly lower than in the control group' respectively (P<0.05). Level of serum Hcy and ET-1 in severe preeclampsia group were significantly higher as compared to mild preclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05). Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP.

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum

PubMed Central

Salameh, Habeeb; Hanayneh, Muhannad Al; Masadeh, Maen; Naseemuddin, Mohammed; Matin, Tasnia; Erwin, Angelika; Singal, Ashwani K.

2016-01-01

Abstract Background and Aims: Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16–1.85) and 2.76 (2.30–3.13), and were 1.75 (1.24–2.46) and 4.44 (2.92–6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90–6.13) and 5.05 (1.47–17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2–3 to grade 0–1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43–3.80), 1.80 (1.36–2.37), 1.66 (1.42–1.94), 1.58 (1.19–2.10), and 2.63 (1.87–3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions: PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD. PMID:27777887

Role of proneurotensin as marker of paediatric coeliac disease

PubMed Central

Torinsson Naluai, Å.; Agardh, D.

2016-01-01

Summary Neurotensin (NT) is a gut hormone functioning proinflammatory through nuclear factor kappa B (NF‐κB) and interleukin (IL)−8 secretion or anti‐inflammatory through epidermal growth factor receptors. NT mRNA is down‐regulated in duodenal biopsies of children with untreated coeliac disease. The aim of this study was to investigate if plasma pro‐NT levels correlated with the degree of intestinal mucosal damage and tissue transglutaminase autoantibody (tTGA) levels in children with coeliac disease. Fasting plasma samples from 96 children with coeliac disease and 89 non‐coeliac disease controls were analysed for NT precursor fragment pro‐NT 1–117 by a chemiluminometric immunoassay. Pro‐NT levels were compared with NT mRNA from duodenal biopsies, assessed previously with quantitative polymerase chain reaction (PCR). Illumina core exome arrays were used for human leucocyte antigen (HLA) typing and the Marsh criteria applied to score mucosal damage. Tissue TGA was measured by radio binding assay. A general linear model compared pro‐NT levels with diagnosis of coeliac disease, Marsh score and HLA DQ haplotype. Spearman's rank test was used to compare pro‐NT levels with tTGA, age and duodenal NT mRNA levels, respectively. Plasma pro‐NT levels were elevated in children with coeliac disease (median 23 pmol/l higher, P = 0·003) and in those with severe intestinal mucosal damage (median 24 pmol/l higher for ≥ Marsh 3b versus not, P = 0·0004). Pro‐NT levels correlated further with tTGA (r 2 = 0·22, P = 0·002), but not with duodenal NTS mRNA levels (r 2 = −0·12, P = 0·14). Pro‐NT was not associated with any of the HLA risk‐haplotypes. Elevated peripheral pro‐NT levels reflect more severe forms of active coeliac disease, indicating a potential role of NT in intestinal inflammation. PMID:27612962

Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

PubMed Central

Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

2012-01-01

Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

Validation of an Alzheimer’s disease assessment battery in Asian participants with mild to moderate Alzheimer’s disease

PubMed Central

Shen, Joan HQ; Shen, Qi; Yu, Holly; Lai, Jin-Shei; Beaumont, Jennifer L; Zhang, Zhenxin; Wang, Huali; Kim, Seong Yoon; Chen, Christopher; Kwok, Timothy; Wang, Shuu-Jiun; Lee, Dong Young; Harrison, John; Cummings, Jeffrey

2014-01-01

There is a lack of validated tools for assessing Alzheimer’s disease (AD) across Asia. This study evaluates the psychometric properties of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Neuropsychological Test Battery (NTB) in Asian participants. Participants with mild to moderate AD (n=251) and healthy controls (n=51) from Mainland China, Taiwan, Singapore, Hong Kong, and South Korea completed selected instruments at several time points. Test-retest reliability was better than 0.70 for all tests. AD participants performed significantly more poorly than controls on every score. Within the AD group, greater disease severity corresponded to significantly poorer performance. The AD group test performance worsened over time and there was a trend for worse performance in AD compared to healthy controls over time. The ADAS-Cog, DAD, and NTB are reliable, valid, and responsive measures in this population and could be used for clinical trials across Asian countries/regions. PMID:25628967

Graves' disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms.

PubMed

Trzepacz, P T; Klein, I; Roberts, M; Greenhouse, J; Levey, G S

1989-11-01

Assessment of disease severity for patients with hyperthyroidism involves clinical evaluation and laboratory testing. To determine if there is a correlation between symptoms and thyroid function test results, we prospectively studied hyperthyroid patients using a standardized symptom rating scale and serum thyroid function parameters. We examined 25 patients with untreated, newly diagnosed Graves' disease using the Hyperthyroid Symptom Scale (HSS) and serum levels of thyroxine (T4), triiodothyronine (T3) relative insulin area (RIA), and estimates of free thyroxine index (FTI). In addition, we compared thyroid hormone levels with standard measures of depression and anxiety in these patients. When regression analyses controlling for age were performed, none of these symptom ratings were associated with FTI or T3 RIA. The HSS was correlated with goiter size and anxiety ratings and was inversely correlated with age. The present study suggests that there is no relationship between the clinical assessment of disease severity and serum levels of thyroid hormone in untreated Graves' disease.

Differences in active range of motion measurements in the upper extremity of patients with writer's cramp compared with healthy controls.

PubMed

Srivanitchapoom, Prachaya; Shamim, Ejaz A; Diomi, Pierre; Hattori, Takaaki; Pandey, Sanjay; Vorbach, Sherry; Park, Jung E; Wu, Tianxia; Auh, Sungyoung; Hallett, Mark

Exploratory case-control study. Writer's cramp (WC) is a type of focal hand dystonia. The central nervous system plays a role in its pathophysiology, but abnormalities in the affected musculoskeletal components may also be relevant. We compared the active range of motion (ROM) in patients with WC and healthy volunteers (HVs) and correlated the findings with disease duration and severity. Affected limb joints were measured with goniometers. Patients were assessed at least 3 months after their last botulinum toxin (botulinum neurotoxin) injection, and strength was clinically normal. t tests were used to compare the ROMs of WC with matched HVs. The Spearman correlation coefficient assessed the relationship of active ROMs to the disease duration and handwriting subscore of the Dystonia Disability Scale. ROMs of D1 metacarpophalangeal (MCP) joint extension as well as D2 and D5 MCP flexion were significantly smaller in WC, and distal interphalangeal joint extension in D3 and D5 was significantly greater compared with HVs. There were negative correlations between D2 MCP flexion and disease duration and with Dystonia Disability Scale. Abnormalities in ROMs in WC were found. Severity and disease duration correlated with reduced D2 MCP flexion. This may be related to intrinsic biomechanical abnormalities, co-contraction of muscles, or a combination of subclinical weakness and atrophy from repeated botulinum neurotoxin injections. Hand biomechanical properties should not be ignored in the pathophysiology of WC. 2c. Copyright © 2016 Hanley & Belfus. All rights reserved.

The cost of care of systemic lupus erythematosus (SLE) in the UK: annual direct costs for adult SLE patients with active autoantibody-positive disease.

PubMed

Khamashta, M A; Bruce, I N; Gordon, C; Isenberg, D A; Ateka-Barrutia, O; Gayed, M; Donatti, C; Guillermin, A-L; Foo, J; Perna, A

2014-03-01

The aim of the Systemic LUpus Erythematosus Cost of Care In Europe (LUCIE) study was to evaluate the annual direct medical costs of managing adults with active autoantibody-positive disease on medication for SLE in secondary care. This paper presents the UK analyses only. A cost-of-illness study was conducted from the perspective of the National Health Service. Health resource utilization data were retrieved over a two-year period from four centres in England and unit cost data were taken from published sources. At baseline, 86 patients were included, 38 (44.2%) had severe SLE and 48 (55.8%) had non-severe SLE. The mean (SD) SELENA-SLEDAI score was 7.7 (5.7). The mean (SD) annual direct medical cost of was estimated at £3231 (£2333) per patient and was 2.2 times higher in patients with severe SLE compared with patients with non-severe SLE (p < 0.001). Multivariate model analyses showed that renal disease involvement (p = 0.0016) and severe flares (p = 0.0001) were associated with higher annual direct costs. Improvement of the overall stability of SLE and early intervention to minimize the impact of renal disease may be two approaches to mitigate the long-term direct cost of managing SLE patients in the UK.

Prediction of pelvic pathology in subfertile women with combined Chlamydia antibody and CA-125 tests.

PubMed

Penninx, Josien; Brandes, Monique; de Bruin, Jan Peter; Schneeberger, Peter M; Hamilton, Carl J C M

2009-12-01

Chlamydia antibody test (CAT) has been proposed to predict tubal disease. A correlation between CA-125 and the extent of endometriosis has been found by others. In this study we explored whether a combination of the two tests adds to the predictive value of the individual tests for predicting tubal disease or endometriosis. We also used the combination of tests as a new index test to screen for severe pelvic pathology. This retrospective study compares the findings of 240 laparoscopies with the serological test results. Findings were classified according to the existing ASRM scoring systems for adnexal adhesions, distal tubal occlusion and endometriosis. Severe pelvic pathology was defined as the presence of ASRM classes III and IV tubal disease or ASRM classes III and IV endometriosis. The predictive value was calculated for both tests separately and for the combined test. The combined test was positive if at least one test result was abnormal (CAT positive and/or CA-125 > or =35 IU/ml). 67/240 women had tubal disease, 81/240 had some degree of endometriosis. The odds ratios (ORs) of the CAT and the combined test to diagnose severe tubal disease were 6.6 (2.6-17.0) and 7.3 (2.9-19.3), respectively. The ORs of the CA-125 and the combined test to diagnose severe endometriosis were 15.6 (6.2-40.2) and 3.0 (1.2-8.0), respectively. Severe pelvic pathology was present in 65/240 women (27%). The ORs for severe pelvic pathology of the CAT, CA-125 and the combined test were 2.5 (1.4-5.3), 4.9 (1.9-9.6) and 6.6 (3.3-13.4), respectively. If the combined test was normal 15 out 131 women (11%) were shown to have severe pelvic pathology. The combined test adds hardly anything to the predictive value of CAT alone to diagnose severe tubal disease. The combined test is better than the CAT to predict severe pelvic pathology, but is not significantly better than the CA-125. If both the CAT and CA-125 are normal one could consider not performing a laparoscopy.

Emotional functioning of adolescents and adults with congenital heart disease: a meta-analysis.

PubMed

Jackson, Jamie L; Misiti, Brian; Bridge, Jeffrey A; Daniels, Curt J; Vannatta, Kathryn

2015-01-01

This study aimed to quantitatively compare findings of emotional functioning across studies of adolescents and adults with congenital heart disease (CHD) through meta-analysis. The current meta-analysis included 22 studies of adolescent and adult survivors of CHD who completed measures of emotional functioning. Effect sizes were represented by Hedge's g. Heterogeneity was calculated and possible moderators (i.e., lesion severity, age, study location, study quality) were examined. Overall, adolescent and adult survivors of CHD did not differ in emotional functioning from healthy controls or normative data. However, significant heterogeneity was found, and there was a trend for degree of lesion severity to moderate emotional functioning. Further analysis of lesion severity indicated that individuals with moderate lesions reported better emotional functioning than controls/normative data. Limitations in existing literature precluded examination of patient age as a moderator. Study location and quality did not explain a significant portion of the variance in effects. Findings suggest that differences in emotional functioning may exist across lesion severities, and individuals with moderately severe lesions are emotionally thriving. Given the diversity within CHD lesion classifications, future studies should include other indicators of disease severity, such as measures of morbidity, to determine how disease may affect emotional functioning among survivors of CHD. Furthermore, authors and journals need to ensure that research is reported in enough detail to facilitate meta-analysis, a critically important tool in answering discrepancies in the literature. © 2014 Wiley Periodicals, Inc.

The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Jafari Andarian, Saeideh; Olyaeemanesh, Alireza; Hosseini, Seyed Alireza; Akbari Sari, Ali; Firoozbakhsh, Shahram; Nouhi Jadesi, Mojtaba; Mobinizadeh, Mohammadreza

2016-01-01

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, which reduces the lung function and causes respiratory symptoms over time, and it is primarily associated with shortness of breath, cough and sputum production. Roflumilast, which is a long-acting selective inhibitor, reduces the anti-inflammatory effect of the main symptoms of COPD. The aim of this study was to compare the clinical effectiveness of adding roflumilast to the current treatment regimen of patients with severe COPD. Methods: To retrieve the marker studies, medical databases were searched up to February 2014. We included studies, which compared the clinical effectiveness and safety of roflumilast as concomitant to Long-acting ß2-agonist/Long-acting muscarinic antagonist (LABA/LAMA) regimen, in adult patients with severe COPD. The number of exacerbations, changes in the lung function FEV1, FEV1/FVC and quality of life were the major predefined outcomes. Meta-analysis of outcomes was performed by the RevMan software, with I2> 50%, representing considerable heterogeneity. Results: Seven randomized controlled trials and two systematic reviews were included. In terms of safety, participants were likely to experience more side effects from roflumilast compared to placebo, particularly gastrointestinal effects (diarrhea, nausea, vomiting), headache and weight loss. There was no significant difference in the risk of cardiac complications or flu-like symptoms or upper respiratory tract infection in the two groups. In terms of effectiveness, only a small improvement was observed in SGRQ (St George’s Respiratory Questionnaire) index. Roflumilast reduced moderate to severe attacks, and caused significant improvements in the lung function regardless of the severity of the disease and the concurrent use of other standard COPD therapies. Conclusion: Roflumilast anti-inflammatory therapy reduces the chronic bronchitis symptoms in patients with moderate to severe COPD, and it can be safely used with other drugs simultaneously. PMID:27390702

The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Jafari Andarian, Saeideh; Olyaeemanesh, Alireza; Hosseini, Seyed Alireza; Akbari Sari, Ali; Firoozbakhsh, Shahram; Nouhi Jadesi, Mojtaba; Mobinizadeh, Mohammadreza

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, which reduces the lung function and causes respiratory symptoms over time, and it is primarily associated with shortness of breath, cough and sputum production. Roflumilast, which is a long-acting selective inhibitor, reduces the anti-inflammatory effect of the main symptoms of COPD. The aim of this study was to compare the clinical effectiveness of adding roflumilast to the current treatment regimen of patients with severe COPD. To retrieve the marker studies, medical databases were searched up to February 2014. We included studies, which compared the clinical effectiveness and safety of roflumilast as concomitant to Long-acting ß2-agonist/Long-acting muscarinic antagonist (LABA/LAMA) regimen, in adult patients with severe COPD. The number of exacerbations, changes in the lung function FEV1, FEV1/FVC and quality of life were the major predefined outcomes. Meta-analysis of outcomes was performed by the RevMan software, with I(2)> 50%, representing considerable heterogeneity. Seven randomized controlled trials and two systematic reviews were included. In terms of safety, participants were likely to experience more side effects from roflumilast compared to placebo, particularly gastrointestinal effects (diarrhea, nausea, vomiting), headache and weight loss. There was no significant difference in the risk of cardiac complications or flu-like symptoms or upper respiratory tract infection in the two groups. In terms of effectiveness, only a small improvement was observed in SGRQ (St George's Respiratory Questionnaire) index. Roflumilast reduced moderate to severe attacks, and caused significant improvements in the lung function regardless of the severity of the disease and the concurrent use of other standard COPD therapies. Roflumilast anti-inflammatory therapy reduces the chronic bronchitis symptoms in patients with moderate to severe COPD, and it can be safely used with other drugs simultaneously.

Effect of metabolic syndrome and aging on Ca2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine.

PubMed

Badin, Jill K; Bruning, Rebecca S; Sturek, Michael

2018-05-03

Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca 2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca 2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca 2+ ([Ca 2+ ] i ) was assessed with fura-2 imaging. CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca 2+ ] i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca 2+ store release, increased Ca 2+ influx through voltage-gated Ca 2+ channels, and attenuated sarco-endoplasmic reticulum Ca 2+ ATPase activity. MetS old and MetS young swine had similar Ca 2+ dysregulation. Ca 2+ dysregulation, mainly the SR Ca 2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca 2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca 2+ handling dysfunction in CAD. Copyright © 2018 Elsevier Inc. All rights reserved.

Ethnoracial Differences in the Clinical Characteristics of Alzheimer Disease at Initial Presentation at an Urban Alzheimer’s Disease Center

PubMed Central

Livney, Melissa Gartenberg; Clark, Christopher M.; Karlawish, Jason H.; Cartmell, Su; Negrón, Mirna; Nuñez-Lopez, Jessica; Xie, Sharon X.; Entenza-Cabrera, Fernando; Vega, Irving E.; Arnold, Steven E.

2010-01-01

Objective To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Design Cross-sectional study. Participants A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic (“WNH”) subjects were recruited from primary care sites or by referral by primary care physicians. Measurements Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Results Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Conclusions Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported. PMID:21522051

Matrix metalloproteinase 10 is associated with disease severity and mortality in patients with peripheral arterial disease.

PubMed

Martinez-Aguilar, Esther; Gomez-Rodriguez, Violeta; Orbe, Josune; Rodriguez, Jose A; Fernández-Alonso, Leopoldo; Roncal, Carmen; Páramo, Jose A

2015-02-01

Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years. MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls. PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03). Our results suggest that MMP-10 is associated with severity and poor outcome in PAD. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Comparison of Xenon-Enhanced Area-Detector CT and Krypton Ventilation SPECT/CT for Assessment of Pulmonary Functional Loss and Disease Severity in Smokers.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Takenaka, Daisuke; Kaminaga, Shigeo; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2018-02-01

The objective of this study was to compare the capability of xenon-enhanced area-detector CT (ADCT) performed with a subtraction technique and coregistered 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity in smokers. Forty-six consecutive smokers (32 men and 14 women; mean age, 67.0 years) underwent prospective unenhanced and xenon-enhanced ADCT, 81m Kr-ventilation SPECT/CT, and pulmonary function tests. Disease severity was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. CT-based functional lung volume (FLV), the percentage of wall area to total airway area (WA%), and ventilated FLV on xenon-enhanced ADCT and SPECT/CT were calculated for each smoker. All indexes were correlated with percentage of forced expiratory volume in 1 second (%FEV 1 ) using step-wise regression analyses, and univariate and multivariate logistic regression analyses were performed. In addition, the diagnostic accuracy of the proposed model was compared with that of each radiologic index by means of McNemar analysis. Multivariate logistic regression showed that %FEV 1 was significantly affected (r = 0.77, r 2 = 0.59) by two factors: the first factor, ventilated FLV on xenon-enhanced ADCT (p < 0.0001); and the second factor, WA% (p = 0.004). Univariate logistic regression analyses indicated that all indexes significantly affected GOLD classification (p < 0.05). Multivariate logistic regression analyses revealed that ventilated FLV on xenon-enhanced ADCT and CT-based FLV significantly influenced GOLD classification (p < 0.0001). The diagnostic accuracy of the proposed model was significantly higher than that of ventilated FLV on SPECT/CT (p = 0.03) and WA% (p = 0.008). Xenon-enhanced ADCT is more effective than 81m Kr-ventilation SPECT/CT for the assessment of pulmonary functional loss and disease severity.

Sleep disorders and health-related quality of life in patients with interstitial lung disease.

PubMed

Mavroudi, Maria; Papakosta, Despoina; Kontakiotis, Theodore; Domvri, Kaliopi; Kalamaras, George; Zarogoulidou, Vasiliki; Zarogoulidis, Paul; Latka, Paschalina; Huang, Haidong; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos

2018-05-01

Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients' quality of life in relation to these disorders. Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire. Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group. In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.

IL-1β and IL-6 Upregulation in Children with H1N1 Influenza Virus Infection

PubMed Central

Chiaretti, Antonio; Pulitanò, Silvia; Barone, Giovanni; Ferrara, Pietro; Capozzi, Domenico; Riccardi, Riccardo

2013-01-01

The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1β and IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1β and IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1β and IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1β and IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients. PMID:23737648

Genetic risk profiling and gene signature modeling to predict risk of complications after IPAA.

PubMed

Sehgal, Rishabh; Berg, Arthur; Polinski, Joseph I; Hegarty, John P; Lin, Zhenwu; McKenna, Kevin J; Stewart, David B; Poritz, Lisa S; Koltun, Walter A

2012-03-01

Severe pouchitis and Crohn's disease-like complications are 2 adverse postoperative complications that confound the success of the IPAA in patients with ulcerative colitis. To date, approximately 83 single nucleotide polymorphisms within 55 genes have been associated with IBD. The aim of this study was to identify single-nucleotide polymorphisms that correlate with complications after IPAA that could be utilized in a gene signature fashion to predict postoperative complications and aid in preoperative surgical decision making. One hundred forty-two IPAA patients were retrospectively classified as "asymptomatic" (n = 104, defined as no Crohn's disease-like complications or severe pouchitis for at least 2 years after IPAA) and compared with a "severe pouchitis" group (n = 12, ≥ 4 episodes pouchitis per year for 2 years including the need for long-term therapy to maintain remission) and a "Crohn's disease-like" group (n = 26, presence of fistulae, pouch inlet stricture, proximal small-bowel disease, or pouch granulomata, occurring at least 6 months after surgery). Genotyping for 83 single-nucleotide polymorphisms previously associated with Crohn's disease and/or ulcerative colitis was performed on a customized Illumina genotyping platform. The top 2 single-nucleotide polymorphisms statistically identified as being independently associated with each of Crohn's disease-like and severe pouchitis were used in a multivariate logistic regression model. These single-nucleotide polymorphisms were then used to create probability equations to predict overall chance of a positive or negative outcome for that complication. The top 2 single-nucleotide polymorphisms for Crohn's disease-like complications were in the 10q21 locus and the gene for PTGER4 (p = 0.006 and 0.007), whereas for severe pouchitis it was NOD2 and TNFSF15 (p = 0.003 and 0.011). Probability equations suggested that the risk of these 2 complications greatly increased with increasing number of risk alleles, going as high as 92% for severe pouchitis and 65% for Crohn's disease-like complications. In this IPAA patient cohort, mutations in the 10q21 locus and the PTGER4 gene were associated with Crohn's disease-like complications, whereas mutations in NOD2 and TNFSF15 correlated with severe pouchitis. Preoperative genetic analysis and use of such gene signatures hold promise for improved preoperative surgical patient selection to minimize these IPAA complications.

Examining the Effects of Age on Health Outcomes of Chronic Obstructive Pulmonary Disease: Results From the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate Endpoints Cohorts.

PubMed

Parulekar, Amit D; Martinez, Carlos; Tsai, Chu-Lin; Locantore, Nicholas; Atik, Mustafa; Yohannes, Abebaw M; Kao, Christina C; Al-Azzawi, Hassan; Mohsin, Ali; Wise, Robert A; Foreman, Marilyn G; Demeo, Dawn L; Regan, Elizabeth A; Make, Barry J; Boriek, Aladin M; Wiener, Laura E; Hanania, Nicola A

2017-12-01

The prevalence of chronic obstructive pulmonary disease (COPD) and its associated comorbidities increase with age. However, little is understood about differences in the disease in patients over 65 years of age compared with younger patients. To determine disease characteristics of COPD and its impact in older patients compared with younger patients. We examined baseline characteristics of patients with COPD (global obstructive lung disease stage II-IV) in 2 large cohorts: Genetic Epidemiology of COPD Study (COPDGene) and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared demographics, indices of disease severity, prevalence of comorbidities, exacerbation frequency, and quality of life scores in patients ≥65 years of age vs patients <65 years of age. We also tested for associations of age with disease characteristics and health outcomes. In the COPDGene cohort, older patients (n = 1663) had more severe disease as measured by forced expiratory volume in 1 second (1.22 vs 1.52 L, P < .001), use of long-term oxygen therapy (35% vs 22%, P < .001), 6-minute walk distance (355 vs 375 m, P < .001), and radiographic evidence of emphysema (14% vs 8%, P < .001) and air trapping (47% vs 36%, P < .001) and were more likely to have comorbidities compared with younger patients (n = 2027). Similarly, in the ECLIPSE cohort, older patients (n = 1030) had lower forced expiratory volume in 1 second (1.22 vs 1.34 L, P < .001), greater use of long-term oxygen therapy (7% vs 5%, P = .02), shorter 6- minute walk distance (360 vs 389 m, P < .001), and more radiographic evidence of emphysema (17% vs 14%, P = .009) than younger patients (n = 1131). In adjusted analyses of both cohorts, older age was associated with decreased frequency of exacerbations [odds ratio = 0.52, 95% confidence interval (CI) = 0.43-0.64 in COPDGene, odds ratio = 0.79, 95% CI = 0.64-0.99 in ECLIPSE] and a better quality of life (lower St. Georges respiratory questionnaire score) (β = -8.7, 95% CI = -10.0 to -7.4 in COPDGene, β = -4.4, 95% CI = -6.1 to -3.2 in ECLIPSE). Despite greater severity of illness, older patients with COPD had better quality of life and reported fewer exacerbations than younger patients. Although this observation needs to be explored further, it may be related to the fact that older patients change their expectations and learn to adapt to their disease. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.

PubMed

An, Hongyan; Lim, Chai; Guillemin, Gilles J; Vollmer-Conna, Ute; Rawlinson, William; Bryant, Katherine; Tedla, Nicodemus

2016-01-01

Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.

The association of sociodemographic and objectively-assessed disease variables with fatigue in systemic sclerosis: an analysis of 785 Canadian Scleroderma Research Group Registry patients.

PubMed

Levis, Brooke; Kwakkenbos, Linda; Hudson, Marie; Baron, Murray; Thombs, Brett D

2017-02-01

Fatigue is prevalent among patients with systemic sclerosis (SSc). To date, studies investigating fatigue in SSc have been hampered by the instruments used to measure fatigue in SSc and have included patient-reported rather than objectively-rated measures of disease. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale is a validated measure for assessing fatigue in SSc that, compared to other instruments, provides good coverage of the full range of the fatigue spectrum. The objective of this study was to assess sociodemographic and objectively-rated disease-related associates of fatigue, as measured by the FACIT-F, in a large sample of patients with SSc. Fatigue was assessed using the FACIT-F scale. Disease severity was assessed using Medsger's severity scale. Multivariable linear regression was performed to assess the independent associations between sociodemographic and medical variables and fatigue. Among 785 patients, the mean FACIT-F score was 32.2 (SD = 12.1). Being age 40-49 (reference = 60+; standardized regression coefficient (β) = -0.11), less than post-secondary education (β = 0.07), having more medical comorbidities (β = -0.11) and more severe muscle (β = -0.10), gastrointestinal (β = -0.15), lung (β = -0.13), and general system disease severity (β = -0.13) were independently associated with more fatigue (p < 0.05). Fatigue in SSc was independently associated with more severe disease. These data contribute to a better understanding of fatigue in SSc and help inform patient-centered research in SSc.

Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease

PubMed Central

Üçeyler, Nurcan; Homola, György A.; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

2014-01-01

A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity. PMID:24475221

Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan.

PubMed

Ku, Li-Jung Elizabeth; Pai, Ming-Chyi; Shih, Pei-Yu

2016-01-01

Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures. This study included 231 dementia patient-caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses. Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients. Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan.

Disease burden attributed to alcohol: How methodological advances in the Global Burden of Disease 2013 study have changed the estimates in Sweden.

PubMed

Kellerborg, Klas; Danielsson, Anna-Karin; Allebeck, Peter; Coates, Matthew M; Agardh, Emilie

2016-08-01

The Global Burden of Disease (GBD) study continuously refines its estimates as new data and methods become available. In the latest iteration of the study, GBD 2013, changes were made related to the disease burden attributed to alcohol. The aim of this study was to briefly present these changes and to compare the disease burden attributed to alcohol in Swedish men and women in 2010 using previous and updated methods. In the GBD study, the contribution of alcohol to the burden of disease is estimated by theoretically assessing how much of the disease burden can be avoided by reducing the consumption of alcohol to zero. The updated methods mainly consider improved measurements of alcohol consumption, including less severe alcohol dependence, assigning the most severe injuries and removing the protective effect of drinking on cardiovascular diseases if combined with binge drinking. The overall disease burden attributed to alcohol in 2010 increased by 14% when using the updated methods. Women accounted for this overall increase, mainly because the updated methods led to an overall higher alcohol consumption in women. By contrast, the overall burden decreased in men, one reason being the lower overall alcohol consumption with the new methods. In men, the inclusion of less severe alcohol dependence resulted in a large decrease in the alcohol attributed disease burden. This was, however, evened out to a great extent by the increase in cardiovascular disease and injuries. CONCLUSIONS WHEN USING THE UPDATED GBD METHODS, THE OVERALL DISEASE BURDEN ATTRIBUTED TO ALCOHOL INCREASED IN WOMEN, BUT NOT IN MEN. © 2016 the Nordic Societies of Public Health.

Comorbidity of Narcolepsy Type 1 With Autoimmune Diseases and Other Immunopathological Disorders: A Case-Control Study

PubMed Central

Martinez-Orozco, Francisco Javier; Vicario, Jose Luis; De Andres, Clara; Fernandez-Arquero, Miguel; Peraita-Adrados, Rosa

2016-01-01

Background Several evidences suggest that autoimmune diseases (ADs) tend to co-occur in an individual and within the same family. Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a selective loss of hypocretin-producing neurons due to a mechanism of neural destruction that indicates an autoimmune pathogenesis, although no evidence is available. We report on the comorbidity of ADs and other immunopathological diseases (including allergy diseases) in narcolepsy. Methods We studied 158 Caucasian NT1 patients (60.7% male; mean age 49.4 ± 19.7 years), in whom the diagnosis was confirmed by polysomnography followed by a multiple sleep latency test, or by hypocretin-1 levels measurements. Results Thirty out of 158 patients (18.99%; 53.3% female; 29 sporadic and one familial cases) had one or more immunopathological diseases associated. A control group of 151 subjects were matched by gender and age with the narcolepsy patients. Results demonstrated that there was a higher frequency of ADs in our series of narcolepsy patients compared to the sample of general population (odds ratio: 3.17; 95% confidence interval: 1.01 - 10.07; P = 0.040). A temporal relationship with the age at onset of the diseases was found. Conclusions Cataplexy was significantly more severe in NT1 patients with immunopathological diseases, and immunopathological diseases are a risk factor for severe forms of cataplexy in our series (odds ratio: 23.6; 95% confidence interval: 5.5 - 100.1). PMID:27298657

Evaluation of strategies for the eradication of Pseudorabies virus (Aujeszky's disease) in commercial swine farms in Chiang-Mai and Lampoon Provinces, Thailand, using a simulation disease spread model.

PubMed

Ketusing, N; Reeves, A; Portacci, K; Yano, T; Olea-Popelka, F; Keefe, T; Salman, M

2014-04-01

Several strategies for eradicating Pseudorabies virus (Aujeszky's disease) in Chiang-Mai and Lampoon Provinces, Thailand, were compared using a computer simulation model, the North American Animal Disease Spread Model (NAADSM). The duration of the outbreak, the number of affected herds and the number of destroyed herds were compared during these simulated outbreaks. Depopulation, zoning for restricted movement and improved detection and vaccination strategies were assessed. The most effective strategies to eradicate Pseudorabies as per the findings from this study are applying depopulation strategies with MOVEMENT RESTRICTIONS in 3-, 8- and 16-km ZONES surrounding infected herds and enhancing the eradication with vaccination campaign on 16-km radius surrounding infected herds. © 2012 Blackwell Verlag GmbH.

Spectral separability and mapping potential of cassava leaf damage symptoms caused by whiteflies (Bemisia tabaci).

PubMed

Sims, Neil C; De Barro, Paul; Newnham, Glenn J; Kalyebi, Andrew; Macfadyen, Sarina; Malthus, Tim J

2018-01-01

This study examines whether leaf spectra can be used to measure damage to cassava plants from whitefly (Bemisia tabaci), and the potential to translate measurements from leaf to landscape scale in eastern Africa. Symptoms of the cassava brown streak disease (CBSD) and cassava mosaic disease (CMD) viruses, and sooty mould (SM) blackening of lower leaves from whiteflies feeding on the upper leaves, were measured at the leaf scale with a high-resolution spectroradiometer and a single photon avalanche diode (SPAD) meter, which retrieves relative chlorophyll concentration. Spectral measurements were compared to the five-level visual scores used to assess the severity of each of the three damaging agents in the field, and also to leaf chemistry data. Leaves exhibiting severe CBSD and CMD were spectrally indistinguishable from leaves without any symptoms. Severe SM was spectrally distinctive but is likely to be difficult to map because of its occurrence in the lower crown. SPAD measurements were highly correlated with most foliar chemistry measurements and field scores of disease severity. Regression models between simulated Sentinel 2 bands, field scores and SPAD measurements were strongest using wavelengths with high importance weightings in random forest models. SPAD measurements are highly correlated to many foliar chemistry parameters, and should be considered for use in mapping disease severity over larger areas. Remaining challenges for mapping relate to the subtle expression of symptoms, the spatial distribution of disease severity within fields, and the small size and complex structure of the cassava fields themselves. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Spectral separability and mapping potential of cassava leaf damage symptoms caused by whiteflies (Bemisia tabaci)

PubMed Central

De Barro, Paul; Newnham, Glenn J; Kalyebi, Andrew; Macfadyen, Sarina; Malthus, Tim J

2017-01-01

Abstract BACKGROUND This study examines whether leaf spectra can be used to measure damage to cassava plants from whitefly (Bemisia tabaci), and the potential to translate measurements from leaf to landscape scale in eastern Africa. Symptoms of the cassava brown streak disease (CBSD) and cassava mosaic disease (CMD) viruses, and sooty mould (SM) blackening of lower leaves from whiteflies feeding on the upper leaves, were measured at the leaf scale with a high‐resolution spectroradiometer and a single photon avalanche diode (SPAD) meter, which retrieves relative chlorophyll concentration. Spectral measurements were compared to the five‐level visual scores used to assess the severity of each of the three damaging agents in the field, and also to leaf chemistry data. RESULTS Leaves exhibiting severe CBSD and CMD were spectrally indistinguishable from leaves without any symptoms. Severe SM was spectrally distinctive but is likely to be difficult to map because of its occurrence in the lower crown. SPAD measurements were highly correlated with most foliar chemistry measurements and field scores of disease severity. Regression models between simulated Sentinel 2 bands, field scores and SPAD measurements were strongest using wavelengths with high importance weightings in random forest models. CONCLUSION SPAD measurements are highly correlated to many foliar chemistry parameters, and should be considered for use in mapping disease severity over larger areas. Remaining challenges for mapping relate to the subtle expression of symptoms, the spatial distribution of disease severity within fields, and the small size and complex structure of the cassava fields themselves. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:28851022

Comparison of the use of scapular ultrasonography, physical examination, and measurement of serum biomarkers of bone turnover versus scintigraphy for detection of bone fragility syndrome in horses.

PubMed

Arens, Amanda M; Puchalski, Sarah M; Whitcomb, Mary Beth; Bell, Robin; Gardner, Ian A; Stover, Susan M

2013-01-01

To define scintigraphic, physical examination, and scapular ultrasonographic findings consistent with bone fragility syndrome (BFS) in horses; develop indices of BFS severity; and assess accuracy of physical examination, scapular ultrasonography, and serum biomarkers for BFS diagnosis. Prospective case-control study. 48 horses (20 horses with BFS and 28 control horses). Horses underwent forelimb scintigraphic evaluation, physical examination, scapular ultrasonography, and serum collection. Scintigraphy was used as a reference standard to which physical examination, scapular ultrasonography, and concentrations of serum biomarkers (carboxy-terminal telopeptide of collagen crosslinks and bone-specific alkaline phosphatase activity) were compared for assessing accuracy in BFS diagnosis. A diagnosis of BFS was strongly supported on scintigraphy by ≥ 2 regions of increased radiopharmaceutical uptake, including 1 region in the scapular spine and 1 region in the scapular body or ribs; on physical examination by lateral bowing of the scapulae; and on ultrasonography by widening of the scapular spine. None of the tests evaluated were accurate enough to replace scintigraphy for mild disease; however, physical examination and scapular ultrasonography were accurate in horses with moderate to severe BFS. Serum biomarkers were not accurate for BFS diagnosis. Scintigraphy remained the most informative diagnostic modality for BFS, providing insight into disease severity and distribution; however, physical examination and scapular ultrasonographic abnormalities were diagnostic in horses with moderate to severe disease. Proposed severity indices classified the spectrum of disease manifestations. Clearly defined criteria for interpretation of diagnostic tests aid in the detection of BFS. Severity indices may be useful for assessing disease progression and response to treatment.

Markers of activated inflammatory cells correlate with severity of liver damage in children with nonalcoholic fatty liver disease.

PubMed

De Vito, Rita; Alisi, Anna; Masotti, Andrea; Ceccarelli, Sara; Panera, Nadia; Citti, Arianna; Salata, Michele; Valenti, Luca; Feldstein, Ariel E; Nobili, Valerio

2012-07-01

Concomitantly to the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in children. NAFLD encompasses a spectrum of histological damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), with possible progression to cirrhosis. There is growing evidence that the immune system plays a pivotal role in the initiation and progression to NASH but the cellular nature of the hepatic inflammation is still unknown. The present study includes 34 children with biopsy-proven NAFLD. Liver damage was evaluated by the NAFLD activity score (NAS), and the inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3 and CD163 which are markers of leukocytes, T cells and activated Kupffer cells/macrophages, respectively. Our results have shown that CD45+ (P<0.0001) and CD163+ (P<0.0001) cells were markedly increased in children with severe histological activity (NAS≥5) compared to children with lower activity (NAS<5), whereas CD3+ cells were significantly lower (P<0.01) in children with severe histological activity. There was a significant association between the numbers of CD45+, CD3+ and CD163+ cells, regarding both the portal tract and liver lobule, and the severity of steatosis, ballooning and fibrosis (P<0.01). These data suggest that the severity and composition of the inflammatory infiltrate correlate with steatosis and the severity of disease in children with NAFLD. Moreover, a decrease in CD3+ cells may be involved in the pathogenesis of liver damage. Future studies should evaluate whether it can predict the progression of liver disease independently of established histological scores.

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

PubMed

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-12-01

Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients.

PubMed

Nevo, S; Swan, V; Enger, C; Wojno, K J; Bitton, R; Shabooti, M; Fuller, A K; Jones, R J; Braine, H G; Vogelsang, G B

1998-02-15

Acute bleeding after bone marrow transplantation (BMT) was investigated in 1,402 patients receiving transplants at Johns Hopkins Hospital between January 1, 1986 and June 30, 1995. Bleeding categorization was based on daily scores of intensity used by the blood transfusion service. Moderate and severe episodes were analyzed for bleeding sites. Analysis of the cause of death and the interval of the bleeding episode to outcome endpoints was recorded. Survival estimates were computed for 1,353 BMT patients. The overall incidence was 34%. Minor bleeding was seen in 10.6%, moderate bleeding was seen in 11.3%, and severe bleeding was seen in 12% of all patients. Fourteen percent of patients had moderate or severe gastrointestinal hemorrhage, 6.4% had moderate or severe hemorrhagic cystitis, 2.8% had pulmonary hemorrhage, and 2% had intracranial hemorrhage. Sixty-one percent had 1 bleeding site and 34.4% had more than 1 site. Moderate and severe bleeding was more prevalent in allogeneic (31%) and unrelated patients (62.5%) compared with autologous patients (18.5%). Significant distribution of incidence was found among the different diagnoses, but not by disease status in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma. Bleeding was associated with significantly reduced survival in allogeneic, autologous, and unrelated BMT and in each disease category except multiple myeloma. Survival was correlated with the bleeding intensity, bleeding site, and the number of sites. Although close temporal association was evident to mortality, bleeding was recorded as the cause of death in only the minority of cases compared with other toxicities after BMT (graft-versus-host disease, infections, and preparative regimen toxicity). Acute bleeding is a common complication after BMT that is profoundly associated with morbidity and mortality. Although bleeding was not a direct cause of death in the majority of cases, it has a potential prognostic implication as a predictor of poor outcome in clinical assessment of patients after BMT.

Type D personality is related to severity of acute coronary syndrome in patients with recurrent cardiovascular disease.

PubMed

Garcia-Retamero, Rocio; Petrova, Dafina; Arrebola-Moreno, Antonio; Catena, Andrés; Ramírez-Hernández, José A

2016-09-01

To investigate the relationship between Type D (distressed) personality and cardiac biomarkers of disease severity in patients with acute coronary syndrome. To identify potential mechanisms behind the effect of Type D personality on cardiovascular disease (CVD). Cross-sectional. Patients (N = 215) with acute coronary syndrome completed a survey including a measure of Type D personality. Blood samples including a lipid profile and cardiac enzymes were taken within 3 days after the cardiovascular event. Data were analysed using simple correlations, multiple regressions, and mediation analyses. Type D personality was more predictive of severity of the acute coronary syndrome among patients with previous CVD compared to patients without previous CVD. Among patients with previous CVD, Type D personality was associated with the presence of ST elevation (R(2)  =.07) and more damage to the myocardium as indicated by higher troponin-I (R(2)  = .05) and myoglobin (R(2)  = .07) levels. These effects were independent from demographics, CV risk factors, and depression. Lower HDL cholesterol levels mediated the relationship between Type D personality and disease severity (Κ(2)  = .12 [95% CI 0.02, 0.28]) for myoglobin and Κ(2)  = .08 [95% CI 0.01, 0.21] for troponin-I). Type D personality was related to a worse lipid profile and more severe acute coronary syndrome in patients with previous history of CVD. Given the strong relationship between disease severity and subsequent mortality, these results suggest that severity of the myocardial infarction may be a potential mechanism explaining increased mortality in Type D patients with recurrent CVD. Statement of contribution What is already known on this subject? Type D personality has been related to worse outcomes in cardiac patients. However, recent studies show mixed results, suggesting the need to clarify potential mechanisms. What does this study add? Type D personality is related to severity of acute coronary syndrome in patients with previous history of cardiovascular disease. This effect is partially accounted for by lower HDL levels in Type D patients. Disease severity is a potential mechanism by which Type D personality may affect cardiovascular health of patients with recurrent CVD. © 2016 The British Psychological Society.

Effectiveness of Home-based Management of Newborn Infections by Community Health Workers in Rural Bangladesh

PubMed Central

Baqui, Abdullah H.; Arifeen, Shams E.; Williams, Emma K.; Ahmed, Saifuddin; Mannan, Ishtiaq; Rahman, Syed M.; Begum, Nazma; Seraji, Habibur R.; Winch, Peter J.; Santosham, Mathuram; Black, Robert E.; Darmstadt, Gary L.

2010-01-01

Background Infections account for about half of neonatal deaths in low-resource settings. Limited evidence supports home-based treatment of newborn infections by community health workers (CHW). Methods In one study arm of a cluster randomized controlled trial, CHWs assessed neonates at home using a 20-sign clinical algorithm and classified sick neonates as having very severe disease or possible very severe disease. Over a two-year period, 10 585 live births were recorded in the study area. CHWs assessed 8474 (80%) of the neonates within the first week of life and referred neonates with signs of severe disease. If referral failed but parents consented to home treatment, CHWs treated neonates with very severe disease or possible very severe disease with multiple signs, using injectable antibiotics. Results For very severe disease, referral compliance was 34% (162/478 cases), and home treatment acceptance was 43% (204/478 cases). The case fatality rate was 4.4% (9/204) for CHW treatment, 14.2% (23/162) for treatment by qualified medical providers, and 28.5% (32/112) for those who received no treatment or who were treated by other unqualified providers. After controlling for differences in background characteristics and illness signs among treatment groups, newborns treated by CHWs had a hazard ratio of 0.22 (95% confidence interval 0.07–0.71) for death during the neonatal period and those treated by qualified providers had a hazard ratio of 0.61 (95% confidence interval of 0.37–0.99), compared with newborns who received no treatment or were treated by untrained providers. Significantly increased hazards ratios of death were observed for neonates with convulsions (HR 6.54; 95% CI 3.98–10.76), chest in-drawing (HR 2.38, 95% CI 1.29–4.39), temperature < 35.3°C (HR 3.47, 95% CI 1.30–9.24), unconsciousness (HR 7.92, 95% CI 3.13–20.04). Conclusions Home treatment of very severe disease in neonates by CHWs was effective and acceptable in a low-resource setting in Bangladesh. PMID:19289979

Premorbid personality in chronic fatigue syndrome as determined by the Temperament and Character Inventory.

PubMed

Fukuda, Sanae; Kuratsune, Hirohiko; Tajima, Seiki; Takashima, Shoko; Yamagutchi, Kouzi; Nishizawa, Yoshiki; Watanabe, Yasuyoshi

2010-01-01

Using the Temperament and Character Inventory (TCI), we examined personality characteristics in patients with chronic fatigue syndrome (CFS) compared with healthy control subjects, and CFS patients with and without psychiatric diseases. There have been no previous reports assessing personality in CFS patients using the TCI. A total of 211 CFS patients and 90 control subjects completed the TCI and the Chalder Fatigue Scale questionnaires. Compared with control subjects, CFS patients demonstrated significantly lower premorbid Novelty Seeking, and higher Harm Avoidance and persistence. The fatigue score for CFS patients with psychiatric diseases was higher than that for CFS patients without psychiatric diseases. Patients with CFS with psychiatric diseases showed lower premorbid Self-Directedness when compared with CFS patients without psychiatric diseases. The fatigue score was negatively correlated with premorbid Self-Directedness and Cooperativeness, and positively correlated with Harm Avoidance among CFS patients. This study supported the stereotyped image of CFS patients as perfectionists, which is similar to the Persistence score, and neurotics, which is similar to the Harm Avoidance score. Patients displaying greater neuroticisms and poorer social and communication skills, similar to the Self-Directedness and Cooperativeness scores, tend to have intercurrent psychiatry diseases and show more severe symptoms of CFS.

Increased polyamines as protective disease modifiers in congenital muscular dystrophy.

PubMed

Kemaladewi, D U; Benjamin, J S; Hyatt, E; Ivakine, E A; Cohn, R D

2018-06-01

Most Mendelian disorders, including neuromuscular disorders, display extensive clinical heterogeneity that cannot be solely explained by primary genetic mutations. This phenotypic variability is largely attributed to the presence of disease modifiers, which can exacerbate or lessen the severity and progression of the disease. LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD) is a fatal degenerative muscle disease resulting from mutations in the LAMA2 gene encoding Laminin-α2. Progressive muscle weakness is predominantly observed in the lower limbs in LAMA2-CMD patients, whereas upper limbs muscles are significantly less affected. However, very little is known about the molecular mechanism underlying differential pathophysiology between specific muscle groups. Here, we demonstrate that the triceps muscles of the dy2j/dy2j mouse model of LAMA2-CMD demonstrate very mild myopathic findings compared with the tibialis anterior (TA) muscles that undergo severe atrophy and fibrosis, suggesting a protective mechanism in the upper limbs of these mice. Comparative gene expression analysis reveals that S-Adenosylmethionine decarboxylase (Amd1) and Spermine oxidase (Smox), two components of polyamine pathway metabolism, are downregulated in the TA but not in the triceps of dy2j/dy2j mice. As a consequence, the level of polyamine metabolites is significantly lower in the TA than triceps. Normalization of either Amd1 or Smox expression in dy2j/dy2j TA ameliorates muscle fibrosis, reduces overactive profibrotic TGF-β pathway and leads to improved locomotion. In summary, we demonstrate that a deregulated polyamine metabolism is a characteristic feature of severely affected lower limb muscles in LAMA2-CMD. Targeted modulation of this pathway represents a novel therapeutic avenue for this devastating disease.

Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease.

PubMed

Luckschander, Nicole; Allenspach, Karin; Hall, Jean; Seibold, Frank; Gröne, Andrea; Doherr, Marcus G; Gaschen, Frédéric

2006-01-01

The goal of this study was to investigate the correlation between perinuclear antineutrophilic cytoplasmic antibody (pANCA) and clinical scores before and after treatment in diarrheic dogs with food-responsive disease (FRD) or inflammatory bowel disease (IBD). pANCA serology was evaluated prospectively by indirect immunofluorescence in 65 dogs with signs of gastrointestinal disease, and if positive, pANCA antibody titers were determined. Thirty-nine dogs with FRD responded to a novel diet, and 26 dogs with IBD were treated with corticosteroids. The severity of clinical signs was scored by means of a canine IBD activity index (CIBDAI). At initial examination, a significantly (P = .002) higher percentage of dogs were pANCA-positive in the FRD group (62%) compared with the IBD group (23%). pANCA titers were significantly higher (P = .003) before treatment in the FRD group (median titer 100) compared with the IBD group (median titer 1). However, there was no difference in pANCA titers between the groups after respective treatments because dogs in the IBD group had a significant increase in pANCA titer after treatment. The CIBDAI score decreased significantly (P < .001) after treatment in both groups (74% moderate to severe in FRD dogs before versus 8% after treatment; 85% moderate to severe in IBD dogs before versus 32% after treatment). There was no correlation between pANCA status in FRD or IBD dogs before treatment and scores for CIBDAI, endoscopy, or histopathology before or after treatment, except for the endoscopic duodenal score in dogs with FRD after treatment (P = .03). A positive pANCA test before therapy may aid in the diagnosis of FRD.

Relationship of Hypertension to Coronary Atherosclerosis and Cardiac Events in Patients With Coronary Computed Tomographic Angiography.

PubMed

Nakanishi, Rine; Baskaran, Lohendran; Gransar, Heidi; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Cury, Ricardo; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Kaufmann, Philipp A; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Pontone, Gianluca; Andreini, Daniele; Rubinshtein, Ronen; Bax, Jeroen; Jones, Erica; Hindoyan, Niree; Gomez, Millie; Lin, Fay Y; Min, James K; Berman, Daniel S

2017-08-01

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events. © 2017 American Heart Association, Inc.

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

PubMed

Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

2017-08-01

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Exome sequencing identifies SUCO mutations in mesial temporal lobe epilepsy.

PubMed

Sha, Zhiqiang; Sha, Longze; Li, Wenting; Dou, Wanchen; Shen, Yan; Wu, Liwen; Xu, Qi

2015-03-30

Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CRISPR/Cas9-mediated correction of human genetic disease.

PubMed

Men, Ke; Duan, Xingmei; He, Zhiyao; Yang, Yang; Yao, Shaohua; Wei, Yuquan

2017-05-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system (CRISPR/Cas9) provides a powerful tool for targeted genetic editing. Directed by programmable sequence-specific RNAs, this system introduces cleavage and double-stranded breaks at target sites precisely. Compared to previously developed targeted nucleases, the CRISPR/Cas9 system demonstrates several promising advantages, including simplicity, high specificity, and efficiency. Several broad genome-editing studies with the CRISPR/Cas9 system in different species in vivo and ex vivo have indicated its strong potential, raising hopes for therapeutic genome editing in clinical settings. Taking advantage of non-homologous end-joining (NHEJ) and homology directed repair (HDR)-mediated DNA repair, several studies have recently reported the use of CRISPR/Cas9 to successfully correct disease-causing alleles ranging from single base mutations to large insertions. In this review, we summarize and discuss recent preclinical studies involving the CRISPR/Cas9-mediated correction of human genetic diseases.

Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology.

PubMed

Hamilton, Roy; Patel, Sunil; Lee, Edward B; Jackson, Eric M; Lopinto, Joanna; Arnold, Steven E; Clark, Christopher M; Basil, Anuj; Shaw, Leslie M; Xie, Sharon X; Grady, M Sean; Trojanowski, John Q

2010-10-01

To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology.

Efficacy of Various Scoring Systems for Predicting the 28-Day Survival Rate among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease Requiring Emergency Intensive Care.

PubMed

Feng, Zhihong; Wang, Tao; Liu, Ping; Chen, Sipeng; Xiao, Han; Xia, Ning; Luo, Zhiming; Wei, Bing; Nie, Xiuhong

2017-01-01

We aimed to investigate the efficacy of four severity-of-disease scoring systems in predicting the 28-day survival rate among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring emergency care. Clinical data of patients with AECOPD who required emergency care were recorded over 2 years. APACHE II, SAPS II, SOFA, and MEDS scores were calculated from severity-of-disease indicators recorded at admission and compared between patients who died within 28 days of admission (death group; 46 patients) and those who did not (survival group; 336 patients). Compared to the survival group, the death group had a significantly higher GCS score, frequency of comorbidities including hypertension and heart failure, and age ( P < 0.05 for all). With all four systems, scores of age, gender, renal inadequacy, hypertension, coronary heart disease, heart failure, arrhythmia, anemia, fracture leading to bedridden status, tumor, and the GCS were significantly higher in the death group than the survival group. The prediction efficacy of the APACHE II and SAPS II scores was 88.4%. The survival rates did not differ significantly between APACHE II and SAPS II ( P = 1.519). Our results may guide triage for early identification of critically ill patients with AECOPD in the emergency department.

Dispositional optimism, depression, disability and quality of life in Parkinson’s disease

PubMed Central

Gison, Annalisa; Dall’Armi, Valentina; Donati, Valentina; Rizza, Federica; Giaquinto, Salvatore

2014-01-01

Summary Very little research on dispositional optimism (DO) has been carried out in the field of Parkinson’s disease (PD). The present cross-sectional study, focusing on this personality trait, was performed with two main aims: i) to compare DO between patients with PD and a control group (CG); ii) to perform, in the PD group, a regression analysis including health-related variables, such as depression, anxiety, quality of life (QoL) and activities of daily living. Seventy PD participants and 70 healthy volunteers were enrolled in the study. The Mann-Whitney test was used to compare life orientation between the PD and CG groups. In the PD group, Pearson’s correlation analysis was used to investigate the relationship between the measures of DO and the other variables. Means of log-linear regression were also used. Mean ratios adjusted for sex, age, education, and severity of disease were estimated, with relative 95% confidence intervals and p-values. The main results were as follows: i) no significant difference in DO was found between the PD participants and the CG; ii) DO was positively associated with QoL and emotional distress and inversely correlated with the Unified Parkinson’s Disease Rating Scale; iii) DO was not correlated with disability. In conclusion, high DO predicts a satisfactory quality of life, low emotional distress and reduced disease severity in PD. PMID:25306121

Morphometric assessment of periodontal tissues in relation to periodontal disease in dogs.

PubMed

Kyllar, Michal; Doskarova, Barbora; Paral, Vaclav

2013-01-01

Dimensions of periodontal tissues are thought to predispose to the development of periodontal disease in man and dogs. Several studies have suggested that thin gingiva correlates with an increased incidence of periodontal disease. In this study, we hypothesized that the dimensions of periodontal tissues will vary in different breeds of dogs and could possibly correlate with the incidence of periodontal disease. Forty-two jaws of dogs aged up to 5-years were examined post-mortem and gingival and alveolar bone thickness were measured using methods of transgingival probing and digital calipers, respectively. Dogs were divided into three groups based on their body weight. Group I (< 5.0 kg; n=21), group II (5 to 10 kg; n=11), and group III (10 to 15 kg; n=10). Thickness of gingiva ranged from 0.30-mm to 3.2-mm and was relatively thinner in group I than in group II and III based on the means of ratios comparison. Alveolar bone thickness ranged from 0.27-mm to 4.1-mm and was relatively thinner in group I compared with groups II and III. Our study showed significantly thinner gingiva and alveolar bone in toy breed dogs compared with small and medium-sized breed dogs. Both gingival and alveolar bone dimensions may be predictors for severity of periodontal disease and influence clinical outcome in certain periodontal surgical procedures.

Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study.

PubMed

Kurth, Florian; Develoux, Michel; Mechain, Matthieu; Clerinx, Jan; Antinori, Spinello; Gjørup, Ida E; Gascon, Joaquím; Mørch, Kristine; Nicastri, Emanuele; Ramharter, Michael; Bartoloni, Alessandro; Visser, Leo; Rolling, Thierry; Zanger, Philipp; Calleri, Guido; Salas-Coronas, Joaquín; Nielsen, Henrik; Just-Nübling, Gudrun; Neumayr, Andreas; Hachfeld, Anna; Schmid, Matthias L; Antonini, Pietro; Pongratz, Peter; Kern, Peter; Saraiva da Cunha, José; Soriano-Arandes, Antoni; Schunk, Mirjam; Suttorp, Norbert; Hatz, Christoph; Zoller, Thomas

2015-11-01

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Static and Functional Balance in Individuals With COPD: Comparison With Healthy Controls and Differences According to Sex and Disease Severity.

PubMed

de Castro, Larissa A; Ribeiro, Laís Rg; Mesquita, Rafael; de Carvalho, Débora R; Felcar, Josiane M; Merli, Myriam F; Fernandes, Karen Bp; da Silva, Rubens A; Teixeira, Denilson C; Spruit, Martijn A; Pitta, Fabio; Probst, Vanessa S

2016-11-01

Studies have shown that individuals with COPD have impaired body balance, probably caused by the disease's multisystemic manifestations plus age-related decline in balance, potentially increasing the risk of falling and its consequences. However, little is known about the profile of individuals with COPD who present balance impairments, especially related to sex and disease severity stages. The aim of this work was to compare static and functional balance between subjects with COPD and healthy controls and to check possible differences according to sex and degrees of disease severity. Forty-seven subjects with COPD and 25 healthy controls were included in this study. Their static balance was assessed in one-legged stance using a force platform and functional balance with the Timed Up and Go test. Additionally, participants performed spirometry, the 6-min walk test and isometric quadriceps maximal voluntary contraction assessment. Disease severity was classified according to the Global Initiative for Obstructive Lung Disease stages and BODE (body mass index, air-flow obstruction, dyspnea, and exercise capacity) scores. In comparison with healthy controls, subjects with COPD had worse static (center of pressure displacement area: 9.3 ± 1.9 cm 2 vs 11.6 ± 4.0 cm 2 , respectively, P = .01) and functional balance (Timed Up and Go test: 8.5 ± 1.3 s vs 10.3 ± 1.8 s, respectively, P < .001). In the COPD group, men performed better in the Timed Up and Go test than women (9.8 ± 1.2 s vs 10.9 ± 2.2 s, respectively, P = .03), whereas women presented a better static balance in comparison with men for all parameters related to center of pressure (P < .005 for all). Disease severity did not affect any balance results. Individuals with COPD had worse static and functional balance in comparison with healthy controls. Sex can mediate these results, depending on the type of balance evaluation (force platform or functional test). Balance performance was similar among the groups classified according to disease severity. Copyright © 2016 by Daedalus Enterprises.

Computing the variations in the self-similar properties of the various gait intervals in Parkinson disease patients.

PubMed

Manjeri Keloth, Sana; Arjunan, Sridhar P; Kumar, Dinesh

2017-07-01

This study has investigated the stride, swing, stance and double support intervals of gait for Parkinson's disease (PD) patients with different levels of severity. Self-similar properties of the gait signal were analyzed to investigate the changes in the gait pattern of the healthy and PD patients. To understand the self-similar property, detrended fluctuation analysis was performed. The analysis shows that the PD patients have less defined gait when compared to healthy. The study also shows that among the stance and swing phase of stride interval, the self-similarity is less for swing interval when compared to the stance interval of gait and decreases with the severity of gait. Also, PD patients show decreased self-similar patterns in double support interval of gait. This suggest that there are less rhythmic gait intervals and a sense of urgency to remain in support phase of gait by the PD patients.

Evaluating Hospital-Based Surveillance for Outbreak Detection in Bangladesh: Analysis of Healthcare Utilization Data

PubMed Central

Nikolay, Birgit; Salje, Henrik; Sturm-Ramirez, Katharine; Azziz-Baumgartner, Eduardo; Homaira, Nusrat; Iuliano, A. Danielle; Paul, Repon C.; Hossain, M. Jahangir; Cauchemez, Simon; Gurley, Emily S.

2017-01-01

Background The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country’s ability to meet these requirements. Methods and Findings We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged <5 y or from the lowest socioeconomic group and fatal respiratory disease cases aged ≥60 y were underrepresented. Our estimates of outbreak detection rely on suspected cases that attend a surveillance hospital receiving laboratory confirmation of disease and being reported to the surveillance system. The extent to which this occurs will depend on disease characteristics (e.g., severity and symptom specificity) and surveillance resources. Conclusion We present a new approach to evaluating the sensitivity and representativeness of hospital-based surveillance, making it possible to predict its ability to detect emerging threats. PMID:28095468

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

Soluble CD40 ligand in prediction of acute severe pancreatitis

PubMed Central

Frossard, Jean Louis; Morel, Philippe; Kwak, Brenda; Pastor, Catherine; Berney, Thierry; Buhler, Léo; Von Laufen, Alain; Demulder, Sandrine; Mach, Francois

2006-01-01

AIM: To assess the early predictability of the soluble CD40L (sCD40L) in pancreatitis severity. METHODS: Between February 2000 and February 2003, 279 consecutive patients with acute pancreatitis were prospectively enrolled in our study. In this report, 40 patients with mild and 40 patients with severe pancreatitis were randomly studied. sCD40L concentrations were measured 48 hours after admission. RESULTS: sCD40L levels were significantly higher 48 hours after admission in severe pancreatitis than in mild pancreatitis. Using a cutoff of 1 000 pg/L, the sensitivity and specificity of sCD40L to detect a severe course of the disease were 78% and 62% respectively compared to 72% and 81% for CRP. Logistic regression analysis found that CRP was the only statistically significant marker able to detect a severe course of the disease. CONCLUSION: These findings indicate that CRP remains a valuable marker to determine the severity and prognosis of acute pancreatitis whereas sCD40L levels should be assessed in further studies. PMID:16570356

Comparisons between two biochemical markers in evaluating periodontal disease severity: a cross-sectional study

PubMed Central

2014-01-01

Background The purpose of this study was to compare two biochemical markers, which have been previously used to determine the degrees of alveolar bone destruction, in evaluating periodontal disease severity. Methods The WF6 epitope of chondroitin sulfate (CS) and the alkaline phosphatase (ALP) levels were determined in gingival crevicular fluid (GCF) samples collected from patients with various degrees of disease severity, including ten patients with gingivitis (50 gingivitis sites) and 33 patients with chronic periodontitis (including gingivitis, slight, moderate, and severe periodontitis sites; n = 50 each), as well as from ten healthy volunteers (50 healthy sites) by Periopaper strips. The levels of CS and ALP were measured by an ELISA and a fluorometric assay, respectively. Results The results demonstrated low levels of CS and ALP in non-destructive and slightly destructive periodontitis sites, whereas significantly high levels of these two biomolecules were shown in moderately and severely destructive sites (p < 0.05). Although a significant difference in CS levels was found between moderate and severe periodontitis sites, no difference in ALP levels was found. Stronger correlations were found between CS levels and periodontal parameters, including probing depth, loss of clinical attachment levels, gingival index and plaque index, than between ALP levels and these parameters. Conclusions It is suggested that the CS level is a better diagnostic marker than the ALP level for evaluating distinct severity of chronic periodontitis. PMID:25174345

Dental attrition models predicting temporomandibular joint disease or masticatory muscle pain versus asymptomatic controls.

PubMed

Seligman, D A; Pullinger, A G

2006-11-01

To determine whether patients with temporomandibular joint disease or masticatory muscle pain can be usefully differentiated from asymptomatic controls using multifactorial classification tree models of attrition severity and/or rates. Measures of attrition severity and rates in patients diagnosed with disc displacement (n = 52), osteoarthrosis (n = 74), or masticatory muscle pain only (n = 43) were compared against those in asymptomatic controls (n = 132). Cross-validated classification tree models were tested for fit with sensitivity, specificity, accuracy and log likelihood accountability. The model for identifying asymptomatic controls only required the three measures of attrition severity (anterior, mediotrusive and laterotrusive posterior) to be differentiated from the patients with a 74.2 +/- 3.8% cross-validation accuracy. This compared with cross-validation accuracies of 69.7 +/- 3.7% for differentiating disc displacement using anterior and laterotrusive attrition severity, 68.7 +/- 3.9% for differentiating disc displacement using anterior and laterotrusive attrition rates, 70.9 +/- 3.3% for differentiating osteoarthrosis using anterior attrition severity and rates, 94.6 +/- 2.1% for differentiating myofascial pain using mediotrusive and laterotrusive attrition severity, and 92.0 +/- 2.1% for differentiating myofascial pain using mediotrusive and anterior attrition rates. The myofascial pain models exceeded the > or =75% sensitivity and > or =90% specificity thresholds recommended for diagnostic tests, and the asymptomatic control model approached these thresholds. Multifactorial models using attrition severity and rates may differentiate masticatory muscle pain patients from asymptomatic controls, and have some predictive value for differentiating intracapsular temporomandibular disorder patients as well.

Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

PubMed

Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

2015-01-01

Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production. © 2014 American Heart Association, Inc.

Functional connectivity in autosomal dominant and late-onset Alzheimer disease.

PubMed

Thomas, Jewell B; Brier, Matthew R; Bateman, Randall J; Snyder, Abraham Z; Benzinger, Tammie L; Xiong, Chengjie; Raichle, Marcus; Holtzman, David M; Sperling, Reisa A; Mayeux, Richard; Ghetti, Bernardino; Ringman, John M; Salloway, Stephen; McDade, Eric; Rossor, Martin N; Ourselin, Sebastien; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Weiner, Michael W; Thompson, Paul M; Fox, Nick C; Koeppe, Robert A; Jack, Clifford R; Mathis, Chester A; Oliver, Angela; Blazey, Tyler M; Moulder, Krista; Buckles, Virginia; Hornbeck, Russ; Chhatwal, Jasmeer; Schultz, Aaron P; Goate, Alison M; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; Morris, John C; Ances, Beau M

2014-09-01

Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites. For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.

Mortality among subjects with chronic obstructive pulmonary disease or asthma at two respiratory disease clinics in Ontario

PubMed Central

Finkelstein, Murray M; Chapman, Kenneth R; McIvor, R Andrew; Sears, Malcolm R

2011-01-01

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America. OBJECTIVE: To investigate mortality rates and risk factors for premature death among subjects with COPD. METHODS: Subjects were identified from the lung function testing databases of two academic respiratory disease clinics in Hamilton and Toronto, Ontario. Mortality was ascertained by linkage to the Ontario mortality registry between 1992 and 2002, inclusive. Standardized mortality ratios were computed. Poisson regression of standardized mortality ratios and proportional hazards regression were performed to examine the multivariate effect of risk factors on the standardized mortality ratios and mortality hazards. RESULTS: Compared with the Ontario population, all-cause mortality was approximately doubled among subjects with COPD, but was lower than expected among subjects with asthma. The risk of mortality in patients with COPD was related to cigarette smoking, to the presence of comorbid conditons of ischemic heart disease and diabetes, and to Global initiative for chronic Obstructive Lung Disease severity scores. Individuals living closer to traffic sources showed an elevated risk of death compared with those who lived further away from traffic sources. CONCLUSIONS: Mortality rates among subjects diagnosed with COPD were substantially elevated. There were several deaths attributed to asthma among subjects in the present study; however, overall, patients with asthma demonstrated lower mortality rates than the general population. Subjects with COPD need to be managed with attention devoted to both their respiratory disorders and related comorbidities. PMID:22187688

Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.

PubMed

Keller, San; Yang, Manshu; Treadwell, Marsha J; Hassell, Kathryn L

2017-06-02

Sickle Cell Disease (SCD) causes profound suffering and decrements in daily functioning. Demand is growing for valid and reliable measures to systematically document these effects, particularly in adults. The Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me℠, was developed for this purpose. ASCQ-Me℠ is one of four measurement systems housed within the Person-Centered Assessment Resource (PCAR), funded by the National Institutes of Health, to support clinical research. To help users select the best of these measures for adults with SCD, we evaluated and compared two PCAR systems: one designed to be "universally applicable" (the Patient-Reported Outcome Measurement Information System, PROMIS®) and one designed specifically for SCD (ASCQ-Me℠). Respondents to PROMIS and ASCQ-Me questions were 490 adults with SCD from seven geographically-disbursed clinics within the US. Data were collected for six ASCQ-Me measures (Emotional Impact, Sleep Impact, Social Impact, Stiffness Impact, Pain Impact, SCD Pain Episode Frequency and Severity) and ten PROMIS measures (Pain Impact, Pain Behavior, Physical Functioning, Anxiety, Depression, Fatigue, Satisfaction with Discretionary Social Activities, Satisfaction with Social Roles, Sleep Disturbance, and Sleep-Related Impairment). Statistical analyses, including analysis of variance and multiple linear regression, were conducted to determine the sensitivity of measures to SCD severity. SCD severity was assessed via a checklist of associated treatments and conditions. For those with the most severe SCD, PROMIS scores showed worse health compared to the general population for nine of ten health domains: the magnitude of the difference ranged 0.5 to 1.1 standard deviation units. The PROMIS domains most severely affected were Physical Functioning and Pain (Impact and Behavior). Significant differences by tertile of the SCD-MHC were shown for most PROMIS short forms and all ASCQ-Me short and fixed forms. In most models, ASCQ-Me measures explained statistically significant unique variance in SCD-MHC scores complementary to that explained by corresponding PROMIS measures. Study results supported the validity of both PROMIS and ASCQ-Me measures for use in adults with SCD. Compared to comparable PROMIS scores, most ASCQ-Me scores were better predictors of SCD disease severity, as measured by a medical history checklist. The clinical implications of these results require further investigation.

The Relative Impacts of Disease on Health Status and Capability Wellbeing: A Multi-Country Study

PubMed Central

Mitchell, Paul Mark; Al-Janabi, Hareth; Richardson, Jeff; Iezzi, Angelo; Coast, Joanna

2015-01-01

Background Evaluations of the impact of interventions for resource allocation purposes commonly focus on health status. There is, however, also concern about broader impacts on wellbeing and, increasingly, on a person's capability. This study aims to compare the impact on health status and capability of seven major health conditions, and highlight differences in treatment priorities when outcomes are measured by capability as opposed to health status. Methods The study was a cross-sectional four country survey (n = 6650) of eight population groups: seven disease groups with: arthritis, asthma, cancer, depression, diabetes, hearing loss, and heart disease and one health population ‘comparator’ group. Two simple self-complete questionnaires were used to measure health status (EQ-5D-5L) and capability (ICECAP-A). Individuals were classified by illness severity using condition-specific questionnaires. Effect sizes were used to estimate: (i) the difference in health status and capability for those with conditions, relative to a healthy population; and (ii) the impact of the severity of the condition on health status and capability within each disease group. Findings 5248 individuals were included in the analysis. Individuals with depression have the greatest mean reduction in both health (effect size, 1.26) and capability (1.22) compared to the healthy population. The effect sizes for capability for depression are much greater than for all other conditions, which is not the case for health. For example, the arthritis group effect size for health (1.24) is also high and similar to that of depression, whereas for the same arthritis group, the effect size for capability is much lower than that for depression (0.55). In terms of severity within disease groups, individuals categorised as 'mild' have similar capability levels to the healthy population (effect sizes <0.2, excluding depression) but lower health status than the healthy population (≥0.4). Conclusion Significant differences exist in the relative effect sizes across diseases when measured by health status and capability. In terms of treating morbidity, a shift in focus from health gain to capability gain would increase funding priorities for patients with depression specifically and severe illnesses more generally. PMID:26630131

Advanced Copper Composites Against Copper-Tolerant Xanthomonas perforans and Tomato Bacterial Spot.

PubMed

Strayer-Scherer, A; Liao, Y Y; Young, M; Ritchie, L; Vallad, G E; Santra, S; Freeman, J H; Clark, D; Jones, J B; Paret, M L

2018-02-01

Bacterial spot, caused by Xanthomonas spp., is a widespread and damaging bacterial disease of tomato (Solanum lycopersicum). For disease management, growers rely on copper bactericides, which are often ineffective due to the presence of copper-tolerant Xanthomonas strains. This study evaluated the antibacterial activity of the new copper composites core-shell copper (CS-Cu), multivalent copper (MV-Cu), and fixed quaternary ammonium copper (FQ-Cu) as potential alternatives to commercially available micron-sized copper bactericides for controlling copper-tolerant Xanthomonas perforans. In vitro, metallic copper from CS-Cu and FQ-Cu at 100 μg/ml killed the copper-tolerant X. perforans strain within 1 h of exposure. In contrast, none of the micron-sized copper rates (100 to 1,000 μg/ml) from Kocide 3000 significantly reduced copper-tolerant X. perforans populations after 48 h of exposure compared with the water control (P < 0.05). All copper-based treatments killed the copper-sensitive X. perforans strain within 1 h. Greenhouse studies demonstrated that all copper composites significantly reduced bacterial spot disease severity when compared with copper-mancozeb and water controls (P < 0.05). Although there was no significant impact on yield, copper composites significantly reduced disease severity when compared with water controls, using 80% less metallic copper in comparison with copper-mancozeb in field studies (P < 0.05). This study highlights the discovery that copper composites have the potential to manage copper-tolerant X. perforans and tomato bacterial spot.

Clinical course of severe colitis: a comparison between Crohn’s Disease and ulcerative colitis.

PubMed

Sinagra, E; Orlando, A; Mocciaro, F; Criscuoli, V; Oliva, L; Maisano, S; Giunta, M; La Seta, F; Solina, G; Rizzo, A G; Leone, A; Tomasello, G; Cappello, F; Cottone, M

2018-01-01

Few data are available about the clinical course of severe colonic Crohn’s disease (CD). The aim of this study is to describe the clinical course of severe Crohn’s colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohn’s colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn’s Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohn’s colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohn’s colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohn’s colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease.

Loan applications in adult patients with congenital heart disease: a French study.

PubMed

Ladouceur, Magalie; Dugardin, Bertrand; Gourdin, Stéphanie; Sidi, Daniel; Bonnet, Damien; Iserin, Laurence

2011-01-01

Improvements in the treatment of children with congenital heart disease have led to most of these patients reaching adulthood. Despite the increase in lifespan, very little is known about their quality of life - in particular, their ability to obtain a mortgage or consumer loan. To investigate the outcome of mortgage and loan applications made by adults with differential severities of congenital heart disease. Four hundred and seventy-six patients were invited to participate in a questionnaire-based interview by phone. Of these patients, one hundred and forty-two responded. Respondents were classified into three categories ('significant', 'complex' and 'mild') based on congenital heart disease severity according to the Bethesda conference. Ninety patients (64%) had applied for loans; 17 (16.5%) did not report their heart disease to the insurance company, 13 were refused insurance and 39 were asked to pay surplus fees. The imposed fees concerned patients classified in the 'significant' and 'complex' groups (P<0.0001 and P<0.003, respectively, compared with those classified in the 'mild' group). Age, sex, other diseases, cardiovascular risk factors and duration of the loan had no influence on loan application outcomes. Adults with congenital heart disease are considerably more likely to have difficulty obtaining a mortgage or loan, independent of their congenital heart disease severity. Moreover, despite an increased obtainment of a loan in patients classified as 'mild', the refusal rates were identical for patients classified as having 'significant' or 'complex' congenital heart disease, although their prognosis is different. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Performance of International Classification of Diseases-based injury severity measures used to predict in-hospital mortality and intensive care admission among traumatic brain-injured patients.

PubMed

Gagné, Mathieu; Moore, Lynne; Sirois, Marie-Josée; Simard, Marc; Beaudoin, Claudia; Kuimi, Brice Lionel Batomen

2017-02-01

The International Classification of Diseases (ICD) is the main classification system used for population-based traumatic brain injury (TBI) surveillance activities but does not contain direct information on injury severity. International Classification of Diseases-based injury severity measures can be empirically derived or mapped to the Abbreviated Injury Scale, but no single approach has been formally recommended for TBI. The aim of this study was to compare the accuracy of different ICD-based injury severity measures for predicting in-hospital mortality and intensive care unit (ICU) admission in TBI patients. We conducted a population-based retrospective cohort study. We identified all patients 16 years or older with a TBI diagnosis who received acute care between April 1, 2006, and March 31, 2013, from the Quebec Hospital Discharge Database. The accuracy of five ICD-based injury severity measures for predicting mortality and ICU admission was compared using measures of discrimination (area under the receiver operating characteristic curve [AUC]) and calibration (calibration plot and the Hosmer-Lemeshow goodness-of-fit statistic). Of 31,087 traumatic brain-injured patients in the study population, 9.0% died in hospital, and 34.4% were admitted to the ICU. Among ICD-based severity measures that were assessed, the multiplied derivative of ICD-based Injury Severity Score (ICISS-Multiplicative) demonstrated the best discriminative ability for predicting in-hospital mortality (AUC, 0.858; 95% confidence interval, 0.852-0.864) and ICU admissions (AUC, 0.813; 95% confidence interval, 0.808-0.818). Calibration assessments showed good agreement between observed and predicted in-hospital mortality for ICISS measures. All severity measures presented high agreement between observed and expected probabilities of ICU admission for all deciles of risk. The ICD-based injury severity measures can be used to accurately predict in-hospital mortality and ICU admission in TBI patients. The ICISS-Multiplicative generally outperformed other ICD-based injury severity measures and should be preferred to control for differences in baseline characteristics between TBI patients in surveillance activities or injury research when only ICD codes are available. Prognostic study, level III.

Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease.

PubMed

Lambert, Christian; Sam Narean, Janakan; Benjamin, Philip; Zeestraten, Eva; Barrick, Thomas R; Markus, Hugh S

2015-01-01

Cerebral small vessel disease (SVD) is a heterogeneous group of pathological disorders that affect the small vessels of the brain and are an important cause of cognitive impairment. The ischaemic consequences of this disease can be detected using MRI, and include white matter hyperintensities (WMH), lacunar infarcts and microhaemorrhages. The relationship between SVD disease severity, as defined by WMH volume, in sporadic age-related SVD and cortical thickness has not been well defined. However, regional cortical thickness change would be expected due to associated phenomena such as underlying ischaemic white matter damage, and the observation that widespread cortical thinning is observed in the related genetic condition CADASIL (Righart et al., 2013). Using MRI data, we have developed a semi-automated processing pipeline for the anatomical analysis of individuals with cerebral small vessel disease and applied it cross-sectionally to 121 subjects diagnosed with this condition. Using a novel combined automated white matter lesion segmentation algorithm and lesion repair step, highly accurate warping to a group average template was achieved. The volume of white matter affected by WMH was calculated, and used as a covariate of interest in a voxel-based morphometry and voxel-based cortical thickness analysis. Additionally, Gaussian Process Regression (GPR) was used to assess if the severity of SVD, measured by WMH volume, could be predicted from the morphometry and cortical thickness measures. We found significant (Family Wise Error corrected p < 0.05) volumetric decline with increasing lesion load predominately in the parietal lobes, anterior insula and caudate nuclei bilaterally. Widespread significant cortical thinning was found bilaterally in the dorsolateral prefrontal, parietal and posterio-superior temporal cortices. These represent distinctive patterns of cortical thinning and volumetric reduction compared to ageing effects in the same cohort, which exhibited greater changes in the occipital and sensorimotor cortices. Using GPR, the absolute WMH volume could be significantly estimated from the grey matter density and cortical thickness maps (Pearson's coefficients 0.80 and 0.75 respectively). We demonstrate that SVD severity is associated with regional cortical thinning. Furthermore a quantitative measure of SVD severity (WMH volume) can be predicted from grey matter measures, supporting an association between white and grey matter damage. The pattern of cortical thinning and volumetric decline is distinctive for SVD severity compared to ageing. These results, taken together, suggest that there is a phenotypic pattern of atrophy associated with SVD severity.

The relationship between infecting dose and severity of disease in reported outbreaks of Salmonella infections.

PubMed Central

Glynn, J. R.; Bradley, D. J.

1992-01-01

The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used. There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed. PMID:1468522

Lost productivity and burden of illness in cancer survivors with and without other chronic conditions.

PubMed

Dowling, Emily C; Chawla, Neetu; Forsythe, Laura P; de Moor, Janet; McNeel, Timothy; Rozjabek, Heather M; Ekwueme, Donatus U; Yabroff, K Robin

2013-09-15

Cancer survivors may experience long-term and late effects from treatment that adversely affect health and limit functioning. Few studies examine lost productivity and disease burden in cancer survivors compared with individuals who have other chronic conditions or by cancer type. We identified 4960 cancer survivors and 64,431 other individuals from the 2008-2010 Medical Expenditure Panel Survey and compared multiple measures of disease burden, including health status and lost productivity, between conditions and by cancer site for cancer survivors. All analyses controlled for the effects of age, sex, race/ethnicity, and number of comorbid conditions. Overall, in adjusted analyses in multiple models, cancer survivors with another chronic disease (heart disease or diabetes) experienced higher levels of burden compared with individuals with a history of cancer only, chronic disease only, and neither cancer, heart disease, nor diabetes across multiple measures (P < .05). Among cancer survivors, individuals with short survival cancers and multiple cancers consistently had the highest levels of burden across multiple measures (P < .0001). Cancer survivors who have another chronic disease experience more limitations and higher levels of burden across multiple measures. Limitations are particularly severe in cancer survivors with short survival cancer and multiple cancers. © 2013 American Cancer Society.

Lost Productivity and Burden of Illness in Cancer Survivors With and Without Other Chronic Conditions

PubMed Central

Dowling, Emily C.; Chawla, Neetu; Forsythe, Laura P.; de Moor, Janet; McNeel, Timothy; Rozjabek, Heather M.; Ekwueme, Donatus U.; Yabroff, K. Robin

2018-01-01

BACKGROUND Cancer survivors may experience long-term and late effects from treatment that adversely affect health and limit functioning. Few studies examine lost productivity and disease burden in cancer survivors compared with individuals who have other chronic conditions or by cancer type. METHODS We identified 4960 cancer survivors and 64,431 other individuals from the 2008–2010 Medical Expenditure Panel Survey and compared multiple measures of disease burden, including health status and lost productivity, between conditions and by cancer site for cancer survivors. All analyses controlled for the effects of age, sex, race/ethnicity, and number of comorbid conditions. RESULTS Overall, in adjusted analyses in multiple models, cancer survivors with another chronic disease (heart disease or diabetes) experienced higher levels of burden compared with individuals with a history of cancer only, chronic disease only, and neither cancer, heart disease, nor diabetes across multiple measures (P <.05). Among cancer survivors, individuals with short survival cancers and multiple cancers consistently had the highest levels of burden across multiple measures (P <.0001). CONCLUSIONS Cancer survivors who have another chronic disease experience more limitations and higher levels of burden across multiple measures. Limitations are particularly severe in cancer survivors with short survival cancer and multiple cancers. PMID:23794146

Phenotype–genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence

PubMed Central

Kashuk, Carl S.; Stone, Eric A.; Grice, Elizabeth A.; Portnoy, Matthew E.; Green, Eric D.; Sidow, Arend; Chakravarti, Aravinda; McCallion, Andrew S.

2005-01-01

The ability to discriminate between deleterious and neutral amino acid substitutions in the genes of patients remains a significant challenge in human genetics. The increasing availability of genomic sequence data from multiple vertebrate species allows inclusion of sequence conservation and physicochemical properties of residues to be used for functional prediction. In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (≥116) of disease-associated mutations has been identified among patients with Hirschsprung disease and multiple endocrine neoplasia type 2. We report the alignment of the human RET protein sequence with the orthologous sequences of 12 non-human vertebrates (eight mammalian, one avian, and three teleost species), their comparative analysis, the evolutionary topology of the RET protein, and predicted tolerance for all published missense mutations. We show that, although evolutionary conservation alone provides significant information to predict the effect of a RET mutation, a model that combines comparative sequence data with analysis of physiochemical properties in a quantitative framework provides far greater accuracy. Although the ability to discern the impact of a mutation is imperfect, our analyses permit substantial discrimination between predicted functional classes of RET mutations and disease severity even for a multigenic disease such as Hirschsprung disease. PMID:15956201

A matrix metalloproteinase 9 (MMP9) gene single nucleotide polymorphism is associated with predisposition to tick-borne encephalitis virus-induced severe central nervous system disease.

PubMed

Barkhash, Andrey V; Yurchenko, Andrey A; Yudin, Nikolay S; Ignatieva, Elena V; Kozlova, Irina V; Borishchuk, Inessa A; Pozdnyakova, Larisa L; Voevoda, Mikhail I; Romaschenko, Aida G

2018-05-01

The progression of infectious diseases depends on causative agents, the environment and the host's genetic susceptibility. To date, human genetic susceptibility to tick-borne encephalitis (TBE) virus-induced disease has not been sufficiently studied. We have combined whole-exome sequencing with a candidate gene approach to identify genes that are involved in the development of predisposition to TBE in a Russian population. Initially, six exomes from TBE patients with severe central nervous system (CNS) disease and seven exomes from control individuals were sequenced. Despite the small sample size, two nonsynonymous single nucleotide polymorphisms (SNPs) were significantly associated with TBE virus-induced severe CNS disease. One of these SNPs is rs6558394 (G/A, Pro422Leu) in the scribbled planar cell polarity protein (SCRIB) gene and the other SNP is rs17576 (A/G, Gln279Arg) in the matrix metalloproteinase 9 (MMP9) gene. Subsequently, these SNPs were genotyped in DNA samples of 150 non-immunized TBE patients with different clinical forms of the disease from two cities and 228 control randomly selected samples from the same populations. There were no statistically significant differences in genotype and allele frequencies between the case and control groups for rs6558394. However, the frequency of the rs17576 G allele was significantly higher in TBE patients with severe CNS diseases such as meningo-encephalitis (43.5%) when compared with TBE patients with milder meningitis (26.3%; P = 0.01), as well as with the population control group (32.5%; P = 0.042). The results suggest that the MMP9 gene may affect genetic predisposition to TBE in a Russian population. Copyright © 2018 Elsevier GmbH. All rights reserved.

Congruence-Incongruence Patterns in Alpha-1 Antitrypsin Deficiency Couples’ Genetic Determinist Beliefs and Perceived Control over Genes: Implications for Clinical and Public Health Genomic Communication

PubMed Central

Smith, Rachel A.; Hong, Soo Jung; Worthington, Amber

2015-01-01

Genomics makes possible the isolation of multiple genes as co-factors that increase, but do not determine, risk for many adult-onset medical conditions, including alpha-1 antitrypsin deficiency (AATD). Those diagnosed with an adult-onset medical condition, such as AATD, are often married and make decisions about testing and care as a couple. We examined genetic essentialist and threat beliefs, focusing on beliefs about the genetic contribution to disease susceptibility and severity, as well as perceptions of control related to genes and health for married couples (N =59), in which one spouse has been tested for genetic mutations associated with AATD. The intraclass correlation for spouses’ beliefs about genetic essentialism was strong and statistically significant, but the associations for their other beliefs were not. Incongruence between AATD participants and their spouses regarding genes’ influence on disease severity directly related to incongruent perceptions of control and genetic contribution to disease susceptibility. Results revealed an inverse relationship to AATD participants’ perceptions of behavioral control and a direct relationship to their beliefs about genes’ influence on disease severity. This suggests a pattern of incongruence in which AATD participants have low levels of perceived control over genes’ influence on health and high levels of perceived genetic influence on disease severity compared to spouses. With public health communication efforts lagging behind the science of genomics, insights regarding the congruence or incongruence associated with married couples’ beliefs about genes’ influence on disease afford pathways to guide clinical and public health communication about genomics. PMID:25413221

Congruence-Incongruence Patterns in Alpha-1 Antitrypsin Deficiency Couples' Genetic Determinist Beliefs and Perceived Control over Genes: Implications for Clinical and Public Health Genomic Communication.

PubMed

Parrott, Roxanne L; Smith, Rachel A; Hong, Soo Jung; Worthington, Amber

2015-06-01

Genomics makes possible the isolation of multiple genes as co-factors that increase, but do not determine, risk for many adult-onset medical conditions, including alpha-1 antitrypsin deficiency (AATD). Those diagnosed with an adult-onset medical condition, such as AATD, are often married and make decisions about testing and care as a couple. We examined genetic essentialist and threat beliefs, focusing on beliefs about the genetic contribution to disease susceptibility and severity, as well as perceptions of control related to genes and health for married couples (N =59), in which one spouse has been tested for genetic mutations associated with AATD. The intraclass correlation for spouses' beliefs about genetic essentialism was strong and statistically significant, but the associations for their other beliefs were not. Incongruence between AATD participants and their spouses regarding genes' influence on disease severity directly related to incongruent perceptions of control and genetic contribution to disease susceptibility. Results revealed an inverse relationship to AATD participants' perceptions of behavioral control and a direct relationship to their beliefs about genes' influence on disease severity. This suggests a pattern of incongruence in which AATD participants have low levels of perceived control over genes' influence on health and high levels of perceived genetic influence on disease severity compared to spouses. With public health communication efforts lagging behind the science of genomics, insights regarding the congruence or incongruence associated with married couples' beliefs about genes' influence on disease afford pathways to guide clinical and public health communication about genomics.

Gait dynamics in Pisa syndrome and Camptocormia: The role of stride length and hip kinematics.

PubMed

Tramonti, C; Di Martino, S; Unti, E; Frosini, D; Bonuccelli, U; Rossi, B; Ceravolo, R; Chisari, C

2017-09-01

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson's Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities. Copyright © 2017 Elsevier B.V. All rights reserved.

Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Su, Junjing; Manisty, Charlotte; Parker, Kim H; Simonsen, Ulf; Nielsen-Kudsk, Jens Erik; Mellemkjaer, Soren; Connolly, Susan; Lim, P Boon; Whinnett, Zachary I; Malik, Iqbal S; Watson, Geoffrey; Davies, Justin E; Gibbs, Simon; Hughes, Alun D; Howard, Luke

2017-10-31

In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Severity of menopausal symptoms and cardiovascular and osteoporosis risk factors.

PubMed

Martínez Pérez, J A; Palacios, S; Chavida, F; Pérez, M

2013-04-01

To assess whether the severity of menopausal symptoms is related to increased cardiovascular and osteoporosis risk factors, and to determine whether women with more severe menopausal symptoms present a greater percentage of osteoporosis disease. This was a cross-sectional, descriptive study encompassing women aged 45-65 years in the whole Spanish territory. The study population sample was collected through random sampling. A total of 10 514 women were included. Their sociodemographic, medical history and lifestyle data were assessed by means of a survey. The Kupperman Index was used to assess the severity of menopausal symptoms. Bone mineral density was measured by the dual X-ray absorptiometry method. The prevalences of risk factors for osteoporosis and cardiovascular disease were 67.6% and 74.8%, respectively. Women with a higher intensity of symptoms also had a greater percentage of cardiovascular (p < 0.001) and osteoporosis (p < 0.001) risk factors and suffered more from osteoporosis disease (p < 0.001). In the logistic regression analysis, those variables that contributed to the severity of menopausal symptoms were: arterial hypertension (odds ratio (OR) 2.14; 95% confidence interval (CI) 1.49-2.79; p < 0.001), dyslipidemia (OR 1.94; 95% CI 1.48-2.4; p < 0.001), obesity (OR 2.23; 95% CI 1.55-2.91; p < 0.001), family history (OR 1.38; 95% CI 1.17-1.59; p < 0.01), medication use (OR 1.12; 95% CI 0.52-1.72; p < 0.01) and osteoporosis disease (OR 3.71; 95% CI 2.9-4.52; p < 0.001). Women with more severe menopausal symptoms had a greater prevalence of cardiovascular and osteoporosis disease risk factors and suffered more from osteoporosis disease compared to those who had milder or no menopausal symptoms.

Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

PubMed

Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

2015-10-01

Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV-host interactions and of vaccine response. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute Hepatopancreatic Necrosis Disease (AHPND) related microRNAs in Litopenaeus vannamei infected with AHPND-causing strain of Vibrio parahemolyticus.

PubMed

Zheng, Zhihong; Aweya, Jude Juventus; Wang, Fan; Yao, Defu; Lun, Jingsheng; Li, Shengkang; Ma, Hongyu; Zhang, Yueling

2018-05-08

Acute hepatopancreatic necrosis disease (AHPND) has emerged as a major debilitating disease that causes massive shrimp death resulting in substantial economic losses in shrimp aquaculture. Given that several diseases and infections have been associated with microRNAs (miRNAs), we conducted a comparative transcriptomic analysis using the AHPND (VA) and non-AHPND (VN) strains of Vibrio parahemolyticus to identify miRNAs potentially involved in AHPND pathogenesis in Litopenaeus vannamei. A total of 83 miRNAs (47 upregulated and 36 downregulated) were significantly differentially expressed between the VA and VN challenged groups, while 222 target genes of these miRNAs were predicted. Functional enrichment analysis revealed that the miRNAs target genes were involved in multiple biological processes including metabolic pathways, amoebiasis, Vibrio cholerae infection etc. Finally, interaction network and qPCR (Real-time Quantitative PCR) analysis of 12 potential key AHPND-related miRNAs and their predicted target genes, revealed their possible involvement in modulating several immune-related processes in the pathogenesis of AHPND. We have shown using comparative transcriptomic analysis, miRNAs and their target genes that are responsive to AHPND V. parahemolyticus infection in shrimp, therefore suggesting their possible role in defense response to AHPND V. parahemolyticus infection.

Transgenic Wheat Expressing a Barley UDP-Glucosyltransferase Detoxifies Deoxynivalenol and Provides High Levels of Resistance to Fusarium graminearum.

PubMed

Li, Xin; Shin, Sanghyun; Heinen, Shane; Dill-Macky, Ruth; Berthiller, Franz; Nersesian, Natalya; Clemente, Thomas; McCormick, Susan; Muehlbauer, Gary J

2015-11-01

Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is a devastating disease of wheat that results in economic losses worldwide. During infection, F. graminearum produces trichothecene mycotoxins, including deoxynivalenol (DON), that increase fungal virulence and reduce grain quality. Transgenic wheat expressing a barley UDP-glucosyltransferase (HvUGT13248) were developed and evaluated for FHB resistance, DON accumulation, and the ability to metabolize DON to the less toxic DON-3-O-glucoside (D3G). Point-inoculation tests in the greenhouse showed that transgenic wheat carrying HvUGT13248 exhibited significantly higher resistance to disease spread in the spike (type II resistance) compared with nontransformed controls. Two transgenic events displayed complete suppression of disease spread in the spikes. Expression of HvUGT13248 in transgenic wheat rapidly and efficiently conjugated DON to D3G, suggesting that the enzymatic rate of DON detoxification translates to type II resistance. Under field conditions, FHB severity was variable; nonetheless, transgenic events showed significantly less-severe disease phenotypes compared with the nontransformed controls. In addition, a seedling assay demonstrated that the transformed plants had a higher tolerance to DON-inhibited root growth than nontransformed plants. These results demonstrate the utility of detoxifying DON as a FHB control strategy in wheat.

Social workers' and nurses' illness representations about Alzheimer disease: an exploratory study.

PubMed

Shinan-Altman, Shiri; Werner, Perla; Cohen, Miri

2014-01-01

Professionals' perceptions of patients' diseases (illness representations) are a major factor influencing the quality of treatment they provide. The aim of the study was to examine and compare Alzheimer disease (AD) illness representations among 2 main professional groups involved in the care of Alzheimer patients. A total of 327 nurses and social workers in Israel were asked to report their cognitive representations (dimensions of identity, cause, timeline, consequences, control, coherence, timeline cycle) and emotional representations. Knowledge about AD, demographic, and occupational characteristics were also obtained. Participants perceived AD as a chronic disease associated with severe consequences. Statistically significant differences were found between the groups, as nurses attributed psychological reasons to AD more than the social workers. Nevertheless, social workers perceived AD as more chronic with severe consequences compared with the nurses. Despite some resemblance, there were differences between the social workers and nurses regarding AD illness representations. Therefore, continuing to distribute materials to professionals regarding AD is recommended, with attention to the unique characteristics of each professional group. Furthermore, the findings encourage the development of training and support programs that will not only deal with the organizational and instrumental levels of treating AD patients but also with the assessment and consequences of professionals' illness representations.

Atopic eczema in children: another harmful sequel of divorce.

PubMed

Bockelbrink, A; Heinrich, J; Schäfer, I; Zutavern, A; Borte, M; Herbarth, O; Schaaf, B; von Berg, A; Schäfer, T

2006-12-01

Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children. Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared. Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13-0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment. Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE.

Bacterial Community Associated with Healthy and Diseased Pacific White Shrimp (Litopenaeus vannamei) Larvae and Rearing Water across Different Growth Stages.

PubMed

Zheng, Yanfen; Yu, Min; Liu, Jiwen; Qiao, Yanlu; Wang, Long; Li, Zhitao; Zhang, Xiao-Hua; Yu, Mingchao

2017-01-01

Bacterial communities are called another "organ" for aquatic animals and their important influence on the health of host has drawn increasing attention. Thus, it is important to study the relationships between aquatic animals and bacterial communities. Here, bacterial communities associated with Litopenaeus vannamei larvae at different healthy statuses (diseased and healthy) and growth stages (i.e., zoea, mysis, and early postlarvae periods) were examined using 454-pyrosequencing of the 16S rRNA gene. Bacterial communities with significant difference were observed between healthy and diseased rearing water, and several bacterial groups, such as genera Nautella and Kordiimonas could also distinguish healthy and diseased shrimp. Rhodobacteraceae was widely distributed in rearing water at all growth stages but there were several stage-specific groups, indicating that bacterial members in rearing water assembled into distinct communities throughout the larval development. However, Gammaproteobacteria , mainly family Enterobacteriaceae , was the most abundant group (accounting for more than 85%) in shrimp larvae at all growth stages. This study compared bacterial communities associated with healthy and diseased L . vannamei larvae and rearing water, and identified several health- and growth stage-specific bacterial groups, which might be provided as indicators for monitoring the healthy status of shrimp larvae in hatchery.

Equal Graph Partitioning on Estimated Infection Network as an Effective Epidemic Mitigation Measure

PubMed Central

Hadidjojo, Jeremy; Cheong, Siew Ann

2011-01-01

Controlling severe outbreaks remains the most important problem in infectious disease area. With time, this problem will only become more severe as population density in urban centers grows. Social interactions play a very important role in determining how infectious diseases spread, and organization of people along social lines gives rise to non-spatial networks in which the infections spread. Infection networks are different for diseases with different transmission modes, but are likely to be identical or highly similar for diseases that spread the same way. Hence, infection networks estimated from common infections can be useful to contain epidemics of a more severe disease with the same transmission mode. Here we present a proof-of-concept study demonstrating the effectiveness of epidemic mitigation based on such estimated infection networks. We first generate artificial social networks of different sizes and average degrees, but with roughly the same clustering characteristic. We then start SIR epidemics on these networks, censor the simulated incidences, and use them to reconstruct the infection network. We then efficiently fragment the estimated network by removing the smallest number of nodes identified by a graph partitioning algorithm. Finally, we demonstrate the effectiveness of this targeted strategy, by comparing it against traditional untargeted strategies, in slowing down and reducing the size of advancing epidemics. PMID:21799777

[Evaluation of the course of chronic obstructive lung diseases according to the classifications of the European Respiratory Society and the Global Initiative on Chronic Obstructive Lung Disease].

PubMed

Nefedov, V B; Shergina, E A; Popova, L A

2006-01-01

In 91 patients with chronic obstructive lung disease (COLD), the severity of this disease according to the Classifications of the European Respiratory Society (ERS) and the Global Initiative on Chronic Obstructive Lung Disease (GOLD) was compared with that of pulmonary dysfunction according to the data of a comprehensive study, involving the determination of bronchial patency, lung volumes, capacities, and gas-exchange function. This follows that the ERS and GOLD classifications are to be positively appraised as they provide an eligible group of patients for clinical practice in terms of the severity of pulmonary dysfunction and that of COLD. However, the concomitant clinical use of both classifications cannot be regarded as justifiable due to that there are differences in the number of detectable grades (stages) of COLD and borderline (COLD differentiating grades (stages) values of EFV1). In this connection, both classifications have approximately equally significant merits and shortcomings and it is practically impossible to give preference to one of them as the best one. The optimal way out of the established situation is to develop a new (improved) classification of the severity of COLD on the bases of these two existing classifications.

Bacterial Community Associated with Healthy and Diseased Pacific White Shrimp (Litopenaeus vannamei) Larvae and Rearing Water across Different Growth Stages

PubMed Central

Zheng, Yanfen; Yu, Min; Liu, Jiwen; Qiao, Yanlu; Wang, Long; Li, Zhitao; Zhang, Xiao-Hua; Yu, Mingchao

2017-01-01

Bacterial communities are called another “organ” for aquatic animals and their important influence on the health of host has drawn increasing attention. Thus, it is important to study the relationships between aquatic animals and bacterial communities. Here, bacterial communities associated with Litopenaeus vannamei larvae at different healthy statuses (diseased and healthy) and growth stages (i.e., zoea, mysis, and early postlarvae periods) were examined using 454-pyrosequencing of the 16S rRNA gene. Bacterial communities with significant difference were observed between healthy and diseased rearing water, and several bacterial groups, such as genera Nautella and Kordiimonas could also distinguish healthy and diseased shrimp. Rhodobacteraceae was widely distributed in rearing water at all growth stages but there were several stage-specific groups, indicating that bacterial members in rearing water assembled into distinct communities throughout the larval development. However, Gammaproteobacteria, mainly family Enterobacteriaceae, was the most abundant group (accounting for more than 85%) in shrimp larvae at all growth stages. This study compared bacterial communities associated with healthy and diseased L. vannamei larvae and rearing water, and identified several health- and growth stage-specific bacterial groups, which might be provided as indicators for monitoring the healthy status of shrimp larvae in hatchery. PMID:28769916

Prevalence of periodontal disease, its association with systemic diseases and prevention

PubMed Central

Nazir, Muhammad Ashraf

2017-01-01

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care. PMID:28539867

Prevalence of periodontal disease, its association with systemic diseases and prevention.

PubMed

Nazir, Muhammad Ashraf

2017-01-01

Periodontal diseases are prevalent both in developed and developing countries and affect about 20-50% of global population. High prevalence of periodontal disease in adolescents, adults, and older individuals makes it a public health concern. Several risk factors such as smoking, poor oral hygiene, diabetes, medication, age, hereditary, and stress are related to periodontal diseases. Robust evidence shows the association of periodontal diseases with systemic diseases such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Periodontal disease is likely to cause 19% increase in the risk of cardiovascular disease, and this increase in relative risk reaches to 44% among individuals aged 65 years and over. Type 2 diabetic individuals with severe form of periodontal disease have 3.2 times greater mortality risk compared with individuals with no or mild periodontitis. Periodontal therapy has been shown to improve glycemic control in type 2 diabetic subjects. Periodontitis is related to maternal infection, preterm birth, low birth weight, and preeclampsia. Oral disease prevention strategies should be incorporated in chronic systemic disease preventive initiatives to curtail the burden of disease in populations. The reduction in the incidence and prevalence of periodontal disease can reduce its associated systemic diseases and can also minimize their financial impact on the health-care systems. It is hoped that medical, dental practitioners, and other health-care professionals will get familiar with perio-systemic link and risk factors, and need to refer to the specialized dental or periodontal care.

MIF and D-DT are potential disease severity modifiers in male MS subjects

PubMed Central

Benedek, Gil; Meza-Romero, Roberto; Jordan, Kelley; Zhang, Ying; Nguyen, Ha; Kent, Gail; Li, Jia; Siu, Edwin; Frazer, Jenny; Piecychna, Marta; Du, Xin; Sreih, Antoine; Leng, Lin; Wiedrick, Jack; Caillier, Stacy J.; Offner, Halina; Oksenberg, Jorge R.; Yadav, Vijayshree; Bourdette, Dennis; Bucala, Richard; Vandenbark, Arthur A.

2017-01-01

Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity. Furthermore, increased MIF and D-DT levels in males with progressive disease were significantly correlated with the presence of two high-expression promoter polymorphisms located in the MIF gene, a −794CATT5–8 microsatellite repeat and a −173 G/C SNP. Conversely, mice lacking MIF or D-DT developed less-severe signs of experimental autoimmune encephalomyelitis, a murine model of MS, thus implicating both homologs as copathogenic contributors. These findings indicate that genetically controlled high MIF expression (and D-DT) promotes MS progression in males, suggesting that these two factors are sex-specific disease modifiers and raising the possibility that aggressive anti-MIF treatment of clinically isolated syndrome or RRMS males with a high-expresser genotype might slow or prevent the onset of progressive MS. Additionally, selective targeting of MIF:CD74 signaling might provide an effective, trackable therapeutic approach for MS subjects of both sexes. PMID:28923927

Retinal Mueller glial cells trigger the hallmark inflammatory process in autoimmune uveitis.

PubMed

Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Gerhards, Hartmut; Ueffing, Marius; Deeg, Cornelia A

2007-06-01

Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.

National Institutes of Health classification for chronic graft-versus-host disease predicts outcome of allo-hematopoietic stem cell transplant after fludarabine-busulfan-antithymocyte globulin conditioning regimen.

PubMed

Saillard, Colombe; Crocchiolo, Roberto; Furst, Sabine; El-Cheikh, Jean; Castagna, Luca; Signori, Alessio; Oudin, Claire; Faucher, Catherine; Lemarie, Claude; Chabannon, Christian; Granata, Angela; Blaise, Didier

2014-05-01

Abstract In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk (p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe.

Periodontal disease, tooth loss, and colorectal cancer risk: results from the Nurses’ Health Study

PubMed Central

Momen-Heravi, Fatemeh; Babic, Ana; Tworoger, Shelley S.; Zhang, Libin; Wu, Kana; Smith-Warner, Stephanie A.; Ogino, Shuji; Chan, Andrew T.; Meyerhardt, Jeffrey; Giovannucci, Edward; Fuchs, Charles; Cho, Eunyoung; Michaud, Dominique S.; Stampfer, Meir J.; Yu, Yau-Hua; Kim, David; Zhang, Xuehong

2016-01-01

Periodontal diseases including tooth loss might increase systemic inflammation, lead to immune dysregulation, and alter gut microbiota, thereby possibly influencing colorectal carcinogenesis. Few epidemiological studies have examined the association between periodontal diseases and colorectal cancer (CRC) risk. We collected information on the periodontal disease (defined as history of periodontal bone loss) and number of natural teeth in the Nurses’ Health Study. A total of 77,443 women were followed since 1992. We used Cox proportional hazard models to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) after adjustment for smoking and other known risk factors for CRC. We documented 1,165 incident CRC through 2010. Compared to women with 25–32 teeth, the multivariable HR (95% CI) for CRC for women with < 17 teeth was 1.20 (1.04–1.39). With regard to tumor site, the HRs (95% CIs) for the same comparison were 1.23 (1.01–1.51) for proximal colon cancer, 1.03 (0.76–1.38) for distal colon cancer, and 1.48 (1.07–2.05) for rectal cancer. Additionally, compared to those without periodontal disease, HRs for CRC were 0.91 (95% CI 0.74–1.12) for periodontal disease, and 1.22 (95% CI 0.91–1.63) when limited to moderate to severe periodontal disease. The results were not modified by smoking status, body mass index, or alcohol consumption. Women with fewer teeth, possibly moderate or severe periodontal disease, might be at a modest increased risk of developing CRC, suggesting a potential role of oral health in colorectal carcinogenesis. PMID:27778343

Pruning of the Pulmonary Vasculature in Asthma: The SARP Cohort.

PubMed

Ash, Samuel Y; Rahaghi, Farbod N; Come, Carolyn E; Ross, James C; Colon, Alysha G; Cardet-Guisasola, Juan Carlos; Dunican, Eleanor M; Bleecker, Eugene R; Castro, Mario; Fahy, John V; Fain, Sean B; Gaston, Benjamin M; Hoffman, Eric A; Jarjour, Nizar N; Mauger, David T; Wenzel, Sally E; Levy, Bruce D; San Jose Estepar, Raul; Israel, Elliot; Washko, George R

2018-04-19

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5mm2 in cross sectional area (BV5) and of vessels less than 10mm2 (BV10) in cross sectional area on non-contrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared to healthy controls, severe asthmatics had more pulmonary vascular pruning. Among asthmatics, those with poor asthma control had more pruning than those well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted forced expiratory volume in one second and forced vital capacity, greater peripheral and sputum eosinophilia and higher bronchoalveolar lavage SAA/LXA4, but not with low attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had a 150% greater odds of reporting an asthma exacerbation (OR 2.50; CI: 1.05, 5.98; p=0.039 for BV10/TBV), and reported 45% more asthma exacerbations during follow-up (IRR 1.45; CI: 1.02, 2.06; p=0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control and exacerbations, as well as with lung function and eosinophilia.

Prevalence and associated behavioral symptoms of depression in mild cognitive impairment and dementia due to Alzheimer's disease.

PubMed

Van der Mussele, Stefan; Bekelaar, Kim; Le Bastard, Nathalie; Vermeiren, Yannick; Saerens, Jos; Somers, Nore; Mariën, Peter; Goeman, Johan; De Deyn, Peter P; Engelborghs, Sebastiaan

2013-09-01

Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aims of this study are to determine the prevalence of significant depressive symptoms in MCI and Alzheimer's disease (AD) patients and to characterize the behavior associated with significant depressive symptoms in MCI and AD patients. A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI and 402 AD patients. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cohen-Mansfield Agitation Inventory. The presence of significant depressive symptoms was defined as a Cornell Scale for Depression in Dementia total score >7. The prevalence of significant depressive symptoms in AD patients (25%) was higher compared with MCI patients (16%) (p = 0.005). Patients with significant depressive symptoms showed an increased severity of frontal lobe symptoms, behavioral symptoms and agitation (Middelheim Frontality Score, Behave-AD and Cohen-Mansfield Agitation Inventory total scores; p < 0.001). Also, most of the individual frontal lobe and behavioral symptoms were more prevalent and severe, resulting in higher Behave-AD global scores. Mild cognitive impairment patients with depressive symptoms showed more severe behavioral symptoms and more severe verbally agitated behavior than AD patients without depressive symptoms (p < 0.001). Frontal lobe and behavioral symptoms are more prevalent and severe in MCI and AD patients with significant depressive symptoms as compared with patients without depressive symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

Micro- and nano-mechanics of osteoarthritic cartilage: The effects of tonicity and disease severity.

PubMed

Moshtagh, P R; Pouran, B; van Tiel, J; Rauker, J; Zuiddam, M R; Arbabi, V; Korthagen, N M; Weinans, H; Zadpoor, A A

2016-06-01

The present study aims to discover the contribution of glycosaminoglycans (GAGs) and collagen fibers to the mechanical properties of the osteoarthritic (OA) cartilage tissue. We used nanoindentation experiments to understand the mechanical behavior of mild and severe osteoarthritic cartilage at micro- and nano-scale at different swelling conditions. Contrast enhanced micro-computed tomography (EPIC-μCT) was used to confirm that mild OA specimens had significantly higher GAGs content compared to severe OA specimens. In micro-scale, the semi-equilibrium modulus of mild OA specimens significantly dropped after immersion in a hypertonic solution and at nano-scale, the histograms of the measured elastic modulus revealed three to four components. Comparing the peaks with those observed for healthy cartilage in a previous study indicated that the first and third peaks represent the mechanical properties of GAGs and the collagen network. The third peak shows considerably stiffer elastic modulus for mild OA samples as compared to the severe OA samples in isotonic conditions. Furthermore, this peak clearly dropped when the tonicity increased, indicating the loss of collagen (pre-) stress in the shrunk specimen. Our observations support the association of the third peak with the collagen network. However, our results did not provide any direct evidence to support the association of the first peak with GAGs. For severe OA specimens, the peak associated with the collagen network did not drop when the tonicity increased, indicating a change in the response of OA cartilage to hypertonicity, likely collagen damage, as the disease progresses to its latest stages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Single nucleotide polymorphisms in the CD40 gene associate with the disease susceptibility and severity in knee osteoarthritis in the Chinese Han population: a case-control study.

PubMed

Deng, Zhen-Han; Sun, Ming-Hua; Li, Yu-Sheng; Luo, Wei; Zhang, Fang-Jie; Tian, Jian; Wu, Ping; Xiao, Wen-Feng

2017-03-21

This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population. Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA. The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity. These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA.

Sinonasal anatomical variations: their relationship with chronic rhinosinusitis and effect on the severity of disease-a computerized tomography assisted anatomical and clinical study.

PubMed

Kaygusuz, Ahmet; Haksever, Mehmet; Akduman, Davut; Aslan, Sündüs; Sayar, Zeynep

2014-09-01

The anatomy of the sinonasal area has a very wide rage of anatomical variations. The significance of these anatomical variations in pathogenesis of rhinosinusitis, which is the commonest disease in the region, is still unclear. The aims of the study were to compare the rate of sinonasal anatomical variations with development and severity of chronic rhinosinusitis patients. CT scan of paranasal sinuses images of 99 individuals were retrospectively reviewed. 65 cases of chronic rhinosinusitis (study group) who had undergone endoscopic sinus surgery were compared with 34 cases without chronic rhinosinusitis (control group). Also in study group Lund-Mackay score of the sinus disease were calculated and compared to the rate of related anatomical variations. There were 74 (74.7 %) males and 25 (25.2 %) females with ages ranging from 13 to 70 years (mean 32.2 years). The anatomical variations recorded were: Septal deviation 47 (72.3) in study and 25 (73.5 %) in control group, concha bullosa 27 (41.5 %) in study and 18 (52.9 %) in control group, overpneumatized ethmoid bulla 17 (26.1 %) in study and 14 (41.1 %) in control group, pneumatized uncinate 3 (4.6 %) in study and 3 (8.8 %) in control group, agger nasi 42 (64.6 %) in study and 19 (55.8 %) in control group, paradoxical middle turbinates 9 (13.8 %) in study and 4 (11.7 %) in control group, Onodi cell 6 (9.2 %) in study and 2 (5.8 %) in control group, Haller's cells (infraorbital ethmoid cell) 9 (13.8 %) in study and 7 (20.5 %) in control group. None of these results were statistically significant between study and control group (p > 0.05). Lund-Mackay score (which was assumed to show the severity of the disease) of the maxillary, ethmoid and frontal sinus were calculated and compared to rate of septal deviation, concha bullosa, agger nasi cells. No significant correlation was conducted (p > 0.05). The results of study showed no statistically significant correlation between sinonasal anatomical variations and pathologies of the paranasal sinus. Also these anatomical variations did not increase the severity of pre-existing sinusitis significantly. This is a retrospective cohort study (2b).

Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

PubMed

Deck, Daniel H; Jordan, Jennifer M; Holland, Thomas L; Fan, Weihong; Wikler, Matthew A; Sulham, Katherine A; Ralph Corey, G

2016-09-01

Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. The Medicines Company, Parsippany, NJ, USA. ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).