Home monitoring of patients with Parkinson's disease via wearable technology and a web-based application.

PubMed

Patel, Shyamal; Chen, Bor-Rong; Buckley, Thomas; Rednic, Ramona; McClure, Doug; Tarsy, Daniel; Shih, Ludy; Dy, Jennifer; Welsh, Matt; Bonato, Paolo

2010-01-01

Objective long-term health monitoring can improve the clinical management of several medical conditions ranging from cardiopulmonary diseases to motor disorders. In this paper, we present our work toward the development of a home-monitoring system. The system is currently used to monitor patients with Parkinson's disease who experience severe motor fluctuations. Monitoring is achieved using wireless wearable sensors whose data are relayed to a remote clinical site via a web-based application. The work herein presented shows that wearable sensors combined with a web-based application provide reliable quantitative information that can be used for clinical decision making.

Novel Evidence-Based Classification of Cavernous Venous Occlusive Disease.

PubMed

Pathak, Ram A; Rawal, Bhupendra; Li, Zhuo; Broderick, Gregory A

2016-10-01

The primary aim of our study was to determine whether an evidence-based rationale could categorize cavernous venous occlusive disease into mild, moderate and severe erectile dysfunction. A total of 863 patients underwent color duplex Doppler ultrasound from January 2010 to June 2013 performed by a single urologist. We identified a cohort of 75 patients (8.7%) with a diagnosis of cavernous venous occlusive disease based on a unilateral resistive index less than 0.9, and right and left peak systolic velocity 35 cm per second or less after visual sexual stimulation. At a median followup of 13 months patients were evaluated for treatment efficacy. A total of 75 patients with a median age of 60 years (range 19 to 83) and a mean body mass index of 26.3 kg/m(2) (range 19.0 to 39.3) satisfied the criteria of cavernous venous occlusive disease. When substratified into tertiles, resistive index cutoffs were obtained, including mild cavernous venous occlusive disease-81.6 to 94.0, moderate disease-72.6 to 81.5 and severe disease-59.5 to 72.5. Using these 3 groups the phosphodiesterase type 5-inhibitor failure rate (p = 0.017) and SHIM (Sexual Health Inventory for Men) score categories (1 to 10 vs 11 to 20, p = 0.030) were statistically significantly different for mild, moderate and severe cavernous venous occlusive disease. Treatment satisfaction was also statistically significantly different. Penile prosthetic placement was a more common outcome among patients with erectile dysfunction and more severe cavernous venous occlusive disease. Our retrospective analysis supports a correlation between the phosphodiesterase type 5 inhibitor failure rate, SHIM score and the rate of surgical intervention using resistive index values. Our data further suggest that an evidence-based classification of cavernous venous occlusive disease by color Doppler ultrasound is possible and can triage patients to penile prosthetic placement. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Non-Dimensional Formulation of Ventricular Work-Load Severity Under Concomitant Heart Valve Disease

NASA Astrophysics Data System (ADS)

Dong, Melody; Simon-Walker, Rachael; Dasi, Lakshmi

2012-11-01

Current guidelines on assessing the severity of heart valve disease rely on dimensional disease specific measures and are thus unable to capture severity under a concomitant heart valve disease scenario. Experiments were conducted to measure ventricular work-load in an in-house in-vitro left heart simulator. In-house tri-leaflet heart valves were built and parameterized to model concomitant heart valve disease. Measured ventricular power varied non-linearly with cardiac output and mean aortic pressure. Significant data collapse could be achieved by the non-dimensionalization of ventricular power with cardiac output, fluid density, and a length scale. The dimensionless power, Circulation Energy Dissipation Index (CEDI), indicates that concomitant conditions require a significant increase in the amount of work needed to sustain cardiac function. It predicts severity without the need to quantify individual disease severities. This indicates the need for new fluid-dynamics similitude based clinical guidelines to assist patients with multiple heart valve diseases. Funded by the American Heart Association.

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Predicting and explaining inflammation in Crohn's disease patients using predictive analytics methods and electronic medical record data.

PubMed

Reddy, Bhargava K; Delen, Dursun; Agrawal, Rupesh K

2018-01-01

Crohn's disease is among the chronic inflammatory bowel diseases that impact the gastrointestinal tract. Understanding and predicting the severity of inflammation in real-time settings is critical to disease management. Extant literature has primarily focused on studies that are conducted in clinical trial settings to investigate the impact of a drug treatment on the remission status of the disease. This research proposes an analytics methodology where three different types of prediction models are developed to predict and to explain the severity of inflammation in patients diagnosed with Crohn's disease. The results show that machine-learning-based analytic methods such as gradient boosting machines can predict the inflammation severity with a very high accuracy (area under the curve = 92.82%), followed by regularized regression and logistic regression. According to the findings, a combination of baseline laboratory parameters, patient demographic characteristics, and disease location are among the strongest predictors of inflammation severity in Crohn's disease patients.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data.

PubMed

Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

2015-01-01

It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

PubMed Central

2015-01-01

Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779

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.

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.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions.

PubMed

Reddy, Rallabandi Harikrishna; Kim, Hackyoung; Cha, Seungbin; Lee, Bongsoo; Kim, Young Jun

2017-05-28

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

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.

Prevalence and severity of non-alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital.

PubMed

Marjot, T; Sbardella, E; Moolla, A; Hazlehurst, J M; Tan, G D; Ainsworth, M; Cobbold, J F L; Tomlinson, J W

2018-01-01

To define the attitudes and current clinical practice of diabetes specialists with regard to non-alcoholic fatty liver disease and, based on the results, implement an evidenced-based pathway for non-alcoholic fatty liver disease assessment. An online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre. A total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non-alcoholic fatty liver disease in people with diabetes as 50-75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non-invasive algorithm to stage the severity of non-alcoholic fatty liver disease. Implementing a local non-alcoholic fatty liver disease awareness campaign and screening strategy using pre-printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6-month period were appropriately screened for advanced fibrotic non-alcoholic fatty liver disease using the Fib-4 index; 17.9% required further investigation or assessment. The prevalence and severity of non-alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib-4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management. © 2017 Diabetes UK.

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.

Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

NASA Astrophysics Data System (ADS)

Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

2013-03-01

Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

Predicting in-hospital mortality of traffic victims: A comparison between AIS-and ICD-9-CM-related injury severity scales when only ICD-9-CM is reported.

PubMed

Van Belleghem, Griet; Devos, Stefanie; De Wit, Liesbet; Hubloue, Ives; Lauwaert, Door; Pien, Karen; Putman, Koen

2016-01-01

Injury severity scores are important in the context of developing European and national goals on traffic safety, health-care benchmarking and improving patient communication. Various severity scores are available and are mostly based on Abbreviated Injury Scale (AIS) or International Classification of Diseases (ICD). The aim of this paper is to compare the predictive value for in-hospital mortality between the various severity scores if only International Classification of Diseases, 9th revision, Clinical Modification ICD-9-CM is reported. To estimate severity scores based on the AIS lexicon, ICD-9-CM codes were converted with ICD Programmes for Injury Categorization (ICDPIC) and four AIS-based severity scores were derived: Maximum AIS (MaxAIS), Injury Severity Score (ISS), New Injury Severity Score (NISS) and Exponential Injury Severity Score (EISS). Based on ICD-9-CM, six severity scores were calculated. Determined by the number of injuries taken into account and the means by which survival risk ratios (SRRs) were calculated, four different approaches were used to calculate the ICD-9-based Injury Severity Scores (ICISS). The Trauma Mortality Prediction Model (TMPM) was calculated with the ICD-9-CM-based model averaged regression coefficients (MARC) for both the single worst injury and multiple injuries. Severity scores were compared via model discrimination and calibration. Model comparisons were performed separately for the severity scores based on the single worst injury and multiple injuries. For ICD-9-based scales, estimation of area under the receiver operating characteristic curve (AUROC) ranges between 0.94 and 0.96, while AIS-based scales range between 0.72 and 0.76, respectively. The intercept in the calibration plots is not significantly different from 0 for MaxAIS, ICISS and TMPM. When only ICD-9-CM codes are reported, ICD-9-CM-based severity scores perform better than severity scores based on the conversion to AIS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

PubMed

Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

2017-04-01

Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

Severity indices in rheumatoid arthritis: A systematic review.

PubMed

Toledano, Esther; García de Yébenes, M Jesús; González-Álvaro, Isidoro; Carmona, Loreto

2017-08-11

To identify tools designed to evaluate the severity of patients with rheumatoid arthritis (RA) in order to use them in the investigation of prognostic markers in early arthritis. We conducted a systematic review of studies that developed/validated an index for RA disease severity. They were analyzed using the COSMIN checklist to assess their methodological quality. In addition, all the variables included were evaluated for their clarity of definition, feasibility and probability of being present in each outcome during the first 2 years of the disease course. To estimate redundancy, variables were grouped by domains. After reviewing 3,519 articles, 3 studies were included. The first study, the PAS, assessed whether current and lifetime treatment with disease-modifying antirheumatic drugs and/or biologics accurately predicted RA severity, as measured by the patient-reported PAS. Treatment variables did not fully distinguish patients in the highest and lowest quartiles of PAS scores. Another severity index, the Claims-Based Index for RA Severity (CIRAS), included the variables age, sex, Felty's syndrome, number of rehabilitation and rheumatology visits, test for inflammatory markers, number of chemistry panels/platelet counts ordered and rheumatoid factor test. The correlation was low (r=0.56) with an index previously validated by the same research group, the RA medical records-based index of severity (RARBIS), with Disease Activity Score-C-reactive protein (DAS28-PCR) (r=0.07) and Multidimensional Health Assessment Questionnaire (MD-HAQ) (r=0.008). Finally, the RARBIS, used to validate the CIRAS, was devised as an RA severity index based on medical records. It includes as domains surgery, radiology, extra-articular manifestations, clinical and laboratory variables, previously chosen by an expert panel. RARBIS had a weak correlation with treatment intensity (r=0.35) and with DAS28 (r=0.41). There is no index to assess the severity of RA based on the course of the first 2 years of follow-up that is adapted to the current strategy of therapeutic management of this disease. Therefore, we believe it is reasonable to develop a new ad hoc severity index for patients with early arthritis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

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

An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls.

PubMed

Carr, Andrew R; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S; Mather, Michelle; Jimenez, Elvira E; Thompson, Paul; Mendez, Mario F

2015-11-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. Published by Elsevier Ltd.

An Investigation of Care-Based vs. Rule-Based Morality in Frontotemporal Dementia, Alzheimer’s Disease, and Healthy Controls

PubMed Central

Carr, Andrew R.; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S.; Mather, Michelle; Jimenez, Elvira E.; Thompson, Paul; Mendez, Mario F.

2015-01-01

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer’s disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. PMID:26432341

Impact of the NAP-1 strain on disease severity, mortality, and recurrence of healthcare-associated Clostridium difficile infection.

PubMed

Bauer, Karri A; Johnston, Jessica E W; Wenzler, Eric; Goff, Debra A; Cook, Charles H; Balada-Llasat, Joan-Miquel; Pancholi, Preeti; Mangino, Julie E

2017-12-01

Studies are conflicting regarding the association of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) and outcomes. We evaluated the association of NAP1 with healthcare-associated CDI disease severity, mortality, and recurrence at our academic medical center. Healthcare-associated CDI cases were identified from November 1, 2011 through January 31, 2013. Multivariable regression models were used to evaluate the associations of NAP1 with severe disease (based on the Hines VA severity score index), mortality, and recurrence. Among 5424 stool specimens submitted to the Clinical Microbiology Laboratory, 292 (5.4%) were positive for C. difficile by polymerase chain reaction (PCR) on or after hospital day 4; 70 (24%) of these specimens also tested positive for NAP1. During the study period, 247 (85%) patients had non-severe disease and 45 (15%) patients had severe disease. Among patients with non-severe disease, 65 (26%) had NAP1 and among patients with severe disease, 5 (11%) had NAP1. After controlling for potential confounders, NAP1 was not associated with an increased likelihood of severe disease (adjusted odds ratio [aOR] = 0.35; 95% confidence interval [CI], 0.13-0.93), in-hospital mortality (aOR = 1.02; 95% CI, 0.53-1.96), or recurrence (aOR = 1.16, 95% CI, 0.36-3.77). The NAP1 strain did not increase disease severity, mortality, or recurrence in this study, although the incidence of NAP1-positive healthcare associated-CDI was low. The role of strain typing in outcomes and treatment selection in patients with healthcare-associated CDI remains uncertain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tejero, Elena; Prats, Eva; Casitas, Raquel; Galera, Raúl; Pardo, Paloma; Gavilán, Adelaida; Martínez-Cerón, Elisabet; Cubillos-Zapata, Carolina; Del Peso, Luis; García-Río, Francisco

2017-08-01

Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV 1 in patients with chronic obstructive pulmonary disease (COPD). A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV 1 expressed as percentage of predicted than as z-score (area under the curve: 0.714-0.760 vs. 0.649-0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

[Toxocariasis, a neglected disease in Switzerland ?

PubMed

Duréault, Amélie; Perez Valdes, Carlos; Weber, Lalensia; Ogna, Adam; Sempoux, Christine; Manuel, Oriol; Delaloye, Julie

2017-04-12

Toxocariasis is a zoonotic disease that occurs when humans are infected by the parasites Toxocara canis or Toxocara cati. Toxocariasis is highly prevalent in tropical areas, but can also be found in industrialized countries, particularly in rural areas. Clinical presentation can range from asymptomatic infection to more severe disease. Diagnosis of toxocariasis is based on suggestive clinical findings, eosinophilia and a positive serological testing. Albendazole represents the first-line treatment, associated with corticosteroids in case of severe disease. Here we describe three clinical cases of toxocariasis in order to illustrate the clinical presentation, diagnosis and treatment of this unrecognized disease.

The Many Faces of Lupus

PubMed Central

El-Gabalawy, Hani

1990-01-01

Systemic lupus erythematosus is a multisystem disorder that presents itself in several different ways. Arthritis, dermatitis, nephritis, and pleuropericarditis are the most common features initially. Various hematologic and neuropsychiatric manifestations are also seen during the course of the disease. Anti-nuclear antibodies are the hallmark of lupus but are nonspecific and detectable in many other disorders. Once the diagnosis is established, the severity of the disease needs to be determined, in particular the extent of major organ involvement. The level of disease activity should be repeatedly estimated using clinical and laboratory parameters. Therapeutic decisions are based on disease severity and activity. Aggressive suppression of major organ inflammation and reduction of long-term toxicity are the main goals of therapy. PMID:21233973

Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection.

PubMed

Virlogeux, Victor; Fang, Vicky J; Wu, Joseph T; Ho, Lai-Ming; Peiris, J S Malik; Leung, Gabriel M; Cowling, Benjamin J

2015-09-01

Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong. We estimated the incubation period of severe acute respiratory syndrome based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.

Application of forwardchaining method to diagnosis of onion plant diseases

NASA Astrophysics Data System (ADS)

Sitanggang, Delima; Siregar, Saut D.; Situmeang, Suryani M. F.; Indra, Evta; Sagala, Ayu R.; Sihombing, Oloan; Nababan, Marlince; Pasaribu, Hendra; Damanik, Rudolf R.; Turnip, Mardi; Saragih, Rijois I. E.

2018-04-01

Red Onion is a tuber plant that is widely used by the people of Indonesia, both as herbs and herbal medicines. Onion farmers have limitations in identifying diseases that attack their crops.This disease can cause crop failure against the onion.This design begins with the creation of a knowledge base up to input-output design with forward chaining method. The results of this design can assist farmers in identifying their plant diseases. Based on diagnostic results of several methods that have been done testing can diagnose diseases contained in onion plants. With symptoms data that has been determined by the expert with the value of each symptom is different. As for the symptoms that have been determined that the leaves contain patches with a value of 0.3, White leaf spots value 0.4, Leaf spots form a purple zone if it is severe 0.5, Leaf tip of 0.2, Tubers rot 0.4. Based on the above diagnostic results then get the value of diagnosis 67% forward chaining with trotol disease type, Purple spotting.

Epidemiology of Major Non-communicable Diseases in Ethiopia: A Systematic Review

PubMed Central

Mariam, Damen Haile; Ali, Ahmed; Araya, Tekebash

2014-01-01

Impact of non-communicable diseases is not well-documented in Ethiopia. We aimed to document the prevalence and mortality associated with four major non-communicable diseases in Ethiopia: cardiovascular disease, cancer, diabetes, and chronic obstructive pulmonary disease. Associated risk factors: hypertension, tobacco-use, harmful use of alcohol, overweight/obesity, and khat-chewing were also studied. Systematic review of peer-reviewed and grey literature between 1960 and 2011 was done using PubMed search engines and local libraries to identify prevalence studies on the four diseases. In total, 32 studies were found, and half of these studies were from Addis Ababa. Two hospital-based studies reviewed the prevalence of cardiovascular disease and found a prevalence of 7.2% and 24%; a hospital-based study reviewed cancer prevalence and found a prevalence of 0.3%; two hospital-based studies reviewed diabetes prevalence and found a prevalence of 0.5% and 1.2%; and two hospital-based studies reviewed prevalence of asthma and found a prevalence of 1% and 3.5%. Few community-based studies were done on the prevalence of diabetes and chronic pulmonary obstructive disease among the population. Several studies reviewed the impact of these diseases on mortality: cardiovascular disease accounts for 24% of deaths in Addis Ababa, cancer causes 10% of deaths in the urban settings and 2% deaths in rural setting, and diabetes causes 5% and chronic obstructive pulmonary disease causes 3% of deaths. Several studies reviewed the impact of these diseases on hospital admissions: cardiovascular disease accounts for 3%-12.6% and found to have increased between 1970s and 2000s; cancer accounts for 1.1%-2.8%, diabetes accounts for 0.5%-1.2%, and chronic obstructive diseases account for 2.7%-4.3% of morbidity. Overall, the major non-communicable diseases and related risk factors are highly prevalent, and evidence-based interventions should be designed. PMID:24847587

Potential Role of Patent Foramen Ovale in Exacerbating Hypoxemia in Chronic Pulmonary Disease

PubMed Central

Aboulhosn, Jamil A.; Tobis, Jonathan M.

2017-01-01

Patent foramen ovale has been associated with multiple pulmonary diseases, such as pulmonary hypertension, platypnea-orthodeoxia syndrome, and chronic obstructive pulmonary disease. A connection between patent foramen ovale and chronic pulmonary disease was first described more than 2 decades ago in case reports associating patent foramen ovale with more severe hypoxemia than that expected based on the severity of the primary pulmonary disease. It has been suggested that patients with both chronic pulmonary disease and patent foramen ovale are subject to severe hypoxemia because of the right-to-left shunt. Furthermore, investigators have reported improved systemic oxygenation after patent foramen ovale closure in some patients with chronic pulmonary disease. This review focuses on the association between chronic pulmonary disease and patent foramen ovale and on the dynamics of a right-to-left shunt, and it considers the potential benefit of patent foramen ovale closure in patients who have hypoxemia that is excessive in relation to the degree of their pulmonary disease. PMID:28761399

Virus like particle-based vaccines against emerging infectious disease viruses.

PubMed

Liu, Jinliang; Dai, Shiyu; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2016-08-01

Emerging infectious diseases are major threats to human health. Most severe viral disease outbreaks occur in developing regions where health conditions are poor. With increased international travel and business, the possibility of eventually transmitting infectious viruses between different countries is increasing. The most effective approach in preventing viral diseases is vaccination. However, vaccines are not currently available for numerous viral diseases. Virus-like particles (VLPs) are engineered vaccine candidates that have been studied for decades. VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles. VLPs have antigenicity similar to that of the native virus, but are non-infectious as they lack key viral genetic material. VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines. Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses, which may offer effective antiviral protection. Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases. The infectious agents discussed include RNA viruses from different virus families, such as the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae, Paramyxoviridae, and Togaviridae families.

Magnetic nanoparticles-based drug and gene delivery systems for the treatment of pulmonary diseases.

PubMed

El-Sherbiny, Ibrahim M; Elbaz, Nancy M; Sedki, Mohammed; Elgammal, Abdulaziz; Yacoub, Magdi H

2017-02-01

Magnetic nanoparticles (MNPs) have gained much attention due to their unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. Due to these inherent properties, MNPs have been widely used in various biomedical applications including targeted drug delivery and hyperthermia-based therapy. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. Additionally, due to their large loading capacity and controlled release ability, several MNP-based drug delivery systems have been emerged for treatment of cystic fibrosis and lung cancer. This review provides an overview on the unique properties of MNPs and magnetic-mediated hyperthermia with emphasis on the recent biomedical applications of MNPs in treatment of both lung cancer and cystic fibrosis.

Disease burden of enterovirus 71 in rural central China: A community-based survey.

PubMed

Gan, Zheng-kai; Jin, Hui; Li, Jing-xin; Yao, Xue-jun; Zhou, Yang; Zhang, Xue-feng; Zhu, Feng-cai

2015-01-01

In recent years, the epidemics of hand, foot, and mouth disease (HFMD) centered in the Asian-Pacific region have been characterized by high morbidity and mortality. Enterovirus 71 (EV71) infections were responsible for the majority of the infections leading to severe cases of HFMD and death. This is a community-based survey aimed to estimate the disease burden of EV71 in rural central China, especially for HFMD. From 2011 to 2013, demographic and socio-economic data were gathered from 343 ill children and their parents using a structured questionnaire. We quantified the health burden of disease resulting from EV71 infection in disability-adjusted life years (DALYs). Among 343 cases, 303 had confirmed HFMD, 6 presented with herpangina, 25 presented with respiratory symptoms, and 9 presented with non-specific symptoms. The number of severe cases was 47 (including 1 death) and all of these presented with HFMD. The total cost per patient for severe HFMD, mild HFMD, herpangina, respiratory disease, and non-specific disease was $2149.47, $513.22, $53.28, $31.95, and $39.25, respectively. The overall cost of EV71-related diseases as a proportion of local farmers' per capita net income ranged from 0.18% for those with non-specific disease to 187.12% for those with severe HFMD. The loss of DALYs for the 5 forms of disease were 3.47, 1.76, 1.07, 1.44, 1.22 person-years per 1000 persons, respectively. This study provides data on cost of treatment and health burden for diseases caused by EV71, which can be used in the evaluation of EV71 vaccine cost-effectiveness.

A novel approach for predicting microRNA-disease associations by unbalanced bi-random walk on heterogeneous network.

PubMed

Luo, Jiawei; Xiao, Qiu

2017-02-01

MicroRNAs (miRNAs) play a critical role by regulating their targets in post-transcriptional level. Identification of potential miRNA-disease associations will aid in deciphering the pathogenesis of human polygenic diseases. Several computational models have been developed to uncover novel miRNA-disease associations based on the predicted target genes. However, due to the insufficient number of experimentally validated miRNA-target interactions as well as the relatively high false-positive and false-negative rates of predicted target genes, it is still challenging for these prediction models to obtain remarkable performances. The purpose of this study is to prioritize miRNA candidates for diseases. We first construct a heterogeneous network, which consists of a disease similarity network, a miRNA functional similarity network and a known miRNA-disease association network. Then, an unbalanced bi-random walk-based algorithm on the heterogeneous network (BRWH) is adopted to discover potential associations by exploiting bipartite subgraphs. Based on 5-fold cross validation, the proposed network-based method achieves AUC values ranging from 0.782 to 0.907 for the 22 human diseases and an average AUC of almost 0.846. The experiments indicated that BRWH can achieve better performances compared with several popular methods. In addition, case studies of some common diseases further demonstrated the superior performance of our proposed method on prioritizing disease-related miRNA candidates. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of Disease Case Severity Level To Determine INA CBGs Rate

NASA Astrophysics Data System (ADS)

Puspitorini, Sukma; Kusumadewi, Sri; Rosita, Linda

2017-03-01

Indonesian Case-Based Groups (INA CBGs) is case-mix payment system using software grouper application. INA CBGs consisting of four digits code where the last digits indicating the severity level of disease cases. Severity level influence by secondary diagnosis (complications and co-morbidity) related to resource intensity level. It is medical resources used to treat a hospitalized patient. Objectives of this research is developing decision support system to predict severity level of disease cases and illustrate INA CBGs rate by using data mining decision tree classification model. Primary diagnosis (DU), first secondary diagnosis (DS 1), and second secondary diagnosis (DS 2) are attributes that used as input of severity level. The training process using C4.5 algorithm and the rules will represent in the IF-THEN form. Credibility of the system analyzed through testing process and confusion matrix present the results. Outcome of this research shows that first secondary diagnosis influence significant to form severity level predicting rules from new disease cases and INA CBGs rate illustration.

Educational and motivational support service: a pilot study for mobile-phone-based interventions in patients with psoriasis.

PubMed

Balato, N; Megna, M; Di Costanzo, L; Balato, A; Ayala, F

2013-01-01

 Psoriasis is a chronic disease which requires long-term therapy. Therefore, adherence to therapy and patient motivation are key points in controlling the disease. Mobile-phone-based interventions, and in particular text messages (TM), have already been used effectively to motivate patients and improve treatment adherence in many different chronic diseases such as diabetes, cardiovascular disease and asthma. To evaluate the use of TM in improving treatment adherence and several patient outcomes such as quality of life, disease severity, patient-perceived disease severity and the patient-physician relationship. Daily TM, providing reminders and educational tools, were sent for 12 weeks to a group of 20 patients with psoriasis. At the beginning and end of the study the following assessments were performed: Psoriasis Area Severity Index (PASI), Self-Administered Psoriasis Area Severity Index (SAPASI), body surface area (BSA), Physician Global Assessment (PGA), Dermatology Life Quality Index (DLQI), evaluation of patient-physician relationship and adherence to therapy. A matched control group of 20 patients with psoriasis was used for comparison of the same outcomes. Both patient groups had similar scores for PASI, SAPASI, BSA, PGA and DLQI at baseline. However, after 12 weeks the intervention group reported a significantly better improvement of disease severity as well as quality of life, showing lower values of PASI, SAPASI, BSA, PGA and DLQI with respect to the control group (P<0·05). Moreover, adherence to therapy improved in a statistically significant way (P<0·001) whereas it remained stable in the control group. Similarly, TM interventions led to an optimization of patient-physician communication.  TM interventions seem to be a very promising tool for the long-term management of patients with psoriasis, leading to an increased compliance to therapy, positive changes in self-care behaviours and better patient-physician relationship allowing improved clinical outcomes and better control of the disease. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Quantification of liver fat: A comprehensive review.

PubMed

Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

2016-04-01

Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Severity classification of chronic obstructive pulmonary disease based on deep learning].

PubMed

Ying, Jun; Yang, Ceyuan; Li, Quanzheng; Xue, Wanguo; Li, Tanshi; Cao, Wenzhe

2017-12-01

In this paper, a deep learning method has been raised to build an automatic classification algorithm of severity of chronic obstructive pulmonary disease. Large sample clinical data as input feature were analyzed for their weights in classification. Through feature selection, model training, parameter optimization and model testing, a classification prediction model based on deep belief network was built to predict severity classification criteria raised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We get accuracy over 90% in prediction for two different standardized versions of severity criteria raised in 2007 and 2011 respectively. Moreover, we also got the contribution ranking of different input features through analyzing the model coefficient matrix and confirmed that there was a certain degree of agreement between the more contributive input features and the clinical diagnostic knowledge. The validity of the deep belief network model was proved by this result. This study provides an effective solution for the application of deep learning method in automatic diagnostic decision making.

Assessment of treatment patterns and patient outcomes before vs after implementation of a severity-based Clostridium difficile infection treatment policy.

PubMed

Jardin, C G M; Palmer, H R; Shah, D N; Le, F; Beyda, N D; Jiang, Z; Garey, K W

2013-09-01

National guidelines recommend oral vancomycin for severe Clostridium difficile infection (CDI) based on results from recent clinical trials demonstrating improved clinical outcomes. However, real-world data to support these clinical trials are scant. To compare treatment patterns and patient outcomes of those treated for CDI before and after implementation of a severity-based CDI treatment policy at a tertiary teaching hospital. This study evaluated adult patients with a positive C. difficile toxin before and after implementation of a policy where patients with severe CDI given metronidazole were switched to oral vancomycin unless contra-indicated. Patients were stratified according to disease severity using a modified published severity score. Treatment patterns based on CDI severity and rates of refractory CDI were assessed. In total, 256 patients with CDI (mean age 66 years, standard deviation 17, 52% female) were evaluated (before implementation: N = 144; after implementation: N = 112). Use of oral vancomycin for severe CDI increased significantly from 14% (N = 8) to 91% (N = 48) following implementation of the policy (P < 0.0001). Refractory disease in patients with severe CDI decreased significantly from 37% to 15% following implementation of the policy (P = 0.035). No significant differences were noted among patients with mild to moderate CDI. A severity-based CDI treatment policy at a tertiary teaching hospital increased the use of oral vancomycin and was associated with decreased rates of refractory CDI. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Clinical and financial burden of active lupus in Greece: a nationwide study.

PubMed

Bertsias, G; Karampli, E; Sidiropoulos, P; Gergianaki, I; Drosos, A; Sakkas, L; Garyfallos, A; Tzioufas, A; Vassilopoulos, D; Tsalapaki, C; Sfikakis, P; Panopoulos, S; Athanasakis, K; Perna, A; Psomali, D; Kyriopoulos, J; Boumpas, D

2016-10-01

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need. © The Author(s) 2016.

Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.

PubMed

Kawai, Toshinao; Arai, Katsuhiro; Harayama, Shizuko; Nakazawa, Yumiko; Goto, Fumihiro; Maekawa, Takanobu; Tamura, Eiichiro; Uchiyama, Toru; Onodera, Masafumi

2015-08-01

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that leads to recurrent infection and hyper-inflammation, occasionally represented by CGD-associated colitis (CGD colitis). Although clinical symptoms of CGD colitis mimic those of ulcerative colitis (UC), there is no reliable standard measurement of disease activity or standard therapeutic strategy for CGD colitis. Here, we examined the clinical manifestation of CGD colitis based on severity using a noninvasive measure of disease activity, the Pediatric Ulcerative Colitis Activity Index (PUCAI), which has been validated and widely used for pediatric UC. Sixteen of 35 CGD patients, who were diagnosed with CGD colitis based on colonoscopic and histological findings, were examined using the PUCAI. Both the PUCAI and the physician global assessment (PGA) tool were retrospectively scored by reviewing medical records. Disease activity defined by PUCAI was correlated with PGA, and increased at diagnosis of CGD colitis, especially in patients who were younger than 6 years of age (very early-onset CGD colitis: VEO-CGD colitis) when diagnosed with CGD colitis. All severe patients had a more progressive form of VEO-CGD colitis. Unlike mild and moderate patients, severe patients required multidrug therapy of corticosteroids and immunomodulator/immunosuppressants, and some were eventually treated with hematopoietic stem cell transplantation. Although the validation of PUCAI in CGD colitis should be considered for future use, our results indicate that noninvasive measures could be effective to measure disease activity and help to determine suitable treatment for CGD colitis. In patients with VEO-CGD colitis, multidrug therapy would need to be considered at an early stage on the basis of disease activity.

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

Current approaches to the management of new-onset ulcerative colitis

PubMed Central

Marchioni Beery, Renée; Kane, Sunanda

2014-01-01

Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future directions in related inflammatory bowel disease care. PMID:24872716

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report].

PubMed

Bein, T; Ehret, W; Metz, C; Hobbhahn, J; Taeger, K

1995-06-01

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States.

PubMed

Soucie, J M; Grosse, S D; Siddiqi, A-E-A; Byams, V; Thierry, J; Zack, M M; Shapiro, A; Duncan, N

2017-07-01

Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia. © 2017 John Wiley & Sons Ltd.

Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction.

PubMed

Fast, Shannon M; González, Marta C; Markuzon, Natasha

2015-01-01

Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence. The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response. The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.

Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction

PubMed Central

Fast, Shannon M.; González, Marta C.; Markuzon, Natasha

2015-01-01

Background Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence. Methodology The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response. Conclusions The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy. PMID:26288274

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

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

"Healthcare seems to vary a lot": A focus group study among parents of children with severe allergy.

PubMed

Lagercrantz, Birgitta; Persson, Åsa; Kull, Inger

2017-09-01

Living with an allergic disease has consequences for both affected children and their families. The aim of this qualitative study was to gain deeper knowledge of what life is like for families of children with severe allergic disease, in order to improve care and thereby reduce the consequences of living with a chronic disease. Four focus group interviews were performed with Swedish parents of children, aged 6-11 and 12-16 years, with severe allergic disease (from one or more allergic conditions, such as food allergy/eczema/hay fever/asthma). The participants were attending a family support weekend. Interviews were analyzed with a qualitative method. Based on parental experiences, the following themes were presented in the analysis: limitations, control, injustices, and fear and anxiety. It was evident that the families lived isolated lives and experienced different kinds of limitations. Parents felt a need to have control of their child's everyday life and described a feeling of constantly being on guard. They also suggested that understanding of the child's allergies was lacking in preschool/school and that healthcare did not provide adequate support. They felt that the same care should be offered to children and families, no matter where they lived. Based on parental experiences, having a child with severe allergic disease implies a need to constantly be on guard. In order to improve the care of children with severe allergy and their families, a more person- and family-centered approach is needed.

Incidence and admission rates for severe malaria and their impact on mortality in Africa.

PubMed

Camponovo, Flavia; Bever, Caitlin A; Galactionova, Katya; Smith, Thomas; Penny, Melissa A

2017-01-03

Appropriate treatment of life-threatening Plasmodium falciparum malaria requires in-patient care. Although the proportion of severe cases accessing in-patient care in endemic settings strongly affects overall case fatality rates and thus disease burden, this proportion is generally unknown. At present, estimates of malaria mortality are driven by prevalence or overall clinical incidence data, ignoring differences in case fatality resulting from variations in access. Consequently, the overall impact of preventive interventions on disease burden have not been validly compared with those of improvements in access to case management or its quality. Using a simulation-based approach, severe malaria admission rates and the subsequent severe malaria disease and mortality rates for 41 malaria endemic countries of sub-Saharan Africa were estimated. Country differences in transmission and health care settings were captured by use of high spatial resolution data on demographics and falciparum malaria prevalence, as well as national level estimates of effective coverage of treatment for uncomplicated malaria. Reported and modelled estimates of cases, admissions and malaria deaths from the World Malaria Report, along with predicted burden from simulations, were combined to provide revised estimates of access to in-patient care and case fatality rates. There is substantial variation between countries' in-patient admission rates and estimated levels of case fatality rates. It was found that for many African countries, most patients admitted for in-patient treatment would not meet strict criteria for severe disease and that for some countries only a small proportion of the total severe cases are admitted. Estimates are highly sensitive to the assumed community case fatality rates. Re-estimation of national level malaria mortality rates suggests that there is substantial burden attributable to inefficient in-patient access and treatment of severe disease. The model-based methods proposed here offer a standardized approach to estimate the numbers of severe malaria cases and deaths based on national level reporting, allowing for coverage of both curative and preventive interventions. This makes possible direct comparisons of the potential benefits of scaling-up either category of interventions. The profound uncertainties around these estimates highlight the need for better data.

Methamphetamine use and dental disease: results of a pilot study.

PubMed

Cretzmeyer, Margaret; Walker, Jerry; Hall, James A; Arndt, Stephan

2007-01-01

The purpose of this study was to evaluate the feasibility of using a standard dental examination to detect methamphetamine use. Data were collected from 31 patients in a hospital-based inpatient chemical dependency treatment unit using cross-sectional study design. Patients who reported current methamphetamine use were compared with patients who denied methamphetamine use on data from dental examinations and an in-depth substance use assessment. Evidence of a relationship between methamphetamine use and dental disease was not detected in this sample. Both groups had a high degree of behaviors and risk factors other than substance abuse that contributed to dental disease. Based on these data, clients who used methamphetamine could not be distinguished from those who used other substances. Both groups presented significant dental disease, however, and it may be that most, if not all, patients in this hospital-based unit had significant chronic health problems including dental disease. Although adolescent use of methamphetamine is primarily restricted to older adolescents, consequences of use are severe and early identification of drug use may forestall some of the more severe consequences.

Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity.

PubMed

van den Bergen, J C; Wokke, B H A; Hulsker, M A; Verschuuren, J J G M; Aartsma-Rus, A M

2015-03-01

Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones. Copyright © 2015 Elsevier B.V. All rights reserved.

Automatic detection and severity measurement of eczema using image processing.

PubMed

Alam, Md Nafiul; Munia, Tamanna Tabassum Khan; Tavakolian, Kouhyar; Vasefi, Fartash; MacKinnon, Nick; Fazel-Rezai, Reza

2016-08-01

Chronic skin diseases like eczema may lead to severe health and financial consequences for patients if not detected and controlled early. Early measurement of disease severity, combined with a recommendation for skin protection and use of appropriate medication can prevent the disease from worsening. Current diagnosis can be costly and time-consuming. In this paper, an automatic eczema detection and severity measurement model are presented using modern image processing and computer algorithm. The system can successfully detect regions of eczema and classify the identified region as mild or severe based on image color and texture feature. Then the model automatically measures skin parameters used in the most common assessment tool called "Eczema Area and Severity Index (EASI)," by computing eczema affected area score, eczema intensity score, and body region score of eczema allowing both patients and physicians to accurately assess the affected skin.

Animal Models of Zika Virus

PubMed Central

Bradley, Michael P; Nagamine, Claude M

2017-01-01

Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753

Animal Models of Zika Virus.

PubMed

Bradley, Michael P; Nagamine, Claude M

2017-06-01

Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian-Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model-based Zika virus research that has been performed to date.

Visual Analysis for Detection and Quantification of Pseudomonas cichorii Disease Severity in Tomato Plants.

PubMed

Rajendran, Dhinesh Kumar; Park, Eunsoo; Nagendran, Rajalingam; Hung, Nguyen Bao; Cho, Byoung-Kwan; Kim, Kyung-Hwan; Lee, Yong Hoon

2016-08-01

Pathogen infection in plants induces complex responses ranging from gene expression to metabolic processes in infected plants. In spite of many studies on biotic stress-related changes in host plants, little is known about the metabolic and phenotypic responses of the host plants to Pseudomonas cichorii infection based on image-based analysis. To investigate alterations in tomato plants according to disease severity, we inoculated plants with different cell densities of P. cichorii using dipping and syringe infiltration methods. High-dose inocula (≥ 10(6) cfu/ml) induced evident necrotic lesions within one day that corresponded to bacterial growth in the infected tissues. Among the chlorophyll fluorescence parameters analyzed, changes in quantum yield of PSII (ΦPSII) and non-photochemical quenching (NPQ) preceded the appearance of visible symptoms, but maximum quantum efficiency of PSII (Fv/Fm) was altered well after symptom development. Visible/near infrared and chlorophyll fluorescence hyperspectral images detected changes before symptom appearance at low-density inoculation. The results of this study indicate that the P. cichorii infection severity can be detected by chlorophyll fluorescence assay and hyperspectral images prior to the onset of visible symptoms, indicating the feasibility of early detection of diseases. However, to detect disease development by hyperspectral imaging, more detailed protocols and analyses are necessary. Taken together, change in chlorophyll fluorescence is a good parameter for early detection of P. cichorii infection in tomato plants. In addition, image-based visualization of infection severity before visual damage appearance will contribute to effective management of plant diseases.

Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

PubMed Central

2010-01-01

Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease. PMID:20398419

Unbiased approaches to biomarker discovery in neurodegenerative diseases

PubMed Central

Chen-Plotkin, Alice S.

2014-01-01

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia have several important features in common. They are progressive, they affect a relatively inaccessible organ, and we have no disease-modifying therapies for them. For these brain-based diseases, current diagnosis and evaluation of disease severity rely almost entirely on clinical examination, which may only be a rough approximation of disease state. Thus, the development of biomarkers – objective, relatively easily measured and precise indicators of pathogenic processes – could improve patient care and accelerate therapeutic discovery. Yet existing, rigorously tested neurodegenerative disease biomarkers are few, and even fewer biomarkers have translated into clinical use. To find new biomarkers for these diseases, an unbiased, high-throughput screening approach may be needed. In this review, I will describe the potential utility of such an approach to biomarker discovery, using Parkinson’s disease as a case example. PMID:25442938

[Valvular heart disease associated with coronary artery disease].

PubMed

Yildirir, Aylin

2009-07-01

Nowadays, age-related degenerative etiologies have largely replaced the rheumatic ones and as a natural result of this etiologic change, coronary artery disease has become associated with valvular heart disease to a greater extent. Degenerative aortic valve disease has an important pathophysiological similarity to atherosclerosis and is the leader in this association. There is a general consensus that severely stenotic aortic valve should be replaced during bypass surgery for severe coronary artery disease. For moderate degree aortic stenosis, aortic valve replacement is usually performed during coronary bypass surgery. Ischemic mitral regurgitation has recently received great attention from both diagnostic and therapeutic points of view. Ischemic mitral regurgitation significantly alters the prognosis of the patient with coronary artery disease. Severe ischemic mitral regurgitation should be corrected during coronary bypass surgery and mitral valve repair should be preferred to valve replacement. For moderate degree ischemic mitral regurgitation, many authors prefer valve surgery with coronary bypass surgery. In this review, the main characteristics of patients with coronary artery disease accompanying valvular heart disease and the therapeutic options based on individual valve pathology are discussed.

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.

Intra- and inter-observer agreement on diagnosis of Dupuytren disease, measurements of severity of contracture, and disease extent.

PubMed

Broekstra, Dieuwke C; Lanting, Rosanne; Werker, Paul M N; van den Heuvel, Edwin R

2015-08-01

Dupuytren disease (DD) is a fibrosing disease affecting the palmar aponeurosis, and is mostly treated by surgery based on measurement of severity of flexion contracture of the fingers. Literature concerning the measurement reliability is scarce. This study aimed to determine the intra- and inter-observer agreement of four variables for diagnosing DD, determining severity of contracture, and disease extent. One of them is a new measurement on the area of nodules and cords for measuring the disease extent in early disease stages. An agreement study (n = 54) was performed by two trained investigators. Agreement was calculated per finger, based on an intraclass correlation coefficient (ICC) using a latent variable model on subjects for diagnosis and Tubiana stage. For total passive extension deficit (TPED) and the area of nodules and cords, agreement was calculated with an ICC using a one-way random effects model with subject as random effect. Inter-observer agreement was very good for diagnosing DD (ICC: 95.5%-99.9%) and good to very good for classifying Tubiana stage (ICC: 73.5%-94.9%). Agreements for area and TPED were moderate (middle finger) to very good (ICC: 48.4%-98.6% and 45.0%-99.5%, respectively). Intra-observer agreement was slightly higher on average than inter-observer agreement. Overall, the intra- and inter-observer agreement in diagnosing DD, and determining the severity of flexion contracture is high. Also, the newly introduced variable area of nodules and cords has high intra- and inter-observer agreement, indicating that it is suitable to measure disease extent. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease: A FDG-PET Study.

PubMed

Lee, Jun Ho; Byun, Min Soo; Sohn, Bo Kyung; Choe, Young Min; Yi, Dahyun; Han, Ji Young; Choi, Hyo Jung; Baek, Hyewon; Woo, Jong Inn; Lee, Dong Young

2015-09-01

We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD. © The Author(s) 2015.

[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.

Plasma proteins predict conversion to dementia from prodromal disease

PubMed Central

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L.; Ashton, Nicholas J.; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-01-01

Background The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Methods Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Results Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). Conclusions We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. PMID:25012867

Plasma proteins predict conversion to dementia from prodromal disease.

PubMed

Hye, Abdul; Riddoch-Contreras, Joanna; Baird, Alison L; Ashton, Nicholas J; Bazenet, Chantal; Leung, Rufina; Westman, Eric; Simmons, Andrew; Dobson, Richard; Sattlecker, Martina; Lupton, Michelle; Lunnon, Katie; Keohane, Aoife; Ward, Malcolm; Pike, Ian; Zucht, Hans Dieter; Pepin, Danielle; Zheng, Wei; Tunnicliffe, Alan; Richardson, Jill; Gauthier, Serge; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon

2014-11-01

The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia. Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays. Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%). We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Automatic assessment of mitral regurgitation severity based on extensive textural features on 2D echocardiography videos.

PubMed

Moghaddasi, Hanie; Nourian, Saeed

2016-06-01

Heart disease is the major cause of death as well as a leading cause of disability in the developed countries. Mitral Regurgitation (MR) is a common heart disease which does not cause symptoms until its end stage. Therefore, early diagnosis of the disease is of crucial importance in the treatment process. Echocardiography is a common method of diagnosis in the severity of MR. Hence, a method which is based on echocardiography videos, image processing techniques and artificial intelligence could be helpful for clinicians, especially in borderline cases. In this paper, we introduce novel features to detect micro-patterns of echocardiography images in order to determine the severity of MR. Extensive Local Binary Pattern (ELBP) and Extensive Volume Local Binary Pattern (EVLBP) are presented as image descriptors which include details from different viewpoints of the heart in feature vectors. Support Vector Machine (SVM), Linear Discriminant Analysis (LDA) and Template Matching techniques are used as classifiers to determine the severity of MR based on textural descriptors. The SVM classifier with Extensive Uniform Local Binary Pattern (ELBPU) and Extensive Volume Local Binary Pattern (EVLBP) have the best accuracy with 99.52%, 99.38%, 99.31% and 99.59%, respectively, for the detection of Normal, Mild MR, Moderate MR and Severe MR subjects among echocardiography videos. The proposed method achieves 99.38% sensitivity and 99.63% specificity for the detection of the severity of MR and normal subjects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal Zika Virus Disease Severity, Virus Load, Prior Dengue Antibodies, and Their Relationship to Birth Outcomes.

PubMed

Halai, Umme-Aiman; Nielsen-Saines, Karin; Moreira, Maria Lopes; de Sequeira, Patricia Carvalho; Junior, Jose Paulo Pereira; de Araujo Zin, Andrea; Cherry, James; Gabaglia, Claudia Raja; Gaw, Stephanie L; Adachi, Kristina; Tsui, Irena; Pilotto, Jose Henrique; Nogueira, Rita Ribeiro; de Filippis, Ana Maria Bispo; Brasil, Patricia

2017-09-15

Congenital Zika virus (ZIKV) syndrome is a newly identified condition resulting from infection during pregnancy. We analyzed outcome data from a mother-infant cohort in Rio de Janeiro in order to assess whether clinical severity of maternal ZIKV infection was associated with maternal virus load, prior dengue antibodies, or abnormal pregnancy/infant outcomes. A clinical severity assessment tool was developed based on duration of fever, severity of rash, multisystem involvement, and duration of symptoms during ZIKV infection. ZIKV-RNA load was quantified by polymerase chain reaction (PCR) cycles in blood/ urine. Dengue immunoglobulin G (IgG) antibodies were measured at baseline. Adverse outcomes were defined as fetal loss or a live infant with grossly abnormal clinical or brain imaging findings. Regression models were used to study potential associations. 131 ZIKV-PCR positive pregnant women were scored for clinical disease severity, 6 (4.6%) had mild disease, 98 (74.8%) had moderate disease, and 27 (20.6%) severe manifestations of ZIKV infection. There were 58 (46.4%) abnormal outcomes with 9 fetal losses (7.2%) in 125 pregnancies. No associations were found between: disease severity and abnormal outcomes (P = .961; odds ratio [OR]: 1.00; 95% confidence interval [CI]: 0.796-1.270); disease severity and viral load (P = .994); viral load and adverse outcomes (P = .667; OR: 1.02; 95% CI: 0.922-1.135); or existence of prior dengue antibodies (88% subjects) with severity score, ZIKV-RNA load or adverse outcomes (P = .667; OR: 0.78; 95% CI: 0.255-2.397). Congenital ZIKV syndrome does not appear to be associated with maternal disease severity, ZIKV-RNA load at time of infection or existence of prior dengue antibodies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Obesity-related inflammation & cardiovascular disease: efficacy of a yoga-based lifestyle intervention.

PubMed

Sarvottam, Kumar; Yadav, Raj Kumar

2014-06-01

Obesity is a global health burden and its prevalence is increasing substantially due to changing lifestyle. Chronic adiposity is associated with metabolic imbalance leading to dyslipidaemia, diabetes, hypertension and cardiovascular diseases (CVD). Adipose tissue acts as an endocrine organ releasing several adipocytokines, and is associated with increased levels of tissue and circulating inflammatory biomolecules causing vascular inflammation and atherogenesis. Further, inflammation is also associated independently with obesity as well as CVD. Keeping this in view, it is possible that a reduction in weight may lead to a decrease in inflammation, resulting in CVD risk reduction, and better management of patients with CVD. Lifestyle intervention has been endorsed by several health authorities in prevention and management of chronic diseases. A yoga-based lifestyle intervention appears to be a promising option in reducing the risk for CVD as well as management of patients with CVD as it is simple to follow and cost-effective with high compliance. The efficacy of such lifestyle intervention programmes is multifaceted, and is achieved via reduction in weight, obesity-related inflammation and stress, thereby culminating into risk reduction towards several chronic diseases including CVD. In this review, the association between obesity-related inflammation and CVD, and the role of yoga-based lifestyle intervention in prevention and management of CVD are discussed.

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

Grading Severity of Productive Cough Based on Symptoms and Airflow Obstruction.

PubMed

Vazquez Guillamet, Rodrigo; Petersen, Hans; Meek, Paula; Sood, Akshay; Tesfaigzi, Yohannes

2018-04-26

The binary approach to the diagnosis of Chronic Bronchitis (CB) is a major barrier to the study of the disease. We investigated whether severity of productive cough can be graded using symptoms and presence of fixed airflow obstruction (FAO), and whether the severity correlates with health status, exposures injurious to the lung, biomarkers of inflammation, and measures of airway wall thickening. Findings from a cross-sectional sample of 1,422 participants from the Lovelace Smokers Cohort (LSC) were validated in 4,488 participants from the COPDGene cohort (COPDGene). Health status was based on the St. George's Respiratory Questionnaire, and Medical Outcomes Study 36-Item Short Form Health Survey. Circulating CC16 levels were quantified by ELISA (LSC), and airway wall thickening was measured using computed tomography (COPDGene). FAO was defined as postbronchodilator FEV 1 /FVC <0.7. The presence and duration of productive cough and presence of FAO or wheeze were graded into Healthy Smokers, Productive Cough (PC), Chronic PC, PC with Signs of Airflow Obstruction, and Chronic PC with Signs of Airflow Obstruction. In both cohorts, higher grade of severity correlated with lower health status, greater frequency of injurious exposures, greater airway wall thickening, and lower circulating CC16 levels. Further, longitudinal follow-up suggested that disease resolution can occur at every grade of severity but is more common in groups of lower severity and least common once airway remodeling develops. Therefore, severity of productive cough can be graded based on symptoms and FAO and early intervention may benefit patients by changing the natural history of disease.

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

[Celiac crisis with quadriplegia due to potassium depletion as presenting feature of celiac disease].

PubMed

Atikou, A; Rabhi, M; Hidani, H; El Alaoui Faris, M; Toloune, F

2009-06-01

Adult coeliac disease revealed by coeliac crisis and quadriplegia due to potassium depletion is an extremely rare situation. A 26-year-old woman presented with a suddenly developed weakness of all four limbs and a severe diarrhea. Authors emphasize coeliac crisis, which is a presenting feature of coeliac disease, characterized by acute diarrhea with life-threatening acid base and electrolyte abnormalities. The patient improved with correction of hypokalemia and gluten-free diet. A severe acute diarrhea with metabolic and systemic complications, the so-called coeliac crisis, is a possible presenting clinical feature of a previously undiagnosed adult celiac disease.

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

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.

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.

Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.

PubMed

Reis, Eliana A G; Hagan, José E; Ribeiro, Guilherme S; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo A; Montgomery, Ruth R; Shaw, Albert C; Ko, Albert I; Reis, Mitermayer G

2013-01-01

The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS). We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not. This study shows that severe cases of leptospirosis are differentiated from mild disease by a "cytokine storm" process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.

Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy.

PubMed

Farlow, Martin R; Grossberg, George T; Meng, Xiangyi; Olin, Jason; Somogyi, Monique

2011-12-01

The cholinesterase inhibitor rivastigmine is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline. This was a retrospective analysis of a large randomized, placebo-controlled trial (ENA713D2320). AD patients treated with 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, rivastigmine capsule (12 mg/day), or placebo were stratified according to baseline Mini-Mental State Examination (MMSE) scores: ≥7 to ≤12 (severe disease), ≥13 to ≤15 (moderately severe), ≥16 to ≤18 (moderate), or ≥19 to ≤25 (mild to moderate). Changes from baseline at Week 24 on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) were assessed. Based on baseline MMSE scores, 141, 228, 333, and 348 patients had severe, moderately severe, moderate, and mild to moderate dementia. Worsening of ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients receiving placebo were greater in patients with more severe dementia. Significant improvements versus placebo were seen with rivastigmine patch and/or capsule on ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients with severe, moderately severe, and moderate AD (all p < 0.05). However, no significant improvements were seen in rivastigmine-treated patients with mild to moderate AD. Rivastigmine benefits AD patients across dementia stages. Similar to previous cholinesterase inhibitor studies, greatest treatment effects with rivastigmine patch and capsule were seen in patients with more advanced dementia, most likely driven by greater placebo decline in this population. Copyright © 2010 John Wiley & Sons, Ltd.

Top-down approach to biological therapy of Crohn's disease.

PubMed

Hirschmann, Simon; Neurath, Markus F

2017-03-01

Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

Gaucher disease: Pseudoreversion of a disease mutation`s effects--implications for structure/function and genotype/phenotype correlations

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

Ponce, E.; Mear, J; Grabowski, G.A.

1994-09-01

Numerous mutations ({approximately}45) of the acid {beta}-glucosidase gene have been identified in patients with Gaucher disease. Many of these have been characterized by partial sequencing of cDNAs derived by RT-PCR or PCR of genomic DNA. In addition, genotype/phenotype correlations have been based on screening for known mutations. Thus, only a part of the gene is characterized in any population of affected patients. Several Gaucher disease alleles contain multiple, authentic point mutations that raises concern about conclusions based on only partial genetic characterization. Several wild-type cDNAs for acid {beta}-glucosidase have been sequenced. One contained a cloning artifact encoding R495H. We expressedmore » this cDNA and showed that the R495H enzyme had normal kinetic and stability properties. A disease-associated allele encoding R496H has been found by several groups. The close association and similarities of these two substitutions led us to question the disease casuality of the R496H allele. To evaluate this, we created and/or expressed cDNAs encoding R495, R496 (wild-type), (R495H, R496), (R495, R496H) and (R495H, R496H). The (wild-type) and (R495H, R496) enzymes had indistinguishable properties whereas the (R495, R496H) enzyme was essentially inactive. The introduction of both mutations (R495H, R496H) produced an enzyme whose activity was 25 to 50% of the wild-type. These results indicate that a pseudoreversion to a functional enzyme can occur by introducing a functionally neutral mutation together with a severe mutation. These results have major implications to structure/function and genotype/phenotype correlations in this disease.« less

Digital analysis of changes by Plasmodium vivax malaria in erythrocytes.

PubMed

Edison, Maombi; Jeeva, J B; Singh, Megha

2011-01-01

Blood samples of malaria patients (n = 30), selected based on the severity of parasitemia, were divided into low (LP), medium (MP) and high (HP) parasitemia, which represent increasing levels of the disease severity. Healthy subjects (n = 10) without any history of disease were selected as a control group. By processing of erythrocytes images their contours were obtained and from these the shape parameters area, perimeter and form factor were obtained. The gray level intensity was determined by scanning of erythrocyte along its largest diameter. A comparison of these with that of normal cells showed a significant change in shape parameters. The gray level intensity decreases with the increase of severity of the disease. The changes in shape parameters directly and gray level intensity variation inversely are correlated with the increase in parasite density due to the disease.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

PubMed

van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

2014-08-01

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

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.

Ancestry-based stratified analysis of Immunochip data identifies novel associations with celiac disease.

PubMed

Garcia-Etxebarria, Koldo; Jauregi-Miguel, Amaia; Romero-Garmendia, Irati; Plaza-Izurieta, Leticia; Legarda, Maria; Irastorza, Iñaki; Bilbao, Jose Ramon

2016-12-01

To identify candidate genes in celiac disease (CD), we reanalyzed the whole Immunochip CD cohort using a different approach that clusters individuals based on immunoancestry prior to disease association analysis, rather than by geographical origin. We detected 636 new associated SNPs (P<7.02 × 10 -07 ) and identified 5 novel genomic regions, extended 8 others previously identified and also detected 18 isolated signals defined by one or very few significant SNPs. To test whether we could identify putative candidate genes, we performed expression analyses of several genes from the top novel region (chr2:134533564-136169524), from a previously identified locus that is now extended, and a gene marked by an isolated SNP, in duodenum biopsies of active and treated CD patients, and non-celiac controls. In the largest novel region, CCNT2 and R3HDM1 were constitutively underexpressed in disease, even after gluten removal. Moreover, several genes within this region were coexpressed in patients, but not in controls. Other novel genes like KIF21B, REL and SORD also showed altered expression in active disease. Apart from the identification of novel CD loci, these results suggest that ancestry-based stratified analysis is an efficient strategy for association studies in complex diseases.

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

Determinants of health-related quality of life in psoriasis patients in Malaysia.

PubMed

Nyunt, Wint Wint Thu; Low, Wah Yun; Ismail, Rokiah; Sockalingam, Sargunan; Min, Aung Ko Ko

2015-03-01

Psoriasis is a chronic dermatological disorder that has a negative impact on quality of life (QoL). This hospital-based cross-sectional study determined factors associated with health-related QoL (HRQoL) impairment in adult psoriasis patients. HRQoL was assessed using the Dermatology Life Quality Index (DLQI). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). A total of 223 patients, aged 18 to 83 years, were recruited. For 67 (30%) patients, psoriasis had very large to extremely large effect on their life (DLQI score = 11-30). The median DLQI score was 7 (interquartile range = 7). Factors significantly associated with severe impact on HRQoL (DLQI ≥ 10) were disease severity, single status, working status, sports activities, nail dystrophy, exposed area involvement, itch, disturbed sleep, stress, and infection. The factor predictive of severe impact of psoriasis on HRQoL was disease severity. A holistic approach in the management, including psychosocial issues, is absolutely crucial for the optimal care of psoriasis patients. © 2013 APJPH.

Problem-Based Learning Used in the Context of Cardiac Rehabilitation: Different Scenes and Different Roles

ERIC Educational Resources Information Center

Hjelmfors, Lisa; Abrandt Dahlgren, Madeleine; Kärner, Anita; Tingström, Pia

2014-01-01

Several studies show that how patients have difficulties in changing lifestyle even though such changes are essential because they are suffering from a life-threatening disease. Coronary artery disease (CAD) patients met 13 times during a year and used problem-based learning (PBL) to improve their empowerment and self-efficacy in making lifestyle…

Prevalence of Periodontal Diseases in a Multicenter Cohort of Perinatally HIV-Infected and HIV-exposed and Uninfected Youth

PubMed Central

Ryder, Mark I.; Yao, Tzy-Jyun; Russell, Jonathan S.; Moscicki, Anna-Barbara; Shiboski, Caroline H.

2016-01-01

Aims To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol (AMP) study of the Pediatric HIV/AIDS cohort study (PHACS) network. Methods Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing threshold, and analyses based on more detailed whole mouth, intraoral regionally, site-based, and tooth-based criteria of bleeding on probing, plaque levels, pockets depths and clinical attachment levels. Results After adjusting for plaque control habits, and behavioral and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status. Conclusions While no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy on merits further exploration in this cohort in a longitudinal study. PMID:27801947

Risks of Death and Severe Disease in Patients With Middle East Respiratory Syndrome Coronavirus, 2012-2015.

PubMed

Rivers, Caitlin M; Majumder, Maimuna S; Lofgren, Eric T

2016-09-15

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging pathogen, first recognized in 2012, with a high case fatality risk, no vaccine, and no treatment beyond supportive care. We estimated the relative risks of death and severe disease among MERS-CoV patients in the Middle East between 2012 and 2015 for several risk factors, using Poisson regression with robust variance and a bootstrap-based expectation maximization algorithm to handle extensive missing data. Increased age and underlying comorbidity were risk factors for both death and severe disease, while cases arising in Saudi Arabia were more likely to be severe. Cases occurring later in the emergence of MERS-CoV and among health-care workers were less serious. This study represents an attempt to estimate risk factors for an emerging infectious disease using open data and to address some of the uncertainty surrounding MERS-CoV epidemiology. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Disease staging as a measure of disease severity.

PubMed

Kohyama, Jun; Fujitani, Shigeki; Umesato, Yoshimasa; Kataoka, Hitomi

2015-06-24

Disease staging, first developed in 1970, has been used to assess the levels of biological severity, defined as the risk of organ failure or death, of specific medical diseases. Because few studies to date have evaluated disease staging in Japan, a small pilot study was designed to determine whether disease staging is available and useful in actual medical practice in Japan. The relationships between disease staging and length of stay, medical costs and age were retrospectively evaluated in patients admitted to Japan Association for Development of Community Medicine - Tokyo Bay Urayasu Ichikawa Medical Center for appendicitis, type 2 diabetes mellitus, and cerebrovascular diseases from April 2012 to March 2013. Patients were easily staged based on information at the time of hospital discharge. Disease stages were found to be affected significantly by length of hospital stay and medical costs. Age also affected disease stages in patients with appendicitis. These findings indicate that disease staging was available in Japan and was affected by hospital resources, including length of hospital stay and medical costs.

Prevalence of DSM-IV Major Depression Among U.S. Military Personnel: Meta-Analysis and Simulation

DTIC Science & Technology

2012-08-01

Enduring Freedom, 3b from Operation Iraqi Freedom, and 3c from other locations. kStudies 3 and 7 to 9 are based on the mandatory Postdeployment Health (Re...physical disorders, including cardiovascular disorders (heart attack, stroke, hypertension , heart disease), respiratory disorders (COPD, asthma), diabetes...ulcer, HIV-AIDS, epilepsy or seizure disor- der, Crohn’s disease, cancer (except skin cancer), severe migraines, and extreme obesity ; and (4) severe

Falls in people with Parkinson's disease: A prospective comparison of community and home-based falls.

PubMed

Lamont, Robyn M; Morris, Meg E; Menz, Hylton B; McGinley, Jennifer L; Brauer, Sandra G

2017-06-01

Falls are common and debilitating in people with Parkinson's disease (PD) and restrict participation in daily activities. Understanding circumstances of falls in the community and at home may assist clinicians to target therapy more effectively. To compare the characteristics of community and home fallers and the circumstances that contribute to falls in people living with PD. People with mild-moderately severe PD (n=196) used a daily falls diary and telephone hotline to report prospectively the occurrence, location and circumstances of falls over 14 months. 62% of people with PD fell, with most falling at least once in the community. Compared to people who fell at home, the community-only fallers had shorter durations of PD (p=0.012), less severe disease (p=0.008) and reported fewer falls in the year prior to the study (p=0.003). Most falls occurred while people were ambulant, during postural transitions and when medication was working well. Community-based falls were frequently attributed to environmental factors such as challenging terrains (p<0.001), high attention demands (p=0.029), busy or cluttered areas (p<0.001) and tasks requiring speed (p=0.020). Physical loads were more often present in home than community-based falls (p=0.027). Falls that occur in the community typically affect people with earlier PD and less severe disease than home-based falls. Individuals experiencing community-based falls may benefit from physiotherapy to manage challenging environments and high attention demands. Copyright © 2017 Elsevier B.V. All rights reserved.

Oligonucleotide-based therapy for neurodegenerative diseases.

PubMed

Magen, Iddo; Hornstein, Eran

2014-10-10

Molecular genetics insight into the pathogenesis of several neurodegenerative diseases, such as Alzheimer׳s disease, Parkinson׳s disease, Huntington׳s disease and amyotrophic lateral sclerosis, encourages direct interference with the activity of neurotoxic genes or the molecular activation of neuroprotective pathways. Oligonucleotide-based therapies are recently emerging as an efficient strategy for drug development and these can be employed as new treatments of neurodegenerative states. Here we review advances in this field in recent years which suggest an encouraging assessment that oligonucleotide technologies for targeting of RNAs will enable the development of new therapies and will contribute to preservation of brain integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Epidemiology of chronic obstructive pulmonary disease: a population-based study in Krasnoyarsk region, Russia.

PubMed

Artyukhov, Ivan P; Arshukova, Irina L; Dobretsova, Elena A; Dugina, Tatyana A; Shulmin, Andrey V; Demko, Irina V

2015-01-01

Krasnoyarsk region is a territory with the widespread risk factors for chronic obstructive pulmonary disease (COPD) such as tobacco smoke, air pollution, and occupational exposure. An assessment of COPD prevalence based on medical diagnosis statistics underestimates the true COPD prevalence. This study aims to evaluate how medical examinations may increase the accuracy of estimates of COPD prevalence. True COPD prevalence was estimated as a number of patients with the established disease diagnosis supplemented by the additional disease cases detected during medical examinations per 1,000 inhabitants of the region. Official medical statistics data and the data collected from the Global Alliance against Chronic Respiratory Diseases program 2011 among 15,000 inhabitants of the region aged 18 years and older were analyzed. This study revealed the COPD cases without official medical diagnosis. The true prevalence of COPD is estimated to be two times higher than the prevalence estimates based on medical diagnosis statistics. Undiagnosed and untreated cases of COPD result in severe COPD forms as well as addition of severe comorbidities. Because of this, there is an increase in the index of potential years of life lost. Conducting special medical examinations may increase the number of COPD cases detected at the early stages of the disease. This, in turn, may reduce the overall burden of the disease for the population of the region.

Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).

PubMed

Biancone, Livia; Annese, Vito; Ardizzone, Sandro; Armuzzi, Alessandro; Calabrese, Emma; Caprioli, Flavio; Castiglione, Fabiana; Comberlato, Michele; Cottone, Mario; Danese, Silvio; Daperno, Marco; D'Incà, Renata; Frieri, Giuseppe; Fries, Walter; Gionchetti, Paolo; Kohn, Anna; Latella, Giovanni; Milla, Monica; Orlando, Ambrogio; Papi, Claudio; Petruzziello, Carmelina; Riegler, Gabriele; Rizzello, Fernando; Saibeni, Simone; Scribano, Maria Lia; Vecchi, Maurizio; Vernia, Piero; Meucci, Gianmichele

2017-04-01

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[The relationship between extraesophageal manifestations of gastroesophageal reflux disease, the frequency of heartburn and severity of oesophagitis].

PubMed

2011-01-01

We performed clinico-epidemiologic screening for the heartburn in a representative sample from a total of 1138 subjects and for oesophagitis from 371 ones. In a separate study 120 patients were divided into groups differing in the severity of oesophagitis based on the Savary-Miller classification. The extraesophageal manifestations were diagnosed by clinical and instrumental methods. The close relationship of these manifestations with heartburn and oesophagitis was more pronounced in men than in women. Enhanced severity of the lesions in eosophageal mucosa in patients with oesophagitis was related to increased frequency of ENT diseases and cardialgia but not respiratory disorders. The data obtained give evidence of direct association of heartburn and eosophagitis with coughing, ENT diseases and cardialgia.

DiseaseConnect: a comprehensive web server for mechanism-based disease–disease connections

PubMed Central

Liu, Chun-Chi; Tseng, Yu-Ting; Li, Wenyuan; Wu, Chia-Yu; Mayzus, Ilya; Rzhetsky, Andrey; Sun, Fengzhu; Waterman, Michael; Chen, Jeremy J. W.; Chaudhary, Preet M.; Loscalzo, Joseph; Crandall, Edward; Zhou, Xianghong Jasmine

2014-01-01

The DiseaseConnect (http://disease-connect.org) is a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. The traditional disease classification system groups diseases with similar clinical symptoms and phenotypic traits. Thus, diseases with entirely different pathologies could be grouped together, leading to a similar treatment design. Such problems could be avoided if diseases were classified based on their molecular mechanisms. Connecting diseases with similar pathological mechanisms could inspire novel strategies on the effective repositioning of existing drugs and therapies. Although there have been several studies attempting to generate disease connectivity networks, they have not yet utilized the enormous and rapidly growing public repositories of disease-related omics data and literature, two primary resources capable of providing insights into disease connections at an unprecedented level of detail. Our DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease–disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug–disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments. PMID:24895436

Effect of a rehabilitation-based chronic disease management program targeting severe COPD exacerbations on readmission patterns.

PubMed

Lalmolda, C; Coll-Fernández, R; Martínez, N; Baré, M; Teixidó Colet, M; Epelde, F; Monsó, E

2017-01-01

Pulmonary rehabilitation (PR) is recommended after a severe COPD exacerbation, but its short- and long-term effects on health care utilization have not been fully established. The aims of this study were to evaluate patient compliance with a chronic disease management (CDM) program incorporating home-based exercise training as the main component after a severe COPD exacerbation and to determine its effects on health care utilization in the following year. COPD patients with a severe exacerbation were included in a case-cohort study at admission. An intervention group participated in a nurse-supervised CDM program during the 2 months after discharge, comprising of home-based PR with exercise components directly supervised by a physiotherapist, while the remaining patients followed usual care. Nineteen of the twenty-one participants (90.5%) were compliant with the CDM program and were compared with 29 usual-care patients. Compliance with the program was associated with statistically significant reductions in admissions due to respiratory disease in the following year (median [interquartile range]: 0 [0-1] vs 1 [0-2.5]; P =0.022) and in days of admission (0 [0-7] vs 7 [0-12]; P =0.034), and multiple linear regression analysis confirmed the protective effect of the CDM program (β coefficient -0.785, P =0.014, and R 2 =0.219). A CDM program incorporating exercise training for COPD patients without limiting comorbidities after a severe exacerbation achieves high compliance and reduces admissions in the year following after the intervention.

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

PubMed

Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of disease risk probability and disease type on interest in clinic-based versus direct-to-consumer genetic testing services.

PubMed

Sherman, Kerry; Shaw, Laura-Kate; Champion, Katrina; Caldeira, Fernanda; McCaskill, Margaret

2015-10-01

The effect of disease-specific cognitions on interest in clinic-based and direct-to-consumer (DTC) genetic testing was assessed. Participants (N = 309) responded to an online hypothetical scenario and received genetic testing-related messages that varied by risk probability (25, 50, 75 %) and disease type (Alzheimer's disease vs. Type 2 Diabetes). Post-manipulation interest increased for both testing types, but was greater for clinic-based testing. Interest was greater for Type 2 Diabetes than for Alzheimer's disease, the latter perceived as more severe and likely, and less treatable and preventable. For DTC testing only, participants allocated to the high risk condition (75 %) had greater testing interest than those in the low (25 %) category. DTC testing is perceived as a viable, but less preferred, option compared with clinic-based testing. Particularly when considering DTC genetic testing, there is a need to emphasize subjective disease-related perceptions, including risk probability.

Vocal symptoms in Parkinson disease treated with levodopa. A case report.

PubMed

Schley, W S; Fenton, E; Niimi, S

1982-01-01

This is a report of a patient with unusually severe hoarseness in the absence of vocal fold pathology demonstrating Parkinson disease as one of the neurological diseases in which vocal symptoms occur. Although it is classifiably a severe, progressive, degenerative disorder, the popularity of pharmacotherapy for Parkinson disease during the past decade has resulted in improved functionality for an undetermined course of time in most patients. The classically described deterioration of speech ad voice may develop in a variant manner difficult to distinguish as disease-related, as this case report illustrates. An explanation of the hoarseness based on dyssynchronous vocal fold motion related to the disease is suggested by the acoustic methods (spectrography, waveform analysis) used in this study, and supported by strobe light laryngoscopy. This conclusion is important because of the extremely high incidences of varying degrees of hoarseness reported in recent studies of Parkinson disease.

[From chronic disease to multimorbidity: Which impact on organization of health care].

PubMed

Belche, Jean-Luc; Berrewaerts, Marie-Astrid; Ketterer, Frédéric; Henrard, Gilles; Vanmeerbeek, Marc; Giet, Didier

2015-11-01

Healthcare systems are concerned with the growing prevalence of chronic diseases. Single disease approach, based on the Chronic Care Model, is known to improve specific indicators for the targeted disease. However, the co-existence of several chronic disease, or multimorbidity, within a same patient is the most frequent situation. The fragmentation of care, as consequence of the single disease approach, has negative impact on the patient and healthcare professionals. A person centred approach is a method addressing the combination of health issues of each patient. The coordination and synthesis role is key to ensure continuity of care for the patient within a network of healthcare professionals from several settings of care. This function is the main characteristic of an organized first level of care. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Commonly used severity scores are not good predictors of mortality in sepsis from severe leptospirosis: a series of ten patients.

PubMed

Velissaris, Dimitrios; Karanikolas, Menelaos; Flaris, Nikolaos; Fligou, Fotini; Marangos, Markos; Filos, Kriton S

2012-01-01

Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality. Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee. Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors. Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings.

Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

PubMed

Gotsman, Israel; Stabholz, Ayala; Planer, David; Pugatsch, Thea; Lapidus, Ludmila; Novikov, Yelena; Masrawa, Siham; Soskolne, Aubrey; Lotan, Chaim

2008-07-01

Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. To determine the relationship between inflammatory markers and the angiographic severity of CAD. We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

PubMed Central

Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

2012-01-01

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

Vaccination against Lyme disease: Are we ready for it?

PubMed

Kaaijk, Patricia; Luytjes, Willem

2016-03-03

Lyme disease is the most common tick-borne illness in the Northern hemisphere and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. A first sign of Borrelia infection is a circular skin rash, erythema migrans, but it can develop to more serious manifestations affecting skin, nervous system, joints, and/or heart. The marked increase in Lyme disease incidence over the past decades, the severity of the disease, and the associated high medical costs of, in particular, the persistent forms of Lyme disease requires adequate measures for control. Vaccination would be the most effective intervention for prevention, but at present no vaccine is available. In the 1990s, 2 vaccines against Lyme disease based on the OspA protein from the predominant Borrelia species of the US showed to be safe and effective in clinical phase III studies. However, failed public acceptance led to the demise of these monovalent OspA-based vaccines. Nowadays, public seem to be more aware of the serious health problems that Lyme disease can cause and seem more ready for the use of a broadly protective vaccine. This article discusses several aspects that should be considered to enable the development and implementation of a vaccine to prevent Lyme disease successfully.

Vaccination against Lyme disease: Are we ready for it?

PubMed Central

Kaaijk, Patricia; Luytjes, Willem

2016-01-01

Abstract Lyme disease is the most common tick-borne illness in the Northern hemisphere and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. A first sign of Borrelia infection is a circular skin rash, erythema migrans, but it can develop to more serious manifestations affecting skin, nervous system, joints, and/or heart. The marked increase in Lyme disease incidence over the past decades, the severity of the disease, and the associated high medical costs of, in particular, the persistent forms of Lyme disease requires adequate measures for control. Vaccination would be the most effective intervention for prevention, but at present no vaccine is available. In the 1990s, 2 vaccines against Lyme disease based on the OspA protein from the predominant Borrelia species of the US showed to be safe and effective in clinical phase III studies. However, failed public acceptance led to the demise of these monovalent OspA-based vaccines. Nowadays, public seem to be more aware of the serious health problems that Lyme disease can cause and seem more ready for the use of a broadly protective vaccine. This article discusses several aspects that should be considered to enable the development and implementation of a vaccine to prevent Lyme disease successfully. PMID:26337648

Advances in Reprogramming-Based Study of Neurologic Disorders

PubMed Central

Baldwin, Kristin K.

2015-01-01

The technology to convert adult human non-neural cells into neural lineages, through induced pluripotent stem cells (iPSCs), somatic cell nuclear transfer, and direct lineage reprogramming or transdifferentiation has progressed tremendously in recent years. Reprogramming-based approaches aimed at manipulating cellular identity have enormous potential for disease modeling, high-throughput drug screening, cell therapy, and personalized medicine. Human iPSC (hiPSC)-based cellular disease models have provided proof of principle evidence of the validity of this system. However, several challenges remain before patient-specific neurons produced by reprogramming can provide reliable insights into disease mechanisms or be efficiently applied to drug discovery and transplantation therapy. This review will first discuss limitations of currently available reprogramming-based methods in faithfully and reproducibly recapitulating disease pathology. Specifically, we will address issues such as culture heterogeneity, interline and inter-individual variability, and limitations of two-dimensional differentiation paradigms. Second, we will assess recent progress and the future prospects of reprogramming-based neurologic disease modeling. This includes three-dimensional disease modeling, advances in reprogramming technology, prescreening of hiPSCs and creating isogenic disease models using gene editing. PMID:25749371

Rare lung disease research: strategies for improving identification and recruitment of research participants.

PubMed

Gupta, Samir; Bayoumi, Ahmed M; Faughnan, Marie E

2011-11-01

Research in rare lung diseases faces methodologic limitations by virtue of the small number of participants available to be studied. We explored several strategies that may improve researchers' ability to identify and recruit research participants with rare lung diseases. We provide an overview of strategies based on available evidence, previously used approaches, and reasoning. First, disease detection is generally poor and may be improved through strategies targeted at primary care practitioners or directly at patients, thus increasing the pool of patients available for research studies. Next, standardization of case definitions in rare lung diseases is often lacking, hindering research recruitment efforts because of confusion over appropriate recruitment criteria. Expert consensus statements can enhance both clinical care and research recruitment by standardizing definitions. Finally, recruitment strategies using rare lung disease registries, clinical research networks, novel Internet-based direct patient recruitment approaches, and patient organizations may facilitate recruitment of patients with rare lung diseases. In summary, although several strategies for improving the identification and recruitment of research participants with rare lung diseases have been proposed, published examples are few. Objective measurement and reporting of novel recruitment methods and collaboration among researchers facing the same limitations across various rare lung diseases are required. Advancements in this area are vital to the design and performance of much-needed robust clinical studies across the spectrum of rare lung diseases.

[Psychiatric disorders in patients with Cushing's disease before and after neurosurgery].

PubMed

Gnjidiae, Zivko; Karloviae, Dalibor; Buljan, Danijel; Malencia, Masa; Kovak-Mufiae, Ana; Kostanjsak, Lidija

2011-01-01

Cushing's disease which is a consequence of ACTH-secreting pituitary adenoma leads to hypercortisolism. Cushing's disease is associated with several psychiatric disturbances. The aim of the present study was to identify which psychiatric disorders were present in patients with Cushing's disease over a 2-year period and to monitor their general psychiatric condition. Additionally, the study aimed to examine the relationship between the duration of Cushing's disease, and the severity of psychiatric conditions based on psychiatric rating scales. The study included 39 patients with Cushing's disease that underwent neurosurgery for ACTH-secreting pituitary adenomas. The transsphenoidal approach (the standard microsurgery technique) was performed in all patients. ACTH-secreting pituitary adenomas were confirmed based on immunohistochemistry in all patients. Psychiatric conditions in the patients were identified using the Clinical Global Impression Scale (CGI) and ICD 10 diagnostic criteria at 3 time points: prior to surgery, and 6 and 48 months post surgery. The Cushing's disease patients exhibited statistically significant improvement in their psychiatric condition, according to the CGI, 6 and 48 months post surgery. There wasn't any significant correlation between the duration of Cushing's disease and psychiatric status, as measured by the CGI prior to surgery, 6 months post surgery, or 48 months post surgery. Patients with Cushing's disease had a significant level psychiatric disturbance that remitted after surgery. There wasn't a significant correlation between the duration of Cushing's disease and psychiatric status.

Immunopathogenesis of Thyroid Eye Disease: Emerging Paradigms

PubMed Central

Naik, Vibhavari M; Naik, Milind N; Goldberg, Robert A; Smith, Terry J; Douglas, Raymond S

2009-01-01

Graves disease represents a systemic autoimmune process targeting the thyroid, orbit, and pretibial skin. The thyroid dysfunction is treatable, but no consistently effective medical therapy has yet been described for the orbital manifestations of Graves disease, also known as thyroid-associated ophthalmopathy or thyroid eye disease. Several autoantigens are potentially relevant to the pathogenesis of thyroid eye disease. Activating antibodies generated against the thyrotropin receptor can be detected in a majority of patients, and these drive hyperthyroidism. However, stimulating antibodies against the insulin-like growth factor-1 receptor (IGF-1R) may also play a role in the extra-thyroid manifestations of GD. IGF-1R is over-expressed by orbital fibroblasts derived from patients with TED, while IGF-1R+ T and IGF-1R+ B cells are considerably more frequent in GD. Actions of several cytokines and the molecular interplay peculiar to the orbit appear to provoke the inflammation, fat expansion, and deposition of excessive extracellular matrix molecules in thyroid eye disease. Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis. PMID:20385333

Clinical penetrance in hereditary hemochromatosis: estimates of the cumulative incidence of severe liver disease among HFE C282Y homozygotes.

PubMed

Grosse, Scott D; Gurrin, Lyle C; Bertalli, Nadine A; Allen, Katrina J

2018-04-01

Iron overload (hemochromatosis) can cause serious, symptomatic disease that is preventable if detected early and managed appropriately. The leading cause of hemochromatosis in populations of predominantly European ancestry is homozygosity of the C282Y variant in the HFE gene. Screening of adults for iron overload or associated genotypes is controversial, largely because of a belief that severe phenotypes are uncommon, although cascade testing of first-degree relatives of patients is widely endorsed. We contend that severe liver disease (cirrhosis or hepatocellular cancer) is not at all uncommon among older males with hereditary hemochromatosis. Our review of the published data from a variety of empirical sources indicates that roughly 1 in 10 male HFE C282Y homozygotes is likely to develop severe liver disease during his lifetime unless iron overload is detected early and treated. New evidence from a randomized controlled trial of treatment allows for evidence-based management of presymptomatic patients. Although population screening for HFE C282Y homozygosity faces multiple barriers, a potentially effective strategy for increasing the early detection and prevention of clinical iron overload and severe disease is to include HFE C282Y homozygosity in lists of medically actionable gene variants when reporting the results of genome or exome sequencing.

Evidence-based practice in Behçet’s disease: identifying areas of unmet need for 2014

PubMed Central

2014-01-01

Background Behçet’s Disease (BD) is characterized by a relapsing-remitting course, with symptoms of varying severity across almost all organ systems. There is a diverse array of therapeutic options with no universally accepted treatment regime, and it is thus important that clinical practice is evidence-based. We reviewed all currently available literature describing management of BD, and investigated whether evidence-based practice is possible for all disease manifestations, and assessed the range of therapeutic options tested. Methods We conducted an internet search of all literature describing management of BD up to August 2013, including pharmacological and non-pharmacological interventions. We recorded treatment options investigated and disease manifestations reported as primary and secondary study outcomes. Quality of data was assessed according to the Scottish Intercollegiate Guideline Network (SIGN) hierarchy of evidence. Results Whilst there is much literature describing treatment of ocular and mucocutaneous disease, there is little to guide management of rheumatoid, cardiovascular and neurological disease. This broadly reflects the prevalence of disease manifestations of BD, but not the severity. Biologic therapies are the most commonly investigated intervention. The proportion of SIGN-1 graded studies is declining, and there are no SIGN-1 graded studies investigating neurological or gastrointestinal manifestations of BD. Conclusions This is the first study to investigate trends in published literature for management of BD over time. It identifies neurological, cardiovascular and gastro-intestinal disease as particular areas of unmet need and suggests that overall quality of evidence is declining. Future research should be designed to address these areas of insufficiency to facilitate evidence-based practice in BD. PMID:24475935

Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases.

PubMed

Stefánsson, Einar; Olafsdottir, Olof Birna; Einarsdottir, Anna Bryndis; Eliasdottir, Thorunn Scheving; Eysteinsson, Thor; Vehmeijer, Wouter; Vandewalle, Evelien; Bek, Toke; Hardarson, Sveinn Hakon

2017-05-01

Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimer's disease, a change in retinal oxygen metabolism has been discovered. Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

Autoimmune diseases and vaccinations.

PubMed

Vial, Thierry; Descotes, Jacques

2004-01-01

The potential association between vaccination and autoimmune diseases has been largely questioned in the past few years, but this assumption has mostly been based on case reports. The available evidence derived from several negative epidemiological studies is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. However, there are still uncertainties as to whether a susceptible subpopulation may be at a higher risk of developing an autoimmune disease without causing an overall increase in the disease incidence. Based on selected examples, this review highlights the difficulties in assessing this issue. We suggest that a potential link between vaccines and autoimmune diseases cannot be definitely ruled out and should be carefully explored during the development of new candidate vaccines. Copyright John Libbey Eurotext 2003.

Changing trends in the treatment of dry-eye disease.

PubMed

Dogru, Murat; Nakamura, Masatsugu; Shimazaki, Jun; Tsubota, Kazuo

2013-12-01

Dry eye is a visually disabling disease encountered in many countries with a wide variation of treatment practices all over the world. On that front, the 2007 Report of the International Dry Eye WorkShop (DEWS) reviewed the current knowledge on all aspects of dry-eye disease (DED), in an evidence-based manner, and outlined the trends and recommendations in the treatment of DED on the basis of disease severity. This review mainly focuses on treatments for DED based on severity as recommended in the DEWS report, particularly artificial eye drops, hyaluronate sodium eye drops, autologous serum, anti-inflammatory eye drops including cyclosporine and steroids, and mucin secretagogues. New dry-eye treatment modalities in current trials outlined on the clinicaltrial.gov site are also outlined. Further investigations into the mechanism of action of the new mucin and tear secretagogues which have been suggested to have anti-inflammatory properties will enrich our understanding in relation to relevant ocular surface responses after treatment with these new agents.

Moderate Psoriasis: A Proposed Definition.

PubMed

Llamas-Velasco, M; de la Cueva, P; Notario, J; Martínez-Pilar, L; Martorell, A; Moreno-Ramírez, D

2017-12-01

The Psoriasis Area Severity Index (PASI) is the most widely used scale for assessing the severity of psoriasis and for therapeutic decision making. On the basis of the PASI score, patients have been stratified into 2 groups: mild disease and moderate-to-severe disease. To draft a proposal for the definition and characterization of moderate psoriasis based on PASI and Dermatology Life Quality Index (DLQI) scores. A group of 6 dermatologists with experience in the treatment of psoriasis undertook a critical review of the literature and a discussion of cases to draft a proposal. In order of priority, PASI, DLQI, and body surface area (BSA) are the parameters to be used in daily practice to classify psoriasis as mild, moderate, or severe. Severity should be assessed on the basis of a combined evaluation and interpretation of the PASI and DLQI. And 3, PASI and DLQI should carry equal weight in the determination of disease severity. On this basis, psoriasis severity was defined using the following criteria: mild, PASI<7 and DLQI<7; moderate, PASI=7-15 and DLQI=5-15 (classified as severe when difficult-to-treat sites are affected or when there is a significant psychosocial impact); severe, PASI >15, independently of the DLQI score. A more precise classification of psoriasis according to disease severity will improve the risk-benefit assessment essential to therapeutic decision making in these patients. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

First report of Armillaria root disease caused by Armillaria tabescens on Araucaria araucana in Veracruz, Mexico

Treesearch

M.-S. Kim; N. B. Klopfenstein; J. W. Hanna; P. Cannon; R. Medel; A. Lopez

2010-01-01

In September 2007, bark samples were collected from the root collar of a single Araucaria araucana tree that had recently died and was suspected of being killed by Armillaria root disease. Disease symptoms and signs included a thinning crown and fruiting bodies at the tree base over a several-year period before tree death.

Single-dose live-attenuated vesicular stomatitis virus-based vaccine protects African green monkeys from Nipah virus disease.

PubMed

Prescott, Joseph; DeBuysscher, Blair L; Feldmann, Friederike; Gardner, Donald J; Haddock, Elaine; Martellaro, Cynthia; Scott, Dana; Feldmann, Heinz

2015-06-04

Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. It is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of Nipah virus disease. There are no approved countermeasures to combat infection and medical intervention is supportive. We recently generated a recombinant replication-competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus glycoprotein as an antigen and is highly efficacious in the hamster model of Nipah virus disease. Herein, we show that this vaccine protects African green monkeys, a well-characterized model of Nipah virus disease, from disease one month after a single intramuscular administration of the vaccine. Vaccination resulted in a rapid and strong virus-specific immune response which inhibited virus shedding and replication. This vaccine platform provides a rapid means to afford protection from Nipah virus in an outbreak situation. Published by Elsevier Ltd.

Single-dose Live-attenuated Vesicular Stomatitis Virus-based Vaccine Protects African Green Monkeys from Nipah Virus Disease

PubMed Central

Prescott, Joseph; DeBuysscher, Blair L.; Feldmann, Friederike; Gardner, Donald J.; Haddock, Elaine; Martellaro, Cynthia; Scott, Dana; Feldmann, Heinz

2015-01-01

Nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. It is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in Bangladesh or India. Outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of Nipah virus disease. There are no approved countermeasures to combat infection and medical intervention is supportive. We recently generated a recombinant replication-competent vesicular stomatitis virus-based vaccine that encodes a Nipah virus glycoprotein as an antigen and is highly efficacious in the hamster model of Nipah virus disease. Herein, we show that this vaccine protects African green monkeys, a well-characterized model of Nipah virus disease, from disease one month after a single intramuscular administration of the vaccine. Vaccination resulted in a rapid and strong virus-specific immune response which inhibited virus shedding and replication. This vaccine platform provides a rapid means to afford protection from Nipah virus in an outbreak situation. PMID:25865472

Role of Curcumin in Disease Prevention and Treatment.

PubMed

Rahmani, Arshad Husain; Alsahli, Mohammed A; Aly, Salah M; Khan, Masood A; Aldebasi, Yousef H

2018-01-01

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases.

Role of Curcumin in Disease Prevention and Treatment

PubMed Central

Rahmani, Arshad Husain; Alsahli, Mohammed A.; Aly, Salah M.; Khan, Masood A.; Aldebasi, Yousef H.

2018-01-01

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases. PMID:29629341

T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

PubMed Central

Terajima, Masanori; Ennis, Francis A.

2011-01-01

We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions) and protection (vaccine design) which may need to take into account viral factors and the influence of HLA on T cell responses. PMID:21994770

T cells and pathogenesis of hantavirus cardiopulmonary syndrome and hemorrhagic fever with renal syndrome.

PubMed

Terajima, Masanori; Ennis, Francis A

2011-07-01

We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions) and protection (vaccine design) which may need to take into account viral factors and the influence of HLA on T cell responses.

Homeopathic Prevention and Management of Epidemic Diseases.

PubMed

Jacobs, Jennifer

2018-05-12

 Homeopathy has been used to treat epidemic diseases since the time of Hahnemann, who used Belladonna to treat scarlet fever. Since then, several approaches using homeopathy for epidemic diseases have been proposed, including individualization, combination remedies, genus epidemicus, and isopathy.  The homeopathic research literature was searched to find examples of each of these approaches and to evaluate which were effective.  There is good experimental evidence for each of these approaches. While individualization is the gold standard, it is impractical to use on a widespread basis. Combination remedies can be effective but must be based on the symptoms of a given epidemic in a specific location. Treatment with genus epidemicus can also be successful if based on data from many practitioners. Finally, isopathy shows promise and might be more readily accepted by mainstream medicine due to its similarity to vaccination.  Several different homeopathic methods can be used to treat epidemic diseases. The challenge for the future is to refine these approaches and to build on the knowledge base with additional rigorous trials. If and when conventional medicine runs out of options for treating epidemic diseases, homeopathy could be seen as an attractive alternative, but only if there is viable experimental evidence of its success. The Faculty of Homeopathy.

COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

PubMed

Kessler, Romain; Casan-Clara, Pere; Koehler, Dieter; Tognella, Silvia; Viejo, Jose Luis; Dal Negro, Roberto W; Díaz-Lobato, Salvador; Reissig, Karina; Rodríguez González-Moro, José Miguel; Devouassoux, Gilles; Chavaillon, Jean-Michel; Botrus, Pierre; Arnal, Jean-Michel; Ancochea, Julio; Bergeron-Lafaurie, Anne; De Abajo, Carlos; Randerath, Winfried J; Bastian, Andreas; Cornelissen, Christian G; Nilius, Georg; Texereau, Joëlle B; Bourbeau, Jean

2018-01-01

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients. Copyright ©ERS 2018.

Nairobi sheep disease virus/Ganjam virus.

PubMed

M D, Baron; B, Holzer

2015-08-01

Nairobi sheep disease virus (NSDV) is a tick-borne virus which causes a severe disease in sheep and goats, and has been responsible for several outbreaks of disease in East Africa. The virus is also found in the Indian subcontinent, where it is known as Ganjam virus. The virus only spreads through the feeding of competent infected ticks, and is therefore limited in its geographic distribution by the distribution of those ticks, Rhipicephalus appendiculata in Africa and Haemaphysalis intermedia in India. Animals bred in endemic areas do not normally develop disease, and the impact is therefore primarily on animals being moved for trade or breeding purposes. The disease caused by NSDV has similarities to several other ruminant diseases, and laboratory diagnosis is necessary for confirmation. There are published methods for diagnosis based on polymerase chain reaction, for virus growth in cell culture and for other simple diagnostic tests, though none has been commercialised. There is no established vaccine against NSDV, although cell-culture attenuated strains have been developed which show promise and could be put into field trials if it were deemed necessary. The virus is closely related to Crimean-Congo haemorrhagic fever virus, and studies on NSDV may therefore be useful in understanding this important human pathogen.

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.

The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

PubMed

Suruki, Robert Y; Daugherty, Jonas B; Boudiaf, Nada; Albers, Frank C

2017-04-27

Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

Medical treatment with thiamine, coenzyme Q, vitamins E and C, and carnitine improved obstructive sleep apnea in an adult case of Leigh disease.

PubMed

Mermigkis, Charalampos; Bouloukaki, Izolde; Mastorodemos, Vasileios; Plaitakis, Andreas; Alogdianakis, Vangelis; Siafakas, Nikolaos; Schiza, Sophia

2013-12-01

The multi-organ involvement of mitochondrial diseases means that patients are likely to be more vulnerable to sleep disturbances. We aimed to assess if early recognition and treatment of obstructive sleep apnea (OSA) in patients with Leigh disease may influence primary disease outcome. We describe a case of adult-onset Leigh disease presenting as severe brainstem encephalopathy of subacute onset. Based on the clinical symptoms that developed after the appearance of the neurological disease, an attended overnight polysomnography examination was performed. A marked clinical recovery was seen after administration of high doses of thiamine, coenzyme Q, L-carnitine, and vitamins C and E, combined with effective treatment with continuous positive airway pressure for the underlying severe obstructive sleep apnea (OSA). The latter condition was diagnosed on the basis of suggestive symptoms that appeared a few weeks before the establishment of the neurological disease. The improvement in the neurological disease (based on clinical and brain MRI features) with the appropriate medical treatment also resulted in a significant improvement in the OSA. Early recognition and treatment of sleep apnea may not only improve sleep and overall quality of life but also ameliorate the deleterious effects of nocturnal desaturations on the neurological features. This may be crucial for disease outcome when added to the generally advised pharmacological therapy.

Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

PubMed

von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

2013-01-01

Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p < 0.001). Atrial fibrillation, previous myocardial infarction and previous stroke were significantly more frequent in stroke patients; no differences in other baseline characteristics were found. Minor events are the most common in ischemic cerebrovascular disease, and may constitute a larger proportion than previously reported. TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

Potential coeliac disease markers and autoimmunity in olmesartan induced enteropathy: A population-based study.

PubMed

Esteve, Maria; Temiño, Rocío; Carrasco, Anna; Batista, Lissette; Del Val, Adolfo; Blé, Michel; Santaolaria, Santos; Molina-Infante, Javier; Soriano, Germán; Agudo, Sandra; Zabana, Yamile; Andújar, Xavier; Aceituno, Montserrat; Ribes, Josepa; Madridejos, Rosa; Fernández-Bañares, Fernando

2016-02-01

(1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. Crude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. Annual incidence rates (2011-2014) ranged from 0 to 22 cases per 10(4) treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+gammadelta+ intraepithelial lymphocytes and reduced CD3-). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Outpatient Chronic Obstructive Pulmonary Disease Management: Going for the GOLD.

PubMed

Bellinger, Christina R; Peters, Stephen P

2015-01-01

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States with a burden of $50 billion in direct health care costs. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines airflow obstruction as spirometry where the ratio of forced expiratory volume in the first second to forced vital capacity after bronchodilation is less than 0.70. The guidelines also provided graded recommendations on current therapy for COPD. Treatment can be guided based on severity of disease and severity of symptoms. We review the GOLD guidelines to provide an overview of treatment modalities aimed at improving lung function, reducing hospitalization, and reducing mortality. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes

USDA-ARS?s Scientific Manuscript database

The discovery of new drugs against microbial diseases is imperative to human and animal health. In this study, we synthesized a novel set of iron-based compounds and tested them against three widespread microbial diseases –tuberculosis, malaria, and trichomoniasis. Our results identified several lea...

Measurement of COPD Severity Using a Survey-Based Score

PubMed Central

Omachi, Theodore A.; Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Blanc, Paul D.

2010-01-01

Background: A comprehensive survey-based COPD severity score has usefulness for epidemiologic and health outcomes research. We previously developed and validated the survey-based COPD Severity Score without using lung function or other physiologic measurements. In this study, we aimed to further validate the severity score in a different COPD cohort and using a combination of patient-reported and objective physiologic measurements. Methods: Using data from the Function, Living, Outcomes, and Work cohort study of COPD, we evaluated the concurrent and predictive validity of the COPD Severity Score among 1,202 subjects. The survey instrument is a 35-point score based on symptoms, medication and oxygen use, and prior hospitalization or intubation for COPD. Subjects were systemically assessed using structured telephone survey, spirometry, and 6-min walk testing. Results: We found evidence to support concurrent validity of the score. Higher COPD Severity Score values were associated with poorer FEV1 (r = −0.38), FEV1% predicted (r = −0.40), Body mass, Obstruction, Dyspnea, Exercise Index (r = 0.57), and distance walked in 6 min (r = −0.43) (P < .0001 in all cases). Greater COPD severity was also related to poorer generic physical health status (r = −0.49) and disease-specific health-related quality of life (r = 0.57) (P < .0001). The score also demonstrated predictive validity. It was also associated with a greater prospective risk of acute exacerbation of COPD defined as ED visits (hazard ratio [HR], 1.31; 95% CI, 1.24-1.39), hospitalizations (HR, 1.59; 95% CI, 1.44-1.75), and either measure of hospital-based care for COPD (HR, 1.34; 95% CI, 1.26-1.41) (P < .0001 in all cases). Conclusion: The COPD Severity Score is a valid survey-based measure of disease-specific severity, both in terms of concurrent and predictive validity. The score is a psychometrically sound instrument for use in epidemiologic and outcomes research in COPD. PMID:20040611

Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition

PubMed Central

Hughes, L.; Ghosh, B. C. P.; Eckstein, D.; Williams-Gray, C. H.; Fallon, S.; Barker, R. A.; Owen, A. M.

2008-01-01

Cognitive deficits are very common in Parkinson's disease particularly for ‘executive functions’ associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinson's disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative ‘on’ and ‘off’ states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1–4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico–striato–thalamo–cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease. PMID:18577547

Celiac disease symptoms in a female collegiate tennis player: a case report.

PubMed

Leone, James E; Gray, Kimberly A; Massie, John E; Rossi, Jennifer M

2005-01-01

To present the case of a collegiate tennis player with celiac disease symptoms. Celiac disease is a common intestinal disorder that is often confused with other conditions. It causes severe intestinal damage manifested by several uncomfortable signs and symptoms. Failure by the sports medicine staff to recognize symptoms consistent with celiac disease and treat them appropriately can have deleterious consequences for the athlete. Irritable bowel syndrome, Crohn disease, Addison disease, lupus erythematosus, juvenile rheumatoid arthritis, lactose intolerance, herpes zoster, psychogenic disorder (depression), fibromyalgia, complex regional pain syndrome, hyperthyroidism, anemia, type I diabetes. The athlete underwent a series of blood and allergen tests to confirm or refute a diagnosis of celiac disease. When celiac disease was suspected, dietary modifications were made to eliminate all wheat-based and gluten-based products from the athlete's diet. The athlete was able to fully compete in a competitive National Collegiate Athletic Association Division I tennis program while experiencing the debilitating effects associated with celiac disease. The immediacy of symptom onset was notable because the athlete had no history of similar complaints. Celiac disease is a potentially life-threatening condition that affects more people than reported. A properly educated sports medicine staff can help to identify symptoms consistent with celiac disease early, so damage to the intestine is minimized. Prompt recognition and appropriate management allow the athlete to adjust the diet accordingly, compete at a high-caliber level, and enjoy a healthier quality of life.

Vaccines and immunization strategies for dengue prevention

PubMed Central

Liu, Yang; Liu, Jianying; Cheng, Gong

2016-01-01

Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults.

PubMed

Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

2016-01-08

Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.

Respiratory reviews in asthma 2013.

PubMed

Kim, Tae-Hyung

2014-03-01

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults

PubMed Central

Chen, Yu-ming; Liu, Yan; Zhou, Rui-fen; Chen, Xiao-ling; Wang, Cheng; Tan, Xu-ying; Wang, Li-jun; Zheng, Rui-dan; Zhang, Hong-wei; Ling, Wen-hua; Zhu, Hui-lian

2016-01-01

Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18–60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants. PMID:26743949

Recombinant allergy vaccines based on allergen-derived B cell epitopes.

PubMed

Valenta, Rudolf; Campana, Raffaela; Niederberger, Verena

2017-09-01

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensitivity disease. It affects more than 25% of the population. In IgE-sensitized subjects, allergen encounter can causes a variety of symptoms ranging from hayfever (allergic rhinoconjunctivitis) to asthma, skin inflammation, food allergy and severe life-threatening anaphylactic shock. Allergen-specific immunotherapy (AIT) is based on vaccination with the disease-causing allergens. AIT is an extremely effective, causative and disease-modifying treatment. However, administration of natural allergens can cause severe side effects and the quality of natural allergen extracts limits its application. Research in the field of molecular allergen characterization has allowed deciphering the molecular structures of the disease-causing allergens and it has become possible to engineer novel molecular allergy vaccines which precisely target the mechanisms of the allergic immune response and even appear suitable for prophylactic allergy vaccination. Here we discuss recombinant allergy vaccines which are based on allergen-derived B cell epitopes regarding their molecular and immunological properties and review the results obtained in clinical studies with this new type of allergy vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Health care priority setting in Norway a multicriteria decision analysis

PubMed Central

2012-01-01

Background Priority setting in population health is increasingly based on explicitly formulated values. The Patients Rights Act of the Norwegian tax-based health service guaranties all citizens health care in case of a severe illness, a proven health benefit, and proportionality between need and treatment. This study compares the values of the country's health policy makers with these three official principles. Methods In total 34 policy makers participated in a discrete choice experiment, weighting the relative value of six policy criteria. We used multi-variate logistic regression with selection as dependent valuable to derive odds ratios for each criterion. Next, we constructed a composite league table - based on the sum score for the probability of selection - to rank potential interventions in five major disease areas. Results The group considered cost effectiveness, large individual benefits and severity of disease as the most important criteria in decision making. Priority interventions are those related to cardiovascular diseases and respiratory diseases. Less attractive interventions rank those related to mental health. Conclusions Norwegian policy makers' values are in agreement with principles formulated in national health laws. Multi-criteria decision approaches may provide a tool to support explicit allocation decisions. PMID:22335815

Health care priority setting in Norway a multicriteria decision analysis.

PubMed

Defechereux, Thierry; Paolucci, Francesco; Mirelman, Andrew; Youngkong, Sitaporn; Botten, Grete; Hagen, Terje P; Niessen, Louis W

2012-02-15

Priority setting in population health is increasingly based on explicitly formulated values. The Patients Rights Act of the Norwegian tax-based health service guaranties all citizens health care in case of a severe illness, a proven health benefit, and proportionality between need and treatment. This study compares the values of the country's health policy makers with these three official principles. In total 34 policy makers participated in a discrete choice experiment, weighting the relative value of six policy criteria. We used multi-variate logistic regression with selection as dependent valuable to derive odds ratios for each criterion. Next, we constructed a composite league table - based on the sum score for the probability of selection - to rank potential interventions in five major disease areas. The group considered cost effectiveness, large individual benefits and severity of disease as the most important criteria in decision making. Priority interventions are those related to cardiovascular diseases and respiratory diseases. Less attractive interventions rank those related to mental health. Norwegian policy makers' values are in agreement with principles formulated in national health laws. Multi-criteria decision approaches may provide a tool to support explicit allocation decisions.

Nanotechnology based approaches for detection and delivery of microRNA in healthcare and crop protection.

PubMed

Chaudhary, Vrantika; Jangra, Sumit; Yadav, Neelam R

2018-04-13

Nanobiotechnology has the potential to revolutionize diverse sectors including medicine, agriculture, food, textile and pharmaceuticals. Disease diagnostics, therapeutics and crop protection strategies are fast emerging using nanomaterials preferably nanobiomaterials. It has potential for development of novel nanobiomolecules which offer several advantages over conventional treatment methods. RNA nanoparticles with many unique features are promising candidates in disease treatment. The miRNAs are involved in many biochemical and developmental pathways and their regulation in plants and animals. These appear to be a powerful tool for controlling various pathological diseases in human, plants and animals, however there are challenges associated with miRNA based nanotechnology. Several advancements made in the field of miRNA therapeutics make it an attractive approach, but a lot more has to be explored in nanotechnology assisted miRNA therapy. The miRNA based technologies can be employed for detection and combating crop diseases as well. Despite these potential advantages, nanobiotechnology applications in the agricultural sector are still in its infancy and have not yet made its mark in comparison with healthcare sector. The review provides a platform to discuss nature, role and use of miRNAs in nanobiotechnology applications.

Evaluation of Oil-Palm Fungal Disease Infestation with Canopy Hyperspectral Reflectance Data

PubMed Central

Lelong, Camille C. D.; Roger, Jean-Michel; Brégand, Simon; Dubertret, Fabrice; Lanore, Mathieu; Sitorus, Nurul A.; Raharjo, Doni A.; Caliman, Jean-Pierre

2010-01-01

Fungal disease detection in perennial crops is a major issue in estate management and production. However, nowadays such diagnostics are long and difficult when only made from visual symptom observation, and very expensive and damaging when based on root or stem tissue chemical analysis. As an alternative, we propose in this study to evaluate the potential of hyperspectral reflectance data to help detecting the disease efficiently without destruction of tissues. This study focuses on the calibration of a statistical model of discrimination between several stages of Ganoderma attack on oil palm trees, based on field hyperspectral measurements at tree scale. Field protocol and measurements are first described. Then, combinations of pre-processing, partial least square regression and linear discriminant analysis are tested on about hundred samples to prove the efficiency of canopy reflectance in providing information about the plant sanitary status. A robust algorithm is thus derived, allowing classifying oil-palm in a 4-level typology, based on disease severity from healthy to critically sick stages, with a global performance close to 94%. Moreover, this model discriminates sick from healthy trees with a confidence level of almost 98%. Applications and further improvements of this experiment are finally discussed. PMID:22315565

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

Finger taps and constipation are closely related to symptoms of overactive bladder in male patients with Parkinson's disease.

PubMed

Tsujimura, Akira; Yamamoto, Yoichi; Sakoda, Saburo; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Yoshioka, Iwao; Kiuchi, Hiroshi; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio

2014-01-01

To assess which motor and non-motor symptoms are closely related to overactive bladder severity in male patients with Parkinson's disease. A total of 160 male patients (mean age 71.4 ± 8.2 years) diagnosed with Parkinson's disease were included in the present study at Osaka University and affiliated hospitals. The severity of Parkinson's disease was classified as stage 3, 4 or 5 based on the Hoehn and Yahr staging system. Disease duration was 8.9 ± 5.1 years. Age, seven items from the Unified Parkinson's Disease Rating Scale motor section part III and three non-motor symptoms were assessed by multivariate analysis for their impact on the overactive bladder symptom score, a specific questionnaire for overactive bladder. Overactive bladder symptom score was significantly higher in the group with severe motor symptoms related to finger taps and gait than in the group with mild motor symptoms related to these two factors. Furthermore, overactive bladder symptom score of patients with erectile dysfunction and constipation was significantly higher than that in patients without these symptoms. Multivariate analysis identified only finger taps and constipation as factors independently associated with overactive bladder symptom score. Although a study on a larger scale is required to further assess the association of Parkinson's disease symptoms with overactive bladder symptom score, information on finger taps and severity of constipation should be obtained when assessing urological patients with Parkinson's disease. © 2013 The Japanese Urological Association.

Impact of a group-based model of disease management for headache.

PubMed

Maizels, Morris; Saenz, Valerie; Wirjo, Jonathan

2003-06-01

To assess the impact of a group-based model of disease management for patients with headache. Despite advances in the acute and preventive treatment of migraine, many patients with headache remain misdiagnosed and undertreated. Models of care that incorporate principles of disease management may improve headache care. This was a prospective, open-label, observational study. Patients with headache were referred by physicians or identified from emergency department records. Patients attended a group session led by a registered nurse practitioner, and later had follow-up consultation. Charts and computer records were reviewed to document triptan costs and headache-related visits for 6 months before and after the intervention. Changes in headache frequency and severity were assessed. Triptan costs for 264 patients and chart review for 250 were available. Six-month triptan costs increased $5423 US dollars(19%), headache-related visits were reduced by 32%, and headache-related emergency department visits were reduced by 49%. Severe headache frequency was reduced in 62 (86%) of 72 patients who initially had severe headaches more than 2 days per week. Patients identified by emergency department screening accounted for 21% of the study group, 31% of the baseline triptan costs, and 46% of the baseline visits. For the entire study group, reduced visits yielded a net savings of $18,757 US dollars despite increased triptan costs. Implementation of this group-based model produced a reduction in emergency department and clinic visits, significant clinical improvement, a small increase in pharmacy costs, and overall cost reduction. The greatest improvement in each outcome measure was seen in patients most severely afflicted at baseline. Our results suggest that the principles of disease management may be applied effectively to a headache population, with a positive financial impact on a managed care organization.

Predictors of Hospitalized Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease.

PubMed

Santibáñez, Miguel; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; García-Rivero, Juan Luis

2016-01-01

Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs-particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1-4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53-12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41-17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality.

Performance of International Classification of Diseases-based injury severity measures used to predict in-hospital mortality: A systematic review and meta-analysis.

PubMed

Gagné, Mathieu; Moore, Lynne; Beaudoin, Claudia; Batomen Kuimi, Brice Lionel; Sirois, Marie-Josée

2016-03-01

The International Classification of Diseases (ICD) is the main classification system used for population-based injury surveillance activities but does not contain information on injury severity. ICD-based injury severity measures can be empirically derived or mapped, but no single approach has been formally recommended. This study aimed to compare the performance of ICD-based injury severity measures to predict in-hospital mortality among injury-related admissions. A systematic review and a meta-analysis were conducted. MEDLINE, EMBASE, and Global Health databases were searched from their inception through September 2014. Observational studies that assessed the performance of ICD-based injury severity measures to predict in-hospital mortality and reported discriminative ability using the area under a receiver operating characteristic curve (AUC) were included. Metrics of model performance were extracted. Pooled AUC were estimated under random-effects models. Twenty-two eligible studies reported 72 assessments of discrimination on ICD-based injury severity measures. Reported AUC ranged from 0.681 to 0.958. Of the 72 assessments, 46 showed excellent (0.80 ≤ AUC < 0.90) and 6 outstanding (AUC ≥ 0.90) discriminative ability. Pooled AUC for ICD-based Injury Severity Score (ICISS) based on the product of traditional survival proportions was significantly higher than measures based on ICD mapped to Abbreviated Injury Scale (AIS) scores (0.863 vs. 0.825 for ICDMAP-ISS [p = 0.005] and ICDMAP-NISS [p = 0.016]). Similar results were observed when studies were stratified by the type of data used (trauma registry or hospital discharge) or the provenance of survival proportions (internally or externally derived). However, among studies published after 2003 the Trauma Mortality Prediction Model based on ICD-9 codes (TMPM-9) demonstrated superior discriminative ability than ICISS using the product of traditional survival proportions (0.850 vs. 0.802, p = 0.002). Models generally showed poor calibration. ICISS using the product of traditional survival proportions and TMPM-9 predict mortality more accurately than those mapped to AIS codes and should be preferred for describing injury severity when ICD is used to record injury diagnoses. Systematic review and meta-analysis, level III.

Effect of a Health Belief Model-based nursing intervention on Chinese patients with moderate to severe chronic obstructive pulmonary disease: a randomised controlled trial.

PubMed

Wang, Ying; Zang, Xiao-Ying; Bai, Jinbing; Liu, Su-Yan; Zhao, Yue; Zhang, Qing

2014-05-01

To test the effect of a Health Belief Model-based nursing intervention on healthcare outcomes in Chinese patients with moderate to severe COPD. The Health Belief Model (HBM) has been internationally validated in a variety of chronic conditions. However, nursing intervention based on the HBM is less explored in Chinese patients with COPD. A randomised controlled trial. Enrolled patients were randomly assigned to the intervention and control groups. Patients in the intervention group received a 20- to 30-minute HBM-based nursing intervention every 2 days during the hospitalisation period after disease conditions were stable, with additional follow-ups after discharge. Patients in the control group received routine nursing care. Patients had significantly increased scores of health belief and self-efficacy after receiving the HBM-based nursing intervention. After receiving the 3-month follow-up, patients in the intervention group had significantly higher mean total scores in the Health Belief Scale and the COPD Self-Efficacy Scale, as well as in all the subscales, than those in the control group except the perceived disease seriousness. Results showed that the value of FEV1 /FVC ratio had a significant difference between study groups before and after the intervention. Results also indicated that mean scores of the Dyspnea Scale, 6-minute walking distance and ADL were significantly different between the groups and between the study time-points. Among patients with moderate to severe COPD, nursing intervention based on the HBM can enhance their health belief and self-efficacy towards the disease management, decrease dyspnoea and improve exercise tolerance and ADL. Nurses can use the HBM-based intervention to enhance patients' health belief and self-efficacy towards the management of COPD, and subsequently benefit healthcare outcomes. © 2013 John Wiley & Sons Ltd.

Effect of quality chronic disease management for alcohol and drug dependence on addiction outcomes.

PubMed

Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

2012-12-01

We examined the effect of the quality of primary care-based chronic disease management (CDM) for alcohol and/or other drug (AOD) dependence on addiction outcomes. We assessed quality using (1) a visit frequency based measure and (2) a self-reported assessment measuring alignment with the chronic care model. The visit frequency based measure had no significant association with addiction outcomes. The self-reported measure of care-when care was at a CDM clinic-was associated with lower drug addiction severity. The self-reported assessment of care from any healthcare source (CDM clinic or elsewhere) was associated with lower alcohol addiction severity and abstinence. These findings suggest that high quality CDM for AOD dependence may improve addiction outcomes. Quality measures based upon alignment with the chronic care model may better capture features of effective CDM care than a visit frequency measure. Copyright © 2012 Elsevier Inc. All rights reserved.

POMICS: A Simulation Disease Model for Timing Fungicide Applications in Management of Powdery Mildew of Cucurbits.

PubMed

Sapak, Z; Salam, M U; Minchinton, E J; MacManus, G P V; Joyce, D C; Galea, V J

2017-09-01

A weather-based simulation model, called Powdery Mildew of Cucurbits Simulation (POMICS), was constructed to predict fungicide application scheduling to manage powdery mildew of cucurbits. The model was developed on the principle that conditions favorable for Podosphaera xanthii, a causal pathogen of this crop disease, generate a number of infection cycles in a single growing season. The model consists of two components that (i) simulate the disease progression of P. xanthii in secondary infection cycles under natural conditions and (ii) predict the disease severity with application of fungicides at any recurrent disease cycles. The underlying environmental factors associated with P. xanthii infection were quantified from laboratory and field studies, and also gathered from literature. The performance of the POMICS model when validated with two datasets of uncontrolled natural infection was good (the mean difference between simulated and observed disease severity on a scale of 0 to 5 was 0.02 and 0.05). In simulations, POMICS was able to predict high- and low-risk disease alerts. Furthermore, the predicted disease severity was responsive to the number of fungicide applications. Such responsiveness indicates that the model has the potential to be used as a tool to guide the scheduling of judicious fungicide applications.

Association Between Severity of Obstructive Sleep Apnea and Blood Markers of Liver Injury.

PubMed

Trzepizur, Wojciech; Boursier, Jérôme; Mansour, Yasmina; Le Vaillant, Marc; Chollet, Sylvaine; Pigeanne, Thierry; Bizieux-Thaminy, Acya; Humeau, Marie-Pierre; Alizon, Claire; Goupil, François; Meslier, Nicole; Priou, Pascaline; Calès, Paul; Gagnadoux, Frédéric

2016-11-01

Obstructive sleep apnea (OSA) may contribute to the development of nonalcoholic fatty liver disease. We performed a multisite cross-sectional study to evaluate the association between the severity of OSA and blood markers of liver steatosis (using the hepatic steatosis index), cytolysis (based on alanine aminotransferase activity), and significant liver fibrosis (based on the FibroMeter [Echosens] nonalcoholic fatty liver disease score) in 1285 patients with suspected OSA in France. After adjusting for confounders including central obesity, the risk of liver steatosis increased with the severity of OSA (P for trend < .0001) and sleep-related hypoxemia (P for trend < .0003 for mean oxygen saturation). Decreasing mean oxygen saturation during sleep also was associated independently with a higher risk of liver cytolysis (P for trend < .0048). Severe OSA conferred an approximate 2.5-fold increase in risk for significant liver fibrosis compared with patients without OSA, but the association between OSA severity and liver fibrosis was not maintained after adjusting for confounders. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

When Are High-Tech Communicators Effective in Parkinson's Disease?

ERIC Educational Resources Information Center

Ferriero, Giorgio; Caligari, Marco; Ronconi, Gianpaolo; Franchignoni, Franco

2012-01-01

This report describes a 63-year-old woman with Parkinson's disease showing loss of intelligibility of speech and severely impaired handwriting, despite undergoing physical and speech therapies. As the patient had sufficient residual motor abilities and adequate cognitive function and motivation, a computer-based communication aid with a software…

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

Correlations of sleep disorders with severity of obstructive airway disease in mustard gas-injured patients.

PubMed

Vahedi, Ensieh; Taheri, Saeed; Alaedini, Farshid; Poursaleh, Zohreh; Ameli, Javad; Ghanei, Mostafa

2012-06-01

Mustard gas has serious adverse effects on several organs and functions in humans. In this study, we analyzed potential correlations between obstructive airway disease and sleep disorders in Iranian mustard gas-injured patients. We enrolled 30 male mustard gas-injured veterans and civilians from the Chemical Warfare Exposure Clinic at Baqiyatallah Hospital, Tehran. All the subjects underwent comprehensive polysomnographic and spirometric evaluations for diagnosis of sleep disorders. Patients were categorized into three groups according to the severity of their obstructive airway disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: group 1 (GOLD I and II), group 2 (GOLD III), and group 3 (GOLD IV). Patients with less severe obstructive airway disease had significantly higher rate of hypopnea (p = 0.05) and AHI (p = 0.05). The number of REM events was significantly higher in patients with less severe airway disease (p = 0.028). Stage 1 sleep among patients with higher FEV1 significantly constituted a higher proportion of sleep, and stage 4 sleep was significantly longer in patients with higher DLCO (p = 0.043, both). We found that sleep parameters in SM-exposed patients have some relations with spirometric parameters. Future studies with large patient populations are needed for confirmation of our results, and therapeutic interventions are needed to evaluate endeavors we can do to enhance health and quality of life in our mustard gas-injured population.

A Novel Image Recuperation Approach for Diagnosing and Ranking Retinopathy Disease Level Using Diabetic Fundus Image

PubMed Central

2015-01-01

Retinal fundus images are widely used in diagnosing and providing treatment for several eye diseases. Prior works using retinal fundus images detected the presence of exudation with the aid of publicly available dataset using extensive segmentation process. Though it was proved to be computationally efficient, it failed to create a diabetic retinopathy feature selection system for transparently diagnosing the disease state. Also the diagnosis of diseases did not employ machine learning methods to categorize candidate fundus images into true positive and true negative ratio. Several candidate fundus images did not include more detailed feature selection technique for diabetic retinopathy. To apply machine learning methods and classify the candidate fundus images on the basis of sliding window a method called, Diabetic Fundus Image Recuperation (DFIR) is designed in this paper. The initial phase of DFIR method select the feature of optic cup in digital retinal fundus images based on Sliding Window Approach. With this, the disease state for diabetic retinopathy is assessed. The feature selection in DFIR method uses collection of sliding windows to obtain the features based on the histogram value. The histogram based feature selection with the aid of Group Sparsity Non-overlapping function provides more detailed information of features. Using Support Vector Model in the second phase, the DFIR method based on Spiral Basis Function effectively ranks the diabetic retinopathy diseases. The ranking of disease level for each candidate set provides a much promising result for developing practically automated diabetic retinopathy diagnosis system. Experimental work on digital fundus images using the DFIR method performs research on the factors such as sensitivity, specificity rate, ranking efficiency and feature selection time. PMID:25974230

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.

Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

PubMed Central

Johansen, Morten Bo; Izarzugaza, Jose M. G.; Brunak, Søren; Petersen, Thomas Nordahl; Gupta, Ramneek

2013-01-01

We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP PMID:23935863

Prevalence and Risk Factors of Subclinical Thyroid Disease

PubMed Central

Kim, Ye An

2014-01-01

Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism. PMID:24741450

The effect of a Web-based education programme (WBEP) on disease severity, quality of life and mothers' self-efficacy in children with atopic dermatitis.

PubMed

Son, Hae Kyoung; Lim, Jiyoung

2014-10-01

To develop and evaluate the effects of a web-based education programme in early childhood for children with atopic dermatitis. The prevalence rate of atopic dermatitis is highest in early childhood. A holistic approach is urgently needed for young children with respect to disease severity, quality of life and management, particularly parental knowledge about atopic dermatitis and adherence to treatment. A quasi-experimental study design was used. A total of 40 mother-child dyads participated in the study from 1 July-30 November 2011 in Korea. All children were under 3 years of age. The programme was based on the Network-Based Instructional System Design model, which consists of five phases: analysis, design, development, implementation and evaluation. The experimental group participated in the programme for 2 weeks. Participants took part in a learning session during the first week and then conducted the practice session at home during the second week. Participant knowledge and compliance were evaluated through online quizzes and self-checklists. Statistical analyses (chi-square test and t-test) were performed using the Statistical Analysis System, Version 9.13. There was a significant improvement in disease severity, quality of life and mothers' self-efficacy in the experimental group; thus, the web-based education programme was effective. The web-based education programme as an advanced intervention may be useful in providing basic data for future atopic dermatitis-related studies. Moreover, the programme may serve as a nursing educational intervention tool for clinical nursing practices. © 2014 John Wiley & Sons Ltd.

Management of dry eye disease.

PubMed

Lemp, Michael A

2008-04-01

The management of dry eye disease (DED) encompasses both pharmacologic and nonpharmacologic approaches, including avoidance of exacerbating factors, eyelid hygiene, tear supplementation, tear retention, tear stimulation, and anti-inflammatory agents. Artificial tears are the mainstay of DED therapy but, although they improve symptoms and objective findings, there is no evidence that they can resolve the underlying inflammation in DED. Topical corticosteroids are effective anti-inflammatory agents, but are not recommended for long-term use because of their adverse-effect profiles. Topical cyclosporine--currently the only pharmacologic treatment approved by the US Food and Drug Administration specifically for DED--is safe for long-term use and is disease-modifying rather than merely palliative. Treatment selection is guided primarily by DED severity. Recently published guidelines propose a severity classification based on clinical signs and symptoms, with treatment recommendations according to severity level.

A statistically derived index for classifying East Coast fever reactions in cattle challenged with Theileria parva under experimental conditions.

PubMed

Rowlands, G J; Musoke, A J; Morzaria, S P; Nagda, S M; Ballingall, K T; McKeever, D J

2000-04-01

A statistically derived disease reaction index based on parasitological, clinical and haematological measurements observed in 309 5 to 8-month-old Boran cattle following laboratory challenge with Theileria parva is described. Principal component analysis was applied to 13 measures including first appearance of schizonts, first appearance of piroplasms and first occurrence of pyrexia, together with the duration and severity of these symptoms, and white blood cell count. The first principal component, which was based on approximately equal contributions of the 13 variables, provided the definition for the disease reaction index, defined on a scale of 0-10. As well as providing a more objective measure of the severity of the reaction, the continuous nature of the index score enables more powerful statistical analysis of the data compared with that which has been previously possible through clinically derived categories of non-, mild, moderate and severe reactions.

Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells

PubMed Central

Maher, John

2012-01-01

Chimeric antigen receptor- (CAR-) based immunotherapy has been under development for almost 25 years, over which period it has progressed from a new but cumbersome technology to an emerging therapeutic modality for malignant disease. The approach involves the genetic engineering of fusion receptors (CARs) that couple the HLA-independent binding of cell surface target molecules to the delivery of a tailored activating signal to host immune cells. Engineered CARs are delivered most commonly to peripheral blood T cells using a range of vector systems, most commonly integrating viral vectors. Preclinical refinement of this approach has proceeded over several years to the point that clinical testing is now being undertaken at several centres, using increasingly sophisticated and therapeutically successful genetic payloads. This paper considers several aspects of the pre-clinical and clinical development of CAR-based immunotherapy and how this technology is acquiring an increasing niche in the treatment of both solid and haematological malignancies. PMID:23304553

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

PubMed

Knapp, Martin; King, Derek; Romeo, Renée; Adams, Jessica; Baldwin, Ashley; Ballard, Clive; Banerjee, Sube; Barber, Robert; Bentham, Peter; Brown, Richard G; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Johnson, Tony; Jones, Robert; Katona, Cornelius; Lindesay, James; Macharouthu, Ajay; McKeith, Ian; McShane, Rupert; O'Brien, John T; Phillips, Patrick P J; Sheehan, Bart; Howard, Robert

2017-12-01

Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Cost effectiveness of a targeted age-based West Nile virus vaccination program.

PubMed

Shankar, Manjunath B; Staples, J Erin; Meltzer, Martin I; Fischer, Marc

2017-05-25

West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease. We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years. There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p<0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected. Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios. Published by Elsevier Ltd.

The impact of social and psychological consequences of disease on judgments of disease severity: An experimental study.

PubMed

King, Nicholas B; Harper, Sam; Young, Meredith; Berry, Sarah C; Voigt, Kristin

2018-01-01

The Global Burden of Disease (GBD) project systematically assesses mortality, healthy life expectancy, and disability across 195 countries and territories, using the disability-adjusted life year (DALY). Disability weights in the DALY are based upon surveys that ask users to rate health states based on lay descriptions. We conducted an experimental study to examine whether the inclusion or removal of psychological, social, or familial implications from a health state description might affect individual judgments about disease severity, and thus relative disability weights. We designed a survey consisting of 36 paired descriptions in which information about plausible psychological, social, or familial implications of a health condition was either present or absent. Using a Web-based platform, we recruited 1,592 participants, who were assigned to one of two experimental groups, each of which were asked to assign a value to the health state description from 0 to 100 using a slider, with 0 as the "worst possible health" and 100 as the "best possible health." We tested five hypotheses: (1) the inclusion of psychological, social, or familial consequences in health state descriptions will reduce the average rating of a health state; (2) the effect will be stronger for diseases with lower disability weights (i.e., less severe diseases); (3) the effect will vary across the type of additional information added to the health state description; (4) the impact of adding information on familial consequences will be stronger for female than male; (5) the effect of additional consequences on ratings of health state descriptions will not differ by levels of completed education and age. On average, adding social, psychological, or familial consequences to the health state description lowered individual ratings of that description by 0.78 points. The impact of adding information had a stronger impact on ratings of the least severe conditions, reducing average ratings in this category by 1.67 points. Addition of information about child-rearing had the strongest impact, reducing average ratings by 2.09 points. We found little evidence that the effect of adding information on ratings of health descriptions varied by gender, education, or age. Including information about health states not directly related to major functional consequences or symptoms, particularly with respect to child-rearing and specifically for descriptions of less severe conditions, can lead to lower ratings of health. However, this impact was not consistent across all conditions or types of information, and was most pronounced for inclusion of information about child-rearing, and among the least severe conditions.

Concordance between patient and clinician assessment of dry eye severity and treatment response in Taiwan.

PubMed

Yeh, Po-Ting; Chien, Hsu-Chih; Ng, Kwong; Tseng, Sung-Huei; Chen, Wei-Li; Hou, Yu-Chih; Wang, I-Jong; Chu, Hsiao-Sung; Kao Yang, Yea-Huei; Hu, Fung-Rong

2015-05-01

Accurate diagnosis and early recognition of dry eye symptoms are important in the management of dry eye disease (DED). This study aimed to evaluate concordance between patient and clinician assessment of DED severity and treatment response. This cross-sectional study was conducted in 2 ophthalmology clinics in Taiwan. Clinicians assessed severity based on the Dry Eye Workshop severity grading (levels 1-4; where 4 = most severe), whereas patients completed the Ocular Surface Disease Index questionnaire. To evaluate the treatment response, patients completed the Subject Global Assessment scale, and clinicians independently assessed patients using the Clinical Global Impression scale. A total of 466 patients were included. Clinicians graded 88.3% of patients as level 1/2, 9.0% as level 3, and 2.7% as level 4 Dry Eye Workshop severity, whereas 44.9% of patients reported normal/mild symptoms, 17.1% with moderate severity, and 38.0% with severe DED. Patients were primarily treated with artificial tears. The clinician assessed 10.3% of patients as unchanged on disease severity after treatment and 88.0% as improved, whereas 49.2% of patients reported dry eye symptoms being almost the same after treatment and 34.6% reported improved symptoms. There was low agreement between clinician and patient assessments in terms of disease severity (rho = 0.17, P < 0.001) and treatment response (rho = 0.22, P < 0.001). There were marked differences in the degree of DED severity and treatment response between patient and clinician assessment. Clinicians may underestimate DED severity and persistence of dry eye symptoms after treatment with artificial tears.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942226.

Intracranial vessel wall imaging for evaluation of steno-occlusive diseases and intracranial aneurysms.

PubMed

Brinjikji, Waleed; Mossa-Basha, Mahmud; Huston, John; Rabinstein, Alejandro A; Lanzino, Giuseppe; Lehman, Vance T

2017-03-01

Cerebrovascular diseases have traditionally been classified, diagnosed and managed based on their luminal characteristics. However, over the past several years, several advancements in MRI techniques have ushered in high-resolution vessel wall imaging (HR-VWI), enabling evaluation of intracranial vessel wall pathology. These advancements now allow us to differentiate diseases which have a common angiographic appearance but vastly different natural histories (i.e. moyamoya versus atherosclerosis, reversible cerebral vasoconstriction syndrome versus vasculitis, stable versus unstable intracranial aneurysms). In this review, we detail the anatomical, histopathological and imaging characteristics of various intracranial steno-occlusive diseases and types of intracranial aneurysms and describe the role that HR-VWI can play in diagnosis, risk stratification and treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Childhood hospitalisation with infection and cardiovascular disease in early-mid adulthood: a longitudinal population-based study.

PubMed

Burgner, David P; Cooper, Matthew N; Moore, Hannah C; Stanley, Fiona J; Thompson, Peter L; de Klerk, Nicholas H; Carter, Kim W

2015-01-01

Pathogen-specific and overall infection burden may contribute to atherosclerosis and cardiovascular disease (CVD), but the effect of infection severity and timing is unknown. We investigated whether childhood infection-related hospitalisation (IRH, a marker of severity) was associated with subsequent adult CVD hospitalisation. Using longitudinal population-based statutorily-collected administrative health data from Western Australia (1970-2009), we identified adults hospitalised with CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) and matched them (10:1) to population controls. We used Cox regression to assess relationships between number and type of childhood IRH and adulthood CVD hospitalisation, adjusting for sex, age, Indigenous status, socioeconomic status, and birth weight. 631 subjects with CVD-related hospitalisation in adulthood (≥ 18 years) were matched with 6310 controls. One or more childhood (< 18 years) IRH was predictive of adult CVD-related hospitalisation (adjusted hazard ratio, 1.3; 95% CI 1.1-1.6; P < 0.001). The association showed a dose-response; ≥ 3 childhood IRH was associated with a 2.2 times increased risk of CVD-related hospitalisation in adulthood (adjusted hazard ratio, 2.2; 95% CI 1.7-2.9; P < 0.001). The association was observed across all clinical diagnostic groups of infection (upper respiratory tract infection, lower respiratory tract infection, infectious gastroenteritis, urinary tract infection, skin and soft tissue infection, and other viral infection), and individually with CVD diagnostic categories (ischaemic heart disease, ischaemic stroke and peripheral vascular disease). Severe childhood infection is associated with CVD hospitalisations in adulthood in a dose-dependent manner, independent of population-level risk factors.

A review of health utilities using the EQ-5D in studies of cardiovascular disease

PubMed Central

2010-01-01

Background The EQ-5D has been extensively used to assess patient utility in trials of new treatments within the cardiovascular field. The aims of this study were to review evidence of the validity and reliability of the EQ-5D, and to summarise utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cardiovascular disease. Methods A structured literature search was conducted using keywords related to cardiovascular disease and EQ-5D. Original research studies of patients with cardiovascular disease that reported EQ-5D results and its measurement properties were included. Results Of 147 identified papers, 66 met the selection criteria, with 10 studies reporting evidence on validity or reliability and 60 reporting EQ-5D responses (VAS or self-classification). Mean EQ-5D index-based scores ranged from 0.24 (SD 0.39) to 0.90 (SD 0.16), while VAS scores ranged from 37 (SD 21) to 89 (no SD reported). Stratification of EQ-5D index scores by disease severity revealed that scores decreased from a mean of 0.78 (SD 0.18) to 0.51 (SD 0.21) for mild to severe disease in heart failure patients and from 0.80 (SD 0.05) to 0.45 (SD 0.22) for mild to severe disease in angina patients. Conclusions The published evidence generally supports the validity and reliability of the EQ-5D as an outcome measure within the cardiovascular area. This review provides utility estimates across a range of cardiovascular subgroups and treatments that may be useful for future modelling of utilities and QALYs in economic evaluations within the cardiovascular area. PMID:20109189

Potential for Stem Cell-Based Periodontal Therapy

PubMed Central

Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C.; Intini, Giuseppe

2015-01-01

Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

[Involvement of mucous membranes in autoimmune bullous diseases].

PubMed

Günther, C

2016-10-01

Autoimmune bullous diseases are characterized by intraepidermal or subepidermal autoantibody deposition that leads to blisters and secondary erosion. Mucous membranes are frequently affected in pemphigus vulgaris and always involved in cicatricial and mucosal pemphigoid. Mucosal lesions are detected less frequently in patients with bullous pemphigoid or epidermolysis bullosa acquisita. The diagnosis of autoimmune bullous disorders is based on determination of the subtype of autoantibodies bound in the skin and the clinical picture. Treatment is based on immunosuppression related to the type of disease and severity of the mucosal symptoms. Ocular involvement in mucosal pemphigoid and pemphigus vulgaris requires systemic treatment.

Approaches to the Surveillance of Foodborne Disease: A Review of the Evidence.

PubMed

Ford, Laura; Miller, Megge; Cawthorne, Amy; Fearnley, Emily; Kirk, Martyn

2015-12-01

Foodborne disease surveillance aims to reduce the burden of illness due to contaminated food. There are several different types of surveillance systems, including event-based surveillance, indicator-based surveillance, and integrated food chain surveillance. These approaches are not mutually exclusive, have overlapping data sources, require distinct capacities and resources, and can be considered a hierarchy, with each level being more complex and resulting in a greater ability to detect and control foodborne disease. Event-based surveillance is generally the least resource-intensive system and makes use of informal data sources. Indicator-based surveillance is seen as traditional notifiable disease surveillance and consists of routinely collected data. Integrated food chain surveillance is viewed as the optimal practice for conducting continuous risk analysis for foodborne diseases, but also requires significant ongoing resources and greater multisectoral collaboration compared to the other systems. Each country must determine the most appropriate structure for their surveillance system for foodborne diseases based on their available resources. This review explores the evidence on the principles, minimum capabilities, and minimum requirements of each type of surveillance and discusses examples from a range of countries. This review forms the evidence base for the Strengthening the Surveillance and Response for Foodborne Diseases: A Practical Manual.

[State of the art diagnostic criteria of severe periodontitis].

PubMed

Ouyang, X Y

2017-02-09

Periodontitis could be categorized as mild, moderate, and severe according to the severity of the disease. This categorizing system could also be used together with other classification systems. The present article introduced the status about the case definition of severe periodontitis, including the standard of case definitions for surveillance of periodontitis reported by the Centers for Disease Control and Prevention (CDC) in partnership with the American Academy of Periodontology (AAP) and the consensus report on the definition of periodontitis case for use in risk factor research by Europe workshop. A consensus on the state of the art definition of severe periodontitis for use in clinical work was gained base on the expertise of Chinese Society of Periodontology, Chinese Association of Stomatology. The background of this consensus and the significance of the criteria for the case definition were discussed.

The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

PubMed Central

Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

2014-01-01

Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

[Researches on virology at the Tohoku University Research Center in the Philippines].

PubMed

Oshitani, Hitoshi; Saito, Mariko; Okamoto, Michiko; Tamaki, Raita; Kamigaki, Taro; Suzuki, Akira

2013-01-01

Tohoku University Graduate School of Medicine has established the Tohoku-RITM Collaborative Research Center on Emerging and Re-emerging Diseases at Research Institute for Tropical Medicine (RITM) in the Philippines in 2008. Our aim of the center is to conduct operational researches, which can contribute to control of infectious diseases in the Philippines. Therefore most of our researches in the Philippines are being conducted in the fields. Main research themes include severe acute respiratory infections in children, influenza disease burden study, molecular epidemiology of rabies, and viral etiology of acute diarrhea. The study on severe acute respiratory infections in children in Leyte Island has recruited hospitalized cases with severe pneumonia. We showed that enterovirus 68 was one of important causative agents in severe pneumonia cases. We also conducted other analyses including molecular epidemiology of respiratory syncytial virus (RSV) and pathogenesis of human rhinoviruses (HRV). Based on these studies, we initiated more comprehensive researches in the Philippines since 2010.

The severity of Minamata disease declined in 25 years: temporal profile of the neurological findings analyzed by multiple logistic regression model.

PubMed

Uchino, Makoto; Hirano, Teruyuki; Satoh, Hiroshi; Arimura, Kimiyoshi; Nakagawa, Masanori; Wakamiya, Jyunji

2005-01-01

Minamata disease (MD) was caused by ingestion of seafood from the methylmercury-contaminated areas. Although 50 years have passed since the discovery of MD, there have been only a few studies on the temporal profile of neurological findings in certified MD patients. Thus, we evaluated changes in neurological symptoms and signs of MD using discriminants by multiple logistic regression analysis. The severity of predictive index declined in 25 years in most of the patients. Only a few patients showed aggravation of neurological findings, which was due to complications such as spino-cerebellar degeneration. Patients with chronic MD aged over 45 years had several concomitant diseases so that their clinical pictures were complicated. It was difficult to differentiate chronic MD using statistically established discriminants based on sensory disturbance alone. In conclusion, the severity of MD declined in 25 years along with the modification by age-related concomitant disorders.

Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

PubMed

Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

2018-04-18

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

PubMed

Juillerat, Pascal; Pittet, Valérie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Wolters, Frank L; Stockbrügger, Reinhold W; Michetti, Pierre

2010-12-01

The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Deciphering the transcriptomic response of Fusarium verticillioides in relation to nitrogen availability and the development of sugarcane pokkah boeng disease

NASA Astrophysics Data System (ADS)

Lin, Zhenyue; Wang, Jihua; Bao, Yixue; Guo, Qiang; Powell, Charles A.; Xu, Shiqiang; Chen, Baoshan; Zhang, Muqing

2016-07-01

Pokkah boeng, caused by Fusarium verticillioides, is a serious disease in sugarcane industry. The disease severity is related to the sugarcane genotype as well as environmental considerations, such as nitrogen application. The impact of the nitrogen source (ammonium sulfate, urea, or sodium nitrate) on sugarcane pokkah boeng disease and its pathogen was investigated in planta and fungal growth and sporulation production was measured in vitro. The results showed that ammonium and nitrate were beneficial to fungal mycelium growth, cell densities, and sporulation, which enhanced the disease symptoms of sugarcane pokkah boeng compared to urea fertilization. A total of 1,779 transcripts out of 13,999 annotated genes identified from global transcriptomic analysis were differentially expressed in F. verticillioides CNO-1 grown in the different sources of nitrogen. These were found to be involved in nitrogen metabolism, transport, and assimilation. Many of these genes were also associated with pathogenicity based on the PHI-base database. Several transcription factors were found to be associated with specific biological processes related to nitrogen utilization. Our results further demonstrated that nitrogen availability might play an important role in disease development by increasing fungal cell growth as well as influencing the expression of genes required for successful pathogenesis.

Contribution of pertussis toxin to the pathogenesis of pertussis disease

PubMed Central

Carbonetti, Nicholas H.

2015-01-01

Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

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.

Cardiovascular disease in persons with depressive and anxiety disorders.

PubMed

Vogelzangs, Nicole; Seldenrijk, Adrie; Beekman, Aartjan T F; van Hout, Hein P J; de Jonge, Peter; Penninx, Brenda W J H

2010-09-01

Associations between depression, and possibly anxiety, with cardiovascular disease have been established in the general population and among heart patients. This study examined whether cardiovascular disease was more prevalent among a large cohort of depressed and/or anxious persons. In addition, the role of specific clinical characteristics of depressive and anxiety disorders in the association with cardiovascular disease was explored. Baseline data from the Netherlands Study of Depression and Anxiety were used, including persons with a current (i.e. past year) or remitted DSM-IV depressive or anxiety disorder (N=2315) and healthy controls (N=492). Additional clinical characteristics (subtype, duration, severity, and psychoactive medication) were assessed. Cardiovascular disease (stroke and coronary heart disease) was assessed using algorithms based on self-report and medication use. Persons with current anxiety disorders showed an about three-fold increased prevalence of coronary heart disease (OR anxiety only=2.70, 95%CI=1.31-5.56; OR comorbid anxiety/depression=3.54, 95%CI=1.79-6.98). No associations were found for persons with depressive disorders only or remitted disorders, nor for stroke. Severity of depressive and anxiety symptoms--but no other clinical characteristics--most strongly indicated increased prevalence of coronary heart disease. Cross-sectional design. Within this large psychopathology-based cohort study, prevalence of coronary heart disease was especially increased among persons with anxiety disorders. Increased prevalence of coronary heart disease among depressed persons was largely owing to comorbid anxiety. Anxiety-alone as well as comorbid to depressive disorders-as risk indicator of coronary heart disease deserves more attention in both research and clinical practice. 2010 Elsevier B.V. All rights reserved.

Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK.

PubMed

Rose, Tanith C; Adams, Natalie L; Barr, Benjamin; Hawker, Jeremy; O'Brien, Sarah J; Violato, Mara; Whitehead, Margaret; Taylor-Robinson, David C

2017-06-23

The burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or the extent to which they relate to disease severity. We performed a cross-sectional analysis using IID cases identified from a large population-based survey, to explore the association between socioeconomic status (SES) and symptom severity and sickness absence; and to assess the role of symptom severity on the relationship between SES and absence. Regression modelling was used to investigate these associations, whilst controlling for potential confounders such as age, sex and ethnicity. Among 1164 cases, those of lower SES versus high had twice the odds of experiencing severe symptoms (OR 2.2, 95%CI;1.66-2.87). Lower SES was associated with higher odds of sickness absence (OR 1.8, 95%CI;1.26-2.69), however this association was attenuated after adjusting for symptom severity (OR 1.4, 95%CI;0.92-2.07). In a large sample of IID cases, those of low SES versus high were more likely to report severe symptoms, and sickness absence; with greater severity largely explaining the higher absence. Public health interventions are needed to address the unequal consequences of IID identified.

[Obesity, a disease].

PubMed

Basdevant, Arnaud; Ciangura, Cécile

2010-01-01

Obesity has been considered as a disease by the World Health Organisation since 1997. It was previously considered a simple risk factor and a manifestation of consumer society. This recognition was based on several developments, including epidemiological data showing the worldwide spread of the disease; the increasing health expenditure due to the obesity-related increase in type 2 diabetes; and progress in pathophysiological concepts. Obesity is a chronic and progressive disease. Management approaches range from prevention to surgery, and must be adapted to the individual situation.

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.

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

PubMed

Cecchini, Jérôme; Tuffet, Samuel; Sonneville, Romain; Fartoukh, Muriel; Mayaux, Julien; Roux, Damien; Kouatchet, Achille; Boissier, Florence; Tchir, Martial; Thyrault, Martial; Maury, Eric; Jochmans, Sebastien; Mekontso Dessap, Armand; Brun-Buisson, Christian; de Prost, Nicolas

2017-05-01

Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. To evaluate the effect of antimicrobial strategy on ICU mortality. Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P  =   0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P  =   0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P  =   0.02]. Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study

PubMed Central

Ramos, Alexis; Sicilia, Beatriz; Vergara, Mercedes; Figuerola, Ariadna; Motos, Jaume; Sastre, Adoración; Villoria, Albert; Gomollón, Fernando

2015-01-01

Background and aims Data on the prevalence of work disability in patients with inflammatory bowel disease (IBD) are heterogeneous. As most studies have been performed in selected, often severe, IBD patients, the true prevalence of disability in the community remains controversial. The aim of this cross-sectional study was to evaluate the prevalence and severity of disability and its predictive factors in a community-based IBD population. Patients and methods Patients recorded in the community-based IBD register at the Hospital Universitario de Burgos were contacted. After informed consent they completed a set of questionnaires including demographic, clinical, disability and quality of life data. The statistical study was performed using SPSS 21. Results A total of 293 patients were included – 151 Crohn's disease (CD), 142 ulcerative colitis (UC), 137 female, mean age: 45 ± 11 years, mean time since diagnosis: 10.6 ± 11 years. Twelve patients (4.1%) had a work-disability pension. In addition, 93 (32%) of all patients had an officially recognized disability degree, which was generally moderate (n = 73, 25%) or severe (N = 16, 5%). Age, time since IBD diagnosis, CD, perianal disease, incontinence, active disease, the need for anti-TNF or psychological treatment, previous surgeries and the number of diagnostic tests and medical visits in the previous year were predictors of disability. Major predictors of qualifying for a disability pension were age, IBD activity, incontinence, need for biological drugs and ostomy. Conclusion Mild to moderate work disability is frequent in IBD. However, only a minority of patients develop severe disability qualifying them for a pension. PMID:26279841

The Bordetella bronchiseptica type III secretion system is required for persistence and disease severity but not transmission in swine

USDA-ARS?s Scientific Manuscript database

Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Most studies addressing virulence factors of B. bronchiseptica utilize isolates derived from hosts other than pigs in conjunction with rodent infection models. Based on previous in vivo mouse...

Control of Lophodermium needlecast disease in nurseries and Christmas tree plantations.

Treesearch

Thomas H. Nicholls; Darroll D. Skilling

1974-01-01

Recommendations are based upon studies initiated by the USDA Forest Service as a result of an outbreak of Lophodermium needlecast in several nurseries in the Lake States that spread to plantations throughout the United States due, in part, to shipment of diseased seedlings during the late 1960's and early 1970's.

Melmark New England

ERIC Educational Resources Information Center

Cancro, Lorraine

2009-01-01

This article features Melmark New England, a private, nonprofit, community based organization dedicated to serving children and adolescents with autism spectrum disorders, acquired brain injury, neurological diseases and disorders, and severe challenging behaviors. The Melmark parent corporation, a Pennsylvania based provider of services for those…

Advanced DNA-Based Point-of-Care Diagnostic Methods for Plant Diseases Detection.

PubMed

Lau, Han Yih; Botella, Jose R

2017-01-01

Diagnostic technologies for the detection of plant pathogens with point-of-care capability and high multiplexing ability are an essential tool in the fight to reduce the large agricultural production losses caused by plant diseases. The main desirable characteristics for such diagnostic assays are high specificity, sensitivity, reproducibility, quickness, cost efficiency and high-throughput multiplex detection capability. This article describes and discusses various DNA-based point-of care diagnostic methods for applications in plant disease detection. Polymerase chain reaction (PCR) is the most common DNA amplification technology used for detecting various plant and animal pathogens. However, subsequent to PCR based assays, several types of nucleic acid amplification technologies have been developed to achieve higher sensitivity, rapid detection as well as suitable for field applications such as loop-mediated isothermal amplification, helicase-dependent amplification, rolling circle amplification, recombinase polymerase amplification, and molecular inversion probe. The principle behind these technologies has been thoroughly discussed in several review papers; herein we emphasize the application of these technologies to detect plant pathogens by outlining the advantages and disadvantages of each technology in detail.

Advanced DNA-Based Point-of-Care Diagnostic Methods for Plant Diseases Detection

PubMed Central

Lau, Han Yih; Botella, Jose R.

2017-01-01

Diagnostic technologies for the detection of plant pathogens with point-of-care capability and high multiplexing ability are an essential tool in the fight to reduce the large agricultural production losses caused by plant diseases. The main desirable characteristics for such diagnostic assays are high specificity, sensitivity, reproducibility, quickness, cost efficiency and high-throughput multiplex detection capability. This article describes and discusses various DNA-based point-of care diagnostic methods for applications in plant disease detection. Polymerase chain reaction (PCR) is the most common DNA amplification technology used for detecting various plant and animal pathogens. However, subsequent to PCR based assays, several types of nucleic acid amplification technologies have been developed to achieve higher sensitivity, rapid detection as well as suitable for field applications such as loop-mediated isothermal amplification, helicase-dependent amplification, rolling circle amplification, recombinase polymerase amplification, and molecular inversion probe. The principle behind these technologies has been thoroughly discussed in several review papers; herein we emphasize the application of these technologies to detect plant pathogens by outlining the advantages and disadvantages of each technology in detail. PMID:29375588

Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort.

PubMed

Nevskaya, Tatiana; Baron, Murray; Pope, Janet E

2017-07-01

To estimate the effect of disease activity, as measured by the European Scleroderma Research Group Activity Index (EScSG-AI), on the risk of subsequent organ damage in a large systemic sclerosis (SSc) cohort. Of 421 SSc patients from the Canadian Scleroderma Research Group database with disease duration of ⩽ 3 years, 197 who had no evidence of end-stage organ damage initially and available 3 year follow-up were included. Disease activity was assessed by the EScSG-AI with two variability measures: the adjusted mean EScSG-AI (the area under the curve of the EScSG-AI over the observation period) and persistently active disease/flare. Outcomes were based on the Medsger severity scale and included accrual of a new severity score (Δ ⩾ 1) overall and within organ systems or reaching a significant level of deterioration in health status. After adjustment for covariates, the adjusted mean EScSG-AI was the most consistent predictor of risk across the study outcomes over 3 years in dcSSc: disease progression defined as Δ ⩾ 1 in any major internal organ, significant decline in forced vital capacity and diffusing capacity of carbon monoxide, severity of visceral disease and HAQ Disability Index worsening. In multivariate analysis, progression of lung disease was predicted solely by adjusted mean EScSG-AI, while the severity of lung disease was predicted the adjusted mean EScSG-AI, older age, modified Rodnan skin score (mRSS) and initial severity. The EScSG-AI was associated with patient- and physician-assessed measures of health status and overpowered the mRSS in predicting disease outcomes. Disease activity burden quantified with the adjusted mean EScSG-AI predicted the risk of deterioration in health status and severe organ involvement in dcSSc. The EScSG-AI is more responsive when done repeatedly and averaged. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The relationship between pain and dynamic knee joint loading in knee osteoarthritis varies with radiographic disease severity. A cross sectional study.

PubMed

Henriksen, Marius; Aaboe, Jens; Bliddal, Henning

2012-08-01

In a cross sectional study, we investigated the relationships between knee pain and mechanical loading across the knee, as indicated by the external knee adduction moment (KAM) during walking in patients with symptomatic knee OA who were distinguished by different radiographic disease severities. Data from 137 symptomatic medial knee OA patients were used. Based on Kellgren/Lawrence (K/L) grading, the patients were divided into radiographically less severe (K/L ≤ 2, n=68) or severe (K/L>2, n=69) medial knee OA. Overall knee pain was rated on a 10 cm visual analog scale, and peak KAM and KAM impulses were obtained from gait analyses. Mixed linear regression analyses were performed with KAM variables as the outcome, and pain and disease severity as independent variables, adjusting for age, gender, and walking speed. In adjusted analyses, less severe patients demonstrated negative relationships between pain intensities and dynamic loading. The severe patient group showed no relationship between pain intensity and peak KAM, and a positive relationship between pain intensity and KAM impulse. In radiographically less severe knee OA, the negative relationships between pain intensity and dynamic knee joint loading indicate a natural reaction to pain, which will limit the stress on the joint. In contrast, either absent or positive relationships between pain and dynamic loading in severe OA may lead to overuse and accelerated disease progression. These findings may have a large potential interest for strategies of treatment in knee OA. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations of childhood eczema severity: A US population based study

PubMed Central

Silverberg, Jonathan I.; Simpson, Eric L.

2014-01-01

Little is known about predictors of eczema severity in the US population. We sought to determine the distribution and associations of childhood eczema severity in the US. We analyzed data from the 2007 National Survey of Children's Health, a prospective questionnaire-based study of a nationally representative sample of 91,642 children (0-17yr). The prevalence of childhood eczema was 12.97% (95% confidence interval [95% CI]=12.42–13.53); 67.0% (95% CI: 64.8–69.2) had mild, 26.0% (95% CI: 23.9–28.1) moderate and 7.0% (95% CI: 5.8–8.3) severe disease. There was significant statewide-variation of the distribution of eczema severity (Rao-Scott chi square, P=0.004), with highest rates of severe disease in Northeastern and Midwestern states. In univariate models, eczema severity was increased with older age, African-American and Hispanic race/ethnicity, lower household income, oldest child in the family, home with a single mother, lower paternal/maternal education level, maternal general health, maternal/paternal emotional health, dilapidated housing and garbage on the streets. In multivariate survey logistic regression models using stepwise and backward selection, moderate–severe eczema was associated with older age, lower household income and fair or poor maternal health, but inversely associated with birthplace outside the US. These data indicate that environmental and/or lifestyle factors play an important role in eczema severity. PMID:24819283

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

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition].

PubMed

Maraví-Poma, E; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2014-05-01

To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and Africa. It provides a set of concise up to date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

A conceptual framework for evaluating impairments in myasthenia gravis.

PubMed

Barnett, Carolina; Bril, Vera; Kapral, Moira; Kulkarni, Abhaya; Davis, Aileen M

2014-01-01

Myasthenia gravis is characterized by weakness and fatigability of different muscle groups, including ocular, bulbar and the limbs. Therefore, a measure of disease severity at the impairment level in myasthenia needs to reflect all the relevant impairments, as well as their variations with activity and fatigue. We conducted a qualitative study of patients with myasthenia, to explore their experiences and related impairments, aimed at developing a conceptual framework of disease severity at the impairment level in myasthenia gravis. Twenty patients representing the spectrum of disease participated in semi-structured interviews. Interviews were recorded and the transcripts were analyzed by content analysis using an inductive approach with line-by-line open coding. Themes were generated from these codes. Two main themes were identified: the severity of the impairments and fatigability (i.e., triggering or worsening of an impairment with activity). The impairments were further classified within body regions (ocular, bulbar and axial/limbs). Fatigability was described as a phenomenon affecting the whole body but also affecting specific impairments, and was associated with fluctuation of the symptoms. Patients were concerned that clinical examination at a single point in time might not reflect their true clinical state due to fatigability and fluctuations in severity. This conceptual framework reflects the relevance of both severity and fatigability in understanding impairment-based disease severity in myasthenia. This framework could inform the development of impairment measures in myasthenia gravis.

Harm and the Boundaries of Disease.

PubMed

McGivern, Patrick; Sorial, Sarah

2017-08-01

What is the relationship between harm and disease? Discussions of the relationship between harm and disease typically suffer from two shortcomings. First, they offer relatively little analysis of the concept of harm itself, focusing instead on examples of clear cases of harm such as death and dismemberment. This makes it difficult to evaluate such accounts in borderline cases, where the putative harms are less severe. Second, they assume that harm-based accounts of disease must be understood normatively rather than naturalistically, in the sense that they are inherently value based. This makes such accounts vulnerable to more general objections of normative accounts of disease. Here we draw on an influential account of harm from the philosophy of law to develop a harm-based account of disease that overcomes both of these shortcomings. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analysis of Chronic Illnesses and Disability in a Community-Based Sample of Elderly People in South-Eastern Poland.

PubMed

Ćwirlej-Sozańska, Agnieszka; Wilmowska-Pietruszyńska, Anna; Sozański, Bernard; Wiśniowska-Szurlej, Agnieszka

2018-03-07

BACKGROUND The proportion of elderly people living in Poland has risen in recent years. With rising life expectancy, there is likely to be a concurrent increase in the incidence of chronic diseases and disabilities. Therefore, this study aimed to analyze the prevalence of chronic diseases and disability of the elderly in order to help guide strategies of prevention and public health control. MATERIAL AND METHODS This was a cross-sectional study of 1,000 randomly-selected residents living in the Podkarpackie region of Poland. The WHODAS 2.0 questionnaire was used to assess the disability and functioning of the participants across six domains of functioning using the following scores: no disability (0-4%), mild disability (5-24%), moderate disability (25-49%), severe disability (50-95%), and extreme disability (96-100%). RESULTS The presence of at least one chronic disease was identified in 84.1% of participants. The most common diseases were: circulatory diseases (59.10%), spinal pain syndromes (51.50%), degenerative joint diseases (50.30%), and rheumatic diseases (23.90%). Severe or extreme disability was found in 8.46% of patients with circulatory disease, 9.32% of patients with spinal pain syndromes, 9.34% of patients with degenerative joint diseases, and 12.13% of patients with rheumatic diseases. CONCLUSIONS Based on our findings, we recommend an emphasis be placed on early diagnosis of chronic diseases. We also recommend implementing methods of primary and secondary prevention aimed at reducing or eliminating disability resulting from chronic diseases. Our research highlights the need to plan targeted support and prevention programs using strategies that optimize social participation of older people with various chronic diseases.

Analysis of Chronic Illnesses and Disability in a Community-Based Sample of Elderly People in South-Eastern Poland

PubMed Central

Wilmowska-Pietruszyńska, Anna; Sozański, Bernard; Wiśniowska-Szurlej, Agnieszka

2018-01-01

Background The proportion of elderly people living in Poland has risen in recent years. With rising life expectancy, there is likely to be a concurrent increase in the incidence of chronic diseases and disabilities. Therefore, this study aimed to analyze the prevalence of chronic diseases and disability of the elderly in order to help guide strategies of prevention and public health control. Material/Methods This was a cross-sectional study of 1,000 randomly-selected residents living in the Podkarpackie region of Poland. The WHODAS 2.0 questionnaire was used to assess the disability and functioning of the participants across six domains of functioning using the following scores: no disability (0–4%), mild disability (5–24%), moderate disability (25–49%), severe disability (50–95%), and extreme disability (96–100%). Results The presence of at least one chronic disease was identified in 84.1% of participants. The most common diseases were: circulatory diseases (59.10%), spinal pain syndromes (51.50%), degenerative joint diseases (50.30%), and rheumatic diseases (23.90%). Severe or extreme disability was found in 8.46% of patients with circulatory disease, 9.32% of patients with spinal pain syndromes, 9.34% of patients with degenerative joint diseases, and 12.13% of patients with rheumatic diseases. Conclusions Based on our findings, we recommend an emphasis be placed on early diagnosis of chronic diseases. We also recommend implementing methods of primary and secondary prevention aimed at reducing or eliminating disability resulting from chronic diseases. Our research highlights the need to plan targeted support and prevention programs using strategies that optimize social participation of older people with various chronic diseases. PMID:29512628

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.

Economic effectiveness of disease management programs: a meta-analysis.

PubMed

Krause, David S

2005-04-01

The economic effectiveness of disease management programs, which are designed to improve the clinical and economic outcomes for chronically ill individuals, has been evaluated extensively. A literature search was performed with MEDLINE and other published sources for the period covering January 1995 to September 2003. The search was limited to empirical articles that measured the direct economic outcomes for asthma, diabetes, and heart disease management programs. Of the 360 articles and presentations evaluated, only 67 met the selection criteria for meta-analysis, which included 32,041 subjects. Although some studies contained multiple measurements of direct economic outcomes, only one average effect size per study was included in the meta-analysis. Based on the studies included in the research, a meta-analysis provided a statistically significant answer to the question of whether disease management programs are economically effective. The magnitude of the observed average effect size for equally weighted studies was 0.311 (95% CI = 0.272-0.350). Statistically significant differences of effect sizes by study design, disease type and intensity of disease management program interventions were not found after a moderating variable, disease severity, was taken into consideration. The results suggest that disease management programs are more effective economically with severely ill enrollees and that chronic disease program interventions are most effective when coordinated with the overall level of disease severity. The findings can be generalized, which may assist health care policy makers and practitioners in addressing the issue of providing economically effective care for the growing number of individuals with chronic illness.

Vision-Threatening Behcet's Disease: Severity of Ocular Involvement Predictors

PubMed Central

Hussein, Mohammed A.; Dahab, Ahmed A.

2018-01-01

Purpose To examine and spot systemic findings commonly associated with a serious form of ocular Behcet's disease. This could potentially help ophthalmologists categorize their patients based on future risk and plan treatment accordingly. Subjects and Methods The data of 249 patients with Behcet's disease were examined thoroughly. Correlations between systemic and ocular findings were recorded. Patients were further subgrouped by the authors as having a vision-threatening form of the disease or not. Regression analysis was done to spot predictors for a vision-threatening form of the disease. Results The presence of systemic vasculitis and oral and genital ulcers in a patient with Behcet's disease was found to be associated with a milder form of ocular affection or none at all and vice versa. Certain correlations between findings were also found. Conclusion Certain findings in Behcet's disease may act as predictors for the severity of ocular affection. Directing our attention to these factors by the internist and ophthalmologist can help plan the frequency of follow-up as well as the aggressiveness of treatment in patients with Behcet's disease. PMID:29854430

Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.

PubMed

Rajabally, Yusuf A

2017-10-01

This article focuses on the unconventional treatments used in chronic inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based treatments for CIDP include corticosteroids, immunoglobulins and plasma exchanges. Several unproven treatments are however given in treatment-refractory disease or to reduce requirements in validated therapies for reasons of side effects/practical delivery/cost. Despite methodological issues, IFN-α, azathioprine and methotrexate have not been shown to be useful in randomized controlled trials. Cyclophosphamide, rituximab and, as final resort in highly selected cases, hematopoietic stem cell transplant may be options considered in severely disabled refractory patients. Debatably, azathioprine, methotrexate, cyclosporine and mycophenolate mofetil are still occasionally used, among others, in milder disease. Physical therapy may be of benefit in CIDP but is not systematically considered as an integral part of management strategies. Current literature relating to unconventional therapies in CIDP is reviewed here and the possible avenues that require consideration in severe refractory disease and less disabling forms are discussed.

Rethinking Strategies to Select Antibiotic Therapy in Clostridium difficile infection.

PubMed

Chopra, Teena; Goldstein, Ellie J C; Gorbach, Sherwood L

2016-12-01

In recent years, Clostridium difficile infection (CDI) has become a global public health threat associated with increased morbidity, mortality, and economic burden, all of which are exacerbated with disease recurrence. Current guidelines informing treatment decisions are largely based on definitions of disease severity at diagnosis, with subjective components not well delineated across treatment algorithms and clinical trials. Furthermore, there is little evidence linking severity at onset to outcome. However, reducing the risk of recurrence may offer both a better outcome for the individual and decreased downstream economic impact. The authors present data supporting the opinion that patients deemed at low risk for recurrence should receive vancomycin (or metronidazole when cost is an issue), while those at higher risk of recurrence would benefit from fidaxomicin treatment. Although further prospective studies are needed, choosing treatment with the goal of preventing recurrent CDI may offer a better guide than disease severity. © 2016 Pharmacotherapy Publications, Inc.

Experimental reproduction of necrotic enteritis in chickens: a review.

PubMed

Prescott, John F; Smyth, Joan A; Shojadoost, Bahram; Vince, Andrew

2016-06-01

This review discusses key factors important in successful experimental reproduction of necrotic enteritis (NE) in chickens, and how these factors can be adjusted to affect the severity of the lesions induced. The critical bacterial factor is the need to use virulent, netB-positive, strains of Clostridium perfringens; disease severity can be enhanced by using netB-positive C. perfringens strains that are also tpeL-positive, by the use of young rather than old broth cultures, and by the number of days of inoculation and the number of bacteria used. Use of cereals rich in non-starch polysaccharides can enhance disease, as does use of animal proteins. Administration of coccidia, including coccidial vaccines, combined with netB-positive C. perfringens, increases the severity of experimentally-induced NE. Dietary manipulation may be less important in coccidia-based models since the latter are so effective. Disease scoring systems and welfare considerations are discussed.

Oral-Fluid Thiol-Detection Test Identifies Underlying Active Periodontal Disease Not Detected by the Visual Awake Examination.

PubMed

Queck, Katherine E; Chapman, Angela; Herzog, Leslie J; Shell-Martin, Tamara; Burgess-Cassler, Anthony; McClure, George David

Periodontal disease in dogs is highly prevalent but can only be accurately diagnosed by performing an anesthetized oral examination with periodontal probing and dental radiography. In this study, 114 dogs had a visual awake examination of the oral cavity and were administered an oral-fluid thiol-detection test prior to undergoing a a full-mouth anesthetized oral examination and digital dental radiographs. The results show the visual awake examination underestimated the presence and severity of active periodontal disease. The thiol-detection test was superior to the visual awake examination at detecting the presence and severity of active periodontal disease and was an indicator of progression toward alveolar bone loss. The thiol-detection test detected active periodontal disease at early stages of development, before any visual cues were present, indicating the need for intervention to prevent periodontal bone loss. Early detection is important because without intervention, dogs with gingivitis (active periodontal disease) progress to irreversible periodontal bone loss (stage 2+). As suggested in the current AAHA guidelines, a thiol-detection test administered in conjunction with the visual awake examination during routine wellness examinations facilitates veterinarian-client communication and mitigates under-diagnosis of periodontal disease and underutilization of dental services. The thiol-detection test can be used to monitor the periodontal health status of the conscious patient during follow-up examinations based on disease severity.

Empirical Wavelet Transform Based Features for Classification of Parkinson's Disease Severity.

PubMed

Oung, Qi Wei; Muthusamy, Hariharan; Basah, Shafriza Nisha; Lee, Hoileong; Vijean, Vikneswaran

2017-12-29

Parkinson's disease (PD) is a type of progressive neurodegenerative disorder that has affected a large part of the population till now. Several symptoms of PD include tremor, rigidity, slowness of movements and vocal impairments. In order to develop an effective diagnostic system, a number of algorithms were proposed mainly to distinguish healthy individuals from the ones with PD. However, most of the previous works were conducted based on a binary classification, with the early PD stage and the advanced ones being treated equally. Therefore, in this work, we propose a multiclass classification with three classes of PD severity level (mild, moderate, severe) and healthy control. The focus is to detect and classify PD using signals from wearable motion and audio sensors based on both empirical wavelet transform (EWT) and empirical wavelet packet transform (EWPT) respectively. The EWT/EWPT was applied to decompose both speech and motion data signals up to five levels. Next, several features are extracted after obtaining the instantaneous amplitudes and frequencies from the coefficients of the decomposed signals by applying the Hilbert transform. The performance of the algorithm was analysed using three classifiers - K-nearest neighbour (KNN), probabilistic neural network (PNN) and extreme learning machine (ELM). Experimental results demonstrated that our proposed approach had the ability to differentiate PD from non-PD subjects, including their severity level - with classification accuracies of more than 90% using EWT/EWPT-ELM based on signals from motion and audio sensors respectively. Additionally, classification accuracy of more than 95% was achieved when EWT/EWPT-ELM is applied to signals from integration of both signal's information.

Clinical trials validate the severity of persistent Lyme disease symptoms.

PubMed

Cameron, Daniel J

2009-02-01

Persistent Lyme Disease Symptoms (PLDS) have included fatigue, headaches, poor concentration and memory, lightheadedness, joint pain, and mood disturbances. Evidence-based guidelines committees disagree over the severity of PLDS. The 2004 International Lyme and Associated Diseases Society (ILADS) concluded that PLDS are severe. The 2006 Infectious Disease Society of America (IDSA) guidelines committee concluded that PLDS are nothing more than the "aches and pains of daily living" and an ad hoc International Lyme group concluded that PLDS are "symptoms common in persons who have never had Lyme disease." Clinical trials validate the severity of persistent Lyme disease symptoms. There are 22 standardized instruments used to measure the severity of PLDS among the four published National Institutes of Health (NIH) sponsored double-blind randomized placebo-controlled trials (RCTs). VALIDATING THE HYPOTHESIS: All four NIH sponsored RCTs validate the severity of PLDS. PLDS are as severe as symptoms seen in other serious chronic illnesses, and result in a quality of life lower than for the general population as determined by 22 standardized measures of QOL, including fatigue, pain, role function, psychopathology, and cognition. None of the four RCTs support the IDSA hypothesis that PLDS are nothing more than "the aches and pains of daily living" nor the ad hoc International Lyme group conclusion that PLDS are "symptoms common in persons who have never had Lyme disease." If the QOL of life for these patients is as poor as for patients with other serious chronic diseases, their symptoms need to be addressed by their doctors. Studies differ as to the precise cause of PLDS, the most effective treatments, and whether a cure is possible. But the fact that there is disagreement is not a license for physicians to ignore or turn away patients complaining of PLDS, or to dismiss their symptoms as purely psychosomatic. For physicians, the goal or purpose of treating PLDS should be the same as their purpose in treating other chronic illnesses that result in a poor QOL: vigorous pursuit of a cure, and where a cure proves impossible, amelioration of patients' symptoms and suffering. Even if this hypothesis fails to be apply to more than a fraction of the total Lyme disease population, this still represents a significant number of patients, and these findings could address a neglected aspect of caring for patients with Lyme disease.

Bootstrap imputation with a disease probability model minimized bias from misclassification due to administrative database codes.

PubMed

van Walraven, Carl

2017-04-01

Diagnostic codes used in administrative databases cause bias due to misclassification of patient disease status. It is unclear which methods minimize this bias. Serum creatinine measures were used to determine severe renal failure status in 50,074 hospitalized patients. The true prevalence of severe renal failure and its association with covariates were measured. These were compared to results for which renal failure status was determined using surrogate measures including the following: (1) diagnostic codes; (2) categorization of probability estimates of renal failure determined from a previously validated model; or (3) bootstrap methods imputation of disease status using model-derived probability estimates. Bias in estimates of severe renal failure prevalence and its association with covariates were minimal when bootstrap methods were used to impute renal failure status from model-based probability estimates. In contrast, biases were extensive when renal failure status was determined using codes or methods in which model-based condition probability was categorized. Bias due to misclassification from inaccurate diagnostic codes can be minimized using bootstrap methods to impute condition status using multivariable model-derived probability estimates. Copyright © 2017 Elsevier Inc. All rights reserved.

Personalized Medicine in Allergic Asthma: At the Crossroads of Allergen Immunotherapy and "Biologicals".

PubMed

Fritzsching, Benedikt

2017-01-01

Major allergic disease can be viewed as clinical syndromes rather than discrete disease entities. Emerging evidence indicates that allergic asthma includes several disease phenotypes. Immunological deviation toward high T helper cell type 2 cytokine levels has been demonstrated for a subgroup of pediatric asthma patients, and now, several novel monoclonal antibodies have been approved for treatment of this subgroup as a stratified approach of "personalized" medicine in allergy. Introduction of component-based IgE testing before allergen immunotherapy (AIT), i.e., testing for IgE cross-reactivity before initiation of AIT, has also brought stratified medicine into allergy therapy. Improved responder criteria, which identify treatment-responders previous to therapy, might foster this stratification and even individualized AIT might have an impact for tailor-made therapy in the future. Furthermore, combining antibody-based treatment with AIT could help to establish more rapid AIT protocols even for allergens with a high risk of anaphylactic reactions. Efforts to advance such "personalized" medicine in pediatric allergy might be challenged by several issues including high costs for the health-care system, increasing complexity of allergy therapy, the need for physician allergy expertise, and furthermore ethical considerations and data safety issues.

Wrist sensor-based tremor severity quantification in Parkinson's disease using convolutional neural network.

PubMed

Kim, Han Byul; Lee, Woong Woo; Kim, Aryun; Lee, Hong Ji; Park, Hye Young; Jeon, Hyo Seon; Kim, Sang Kyong; Jeon, Beomseok; Park, Kwang S

2018-04-01

Tremor is a commonly observed symptom in patients of Parkinson's disease (PD), and accurate measurement of tremor severity is essential in prescribing appropriate treatment to relieve its symptoms. We propose a tremor assessment system based on the use of a convolutional neural network (CNN) to differentiate the severity of symptoms as measured in data collected from a wearable device. Tremor signals were recorded from 92 PD patients using a custom-developed device (SNUMAP) equipped with an accelerometer and gyroscope mounted on a wrist module. Neurologists assessed the tremor symptoms on the Unified Parkinson's Disease Rating Scale (UPDRS) from simultaneously recorded video footages. The measured data were transformed into the frequency domain and used to construct a two-dimensional image for training the network, and the CNN model was trained by convolving tremor signal images with kernels. The proposed CNN architecture was compared to previously studied machine learning algorithms and found to outperform them (accuracy = 0.85, linear weighted kappa = 0.85). More precise monitoring of PD tremor symptoms in daily life could be possible using our proposed method. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Mitochondrial Neuro-Gastro-Intestinal Encephalopathy (MNGIE): When and how to suspect it in front of an atypical anorexia nervosa?

PubMed

Danjou, M; Guardia, D; Geoffroy, P-A; Seguy, D; Cottencin, O

2016-12-01

The Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) disease is an extremely underrated syndrome beginning around the age of eighteen years. Because of its severity, this diagnosis should be considered when a patient presents an atypical anorexia nervosa. MNGIE disease is inherited in an autosomal recessive manner and related to mutations of the TYMP gene (ch22q13.32-qter), encoding the thymidine phosphorylase. The MNGIE is often misdiagnosed and is associated with a time to diagnostic of about 12 years after first symptoms. Thus this critical review aims to help clinicians better identify symptoms and paraclinical markers of the MNGIE as a differential diagnosis of atypical anorexia nervosa. A literature search was performed using PubMed and Google Scholar databases. The clinical diagnosis of the MNGIE disease should be based on the association of severe loss of weight and some additional symptoms: (1) severe gastrointestinal dysmotility (nausea, vomiting, intestinal pseudo-obstruction), (2) ptosis or external ophtalmoplegia and (3) peripheral sensorimotor neuropathy. When MNGIE disease is clinically suspected, paraclinical testing can help to validate the MNGIE diagnostic: (1) Arterial blood test reveals lactic acidemia (e.g. an increased serum concentration of lactate without pH modifications), and (2) Brain MRI indicates leukoencephalopathy, usually asymptomatic. Direct evidence of MNGIE disease is based on specific testing of: (1) the thymidine phopshorylase enzyme activity in leukocytes is less than 10% of the control, (2) the increase of plasmatic thymidine (>3μmol/L) and the increase of plamatic deoxyuridine (>5μmol/L), (3) the evidence of mutations of the TYMP gene by molecular genetic testing. The MNGIE disease is a severe trouble with multisystemic complications. The thymidine phopshorylase enzyme activity in leukocytes should be measured as soon as possible when a patient presents atypical anorexia nervosa. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs).

PubMed

Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Baasov, Timor; Wolfrum, Uwe

2016-04-01

In recent years, remarkable advances in the ability to diagnose genetic disorders have been made. The identification of disease-causing genes allows the development of gene-specific therapies with the ultimate goal to develop personalized medicines for each patient according to their own specific genetic defect. In-depth genotyping of many different genes has revealed that ~12% of inherited genetic disorders are caused by in-frame nonsense mutations. Nonsense (non-coding) mutations are caused by point mutations, which generate premature termination codons (PTCs) that cause premature translational termination of the mRNA, and subsequently inhibit normal full-length protein expression. Recently, a gene-based therapeutic approach for genetic diseases caused by nonsense mutations has emerged, namely the so-called translational read-through (TR) therapy. Read-through therapy is based on the discovery that small molecules, known as TR-inducing drugs (TRIDs), allow the translation machinery to suppress a nonsense codon, elongate the nascent peptide chain, and consequently result in the synthesis of full-length protein. Several TRIDs are currently under investigation and research has been performed on several genetic disorders caused by nonsense mutations over the years. These findings have raised hope for the usage of TR therapy as a gene-based pharmacogenetic therapy for nonsense mutations in various genes responsible for a variety of genetic diseases.

Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever.

PubMed

Akinci, Esragul; Bodur, Hurrem; Sunbul, Mustafa; Leblebicioglu, Hakan

2016-08-01

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

PubMed

Gibson, P G; Reddel, H; McDonald, V M; Marks, G; Jenkins, C; Gillman, A; Upham, J; Sutherland, M; Rimmer, J; Thien, F; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Robinson, P; Wright, C; Yozghatlian, V; Burgess, S; Sivakumaran, P; Jaffe, A; Bowden, J; Wark, P A B; Yan, K Y; Kritikos, V; Peters, M; Hew, M; Aminazad, A; Bint, M; Guo, M

2016-09-01

Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting. © 2016 Royal Australasian College of Physicians.

Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

PubMed

Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

2015-01-01

In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

Effectiveness of two community-based strategies on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia in Ghana.

PubMed

Escribano-Ferrer, Blanca; Gyapong, Margaret; Bruce, Jane; Narh Bana, Solomon A; Narh, Clement T; Allotey, Naa-Korkor; Glover, Roland; Azantilow, Charity; Bart-Plange, Constance; Sagoe-Moses, Isabella; Webster, Jayne

2017-12-12

Ghana has developed two community-based strategies that aim to increase access to quality treatment for malaria, diarrhoea and suspected pneumonia, and to improve household and family practices: integrated Community Case Management (iCCM) and Community-based Health Planning and Services (CHPS). The objective of the study was to assess the effectiveness of iCCM and CHPS on disease knowledge and health behaviour regarding malaria, diarrhoea and pneumonia. A household survey was conducted two and eight years after implementation of iCCM in the Volta and Northern Regions of Ghana respectively, and more than ten years of CHPS implementation in both regions. The study population included 1356 carers of children under- five years of age who had fever, diarrhoea and/or cough in the two weeks prior to the interview. Disease knowledge was assessed based on the knowledge of causes and identification of signs of severe disease and its association with the sources of health education messages received. Health behaviour was assessed based on reported prompt care seeking behaviour, adherence to treatment regime, utilization of mosquito nets and having improved sanitation facilities, and its association with the sources of health education messages received. Health education messages from community-based agents (CBAs) in the Northern Region were associated with the identification of at least two signs of severe malaria (adjusted Odds Ratio (OR) 1.8, 95%CI 1.0, 3.3, p = 0.04), two practices that can cause diarrhoea (adjusted OR 4.7, 95%CI 1.4, 15.5, p = 0.02) 0and two signs of severe pneumonia (adjusted OR 7.7, 95%CI2.2, 26.5, p = 0.01)-the later also associated with prompt care seeking behaviour (p = 0.04). In the Volta Region, receiving messages on diarrhoea from CHPS was associated with the identification of at least two signs of severe diarrhoea (adjusted OR 3.6, 95%CI 1.4, 9.0), p = 0.02). iCCM was associated with prompt care seeking behaviour in the Volta Region and CHPS with prompt care seeking behaviour in the Northern Region (p < 0.5). Both iCCM and CHPS were associated with disease knowledge and health behaviour, but this was more pronounced for iCCM and in the Northern Region. HBC should continue to be considered as the strategy through which community-IMCI is implemented.

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.

Adeno-Associated Virus–Mediated Gene Therapy for Metabolic Myopathy

PubMed Central

Mah, Cathryn S.; Soustek, Meghan S.; Todd, A. Gary; McCall, Angela; Smith, Barbara K.; Corti, Manuela; Falk, Darin J.

2013-01-01

Abstract Metabolic myopathies are a diverse group of rare diseases in which impaired breakdown of stored energy leads to profound muscle dysfunction ranging from exercise intolerance to severe muscle wasting. Metabolic myopathies are largely caused by functional deficiency of a single gene and are generally subcategorized into three major types of metabolic disease: mitochondrial, lipid, or glycogen. Treatment varies greatly depending on the biochemical nature of the disease, and unfortunately no definitive treatments exist for metabolic myopathy. Since this group of diseases is inherited, gene therapy is being explored as an approach to personalized medical treatment. Adeno-associated virus–based vectors in particular have shown to be promising in the treatment of several forms of metabolic myopathy. This review will discuss the most recent advances in gene therapy efforts for the treatment of metabolic myopathies. PMID:24164240

Neglected parasitic infections in the United States: toxoplasmosis.

PubMed

Jones, Jeffrey L; Parise, Monica E; Fiore, Anthony E

2014-05-01

Toxoplasma gondii is a leading cause of severe foodborne illness in the United States. Population-based studies have found T. gondii infection to be more prevalent in racial/ethnic minority and socioeconomically disadvantaged groups. Soil contaminated with cat feces, undercooked meat, and congenital transmission are the principal sources of infection. Toxoplasmosis-associated illnesses include congenital neurologic and ocular disease; acquired illness in immunocompetent persons, most notably ocular disease; and encephalitis or disseminated disease in immunosuppressed persons. The association of T. gondii infection with risk for mental illness is intriguing and requires further research. Reduction of T. gondii in meat, improvements in hygiene and food preparation practices, and reduction of environmental contamination can prevent toxoplasmosis, but more research is needed on how to implement these measures. In addition, screening and treatment may help prevent toxoplasmosis or reduce the severity of disease in some settings.

Correlations of chemokine CXCL16 and TNF-α with coronary atherosclerotic heart disease.

PubMed

Xing, Jieyong; Liu, Yanshao; Chen, Tao

2018-01-01

This study determined the correlations of CXC ligand 16 (CXCL16) and tumor necrosis factor-α (TNF-α) levels with coronary atherosclerotic heart disease (CAHD) and screened for new clinical markers for the prognosis and treatment of the disease. Eighty patients with coronary heart disease and 50 healthy subjects were enrolled into a CAHD or healthy control group, respectively. Computed tomography (CT) coronary angiography and Gensini integral were used to classify plaques and evaluate patients with coronary heart disease. The serum levels of CXCL16 and TNF-α of subjects in each group were detected by enzyme-linked immunosorbent assays (ELISA), and the correlation between levels and clinical markers (such as blood pressure, glucose, lipid and heart rate) and the severity of disease were analyzed. Our results showed the serum levels of CXCL16 and TNF-α were significantly higher in the CAHD group than those in the CK group. The serum CXCL16 levels of the CAHD group patients with plaques were distinctly higher than those of the CADH group patients without plaques, but there were no significant difference in serum TNF-α levels between these two groups of patients. The level of CXCL16 had a significantly positive correlation with the severity of disease, but there was no significant correlation between TNF-α level and the severity of disease. Also, there was no significant correlation between the CXCL16 levels and blood pressure, blood glucose, heart rate, total cholesterol, triglyceride or high-density lipoprotein cholesterol, but there was a clear correlation with the low-density lipoprotein cholesterol. Finally no significant correlations were found between TNF-α levels and each of the clinical markers studied. Based on our findings, the levels of CXCL16 and TNF-α in the patients with coronary heart disease were abnormally increased and the level of CXCL16 correlated closely with the severity of disease. These markers seem to be reliable biological markers for prognosis and disease evaluation in coronary heart disease patients.

Strong ion and weak acid analysis in severe preeclampsia: potential clinical significance.

PubMed

Ortner, C M; Combrinck, B; Allie, S; Story, D; Landau, R; Cain, K; Dyer, R A

2015-08-01

The influence of common disturbances seen in preeclampsia, such as changes in strong ions and weak acids (particularly albumin) on acid-base status, has not been fully elucidated. The aims of this study were to provide a comprehensive acid-base analysis in severe preeclampsia and to identify potential new biological predictors of disease severity. Fifty women with severe preeclampsia, 25 healthy non-pregnant- and 46 healthy pregnant controls (26-40 weeks' gestation), were enrolled in this prospective case-control study. Acid-base analysis was performed by applying the physicochemical approach of Stewart and Gilfix. Mean [sd] base excess was similar in preeclamptic- and healthy pregnant women (-3.3 [2.3], and -2.8 [1.5] mEq/L respectively). In preeclampsia, there were greater offsetting contributions to the base excess, in the form of hyperchloraemia (BE(Cl) -2 [2.3] vs -0.4 [2.3] mEq/L, P<0.001) and hypoalbuminaemia (BE(Alb) 3.6 [1] vs 2.1 [0.8] mEq/L, P<0.001). In preeclampsia, hypoalbuminaemic metabolic alkalosis was associated with a non-reassuring/abnormal fetal heart tracing (P<0.001). Quantitative analysis in healthy pregnancy revealed respiratory and hypoalbuminaemic alkalosis that was metabolically offset by acidosis, secondary to unmeasured anions and dilution. While the overall base excess in severe preeclampsia is similar to that in healthy pregnancy, preeclampsia is associated with a greater imbalance offsetting hypoalbuminaemic alkalosis and hyperchloraemic acidosis. Rather than the absolute value of base excess, the magnitude of these opposing contributors may be a better indicator of the severity of this disease. Hypoalbuminaemic alkalosis may also be a predictor of fetal compromise. clinicaltrials.gov: NCT 02164370. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of nutritional status in patients with Parkinson's disease and its relationship with severity of the disease.

PubMed

Shidfar, Farzad; Babaii Darabkhani, Peivand; Yazdanpanah, Leila; Karkheiran, Siamak; Noorollahi-Moghaddam, Hamid; Haghani, Hamid

2016-01-01

Background: Malnutrition, loss of body weight, muscle and fat mass wasting are common in patients with Parkinson's disease, and are associated with disability, longer length of hospital stay, impaired immune system and increased risk of mortality. The aim of this study was to assess the nutritional status in patients with Parkinson's disease and its relation to the severity of the disease. Methods: This cross- sectional study was conducted on 130 patients with Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status, and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used to determine the severity of the disease. One-way ANOVA test was used to assess the relationship between anthropometric indices, nutritional status and severity of disease. Assessment of the relationship between age, duration of disease and nutritional status was categorized according to MNA score, and was performed, using one-way ANOVA. Chi - Square test was utilized to assess the relationship between education level and nutritional status. SPSS Version 18 was used for data analysis. Results: In this study, 30% (n=39) of the participants were diagnosed with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and 11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle mass wasting was observed in different disease stages. Muscle mass wasting and worsening nutritional status, based on MNA score, showed a significant increase as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing the relationship between education level, age, duration of disease with nutritional status, the results revealed a significant relationship between age (p=0.008), education level (p<0.001) with nutritional status according to MNA score. Conclusion: Reduction of BMI, depletion of muscle mass, and worsening of nutritional status according to MNA, was observed in many patients along with an increase in the severity of the disease. Assessing nutritional status in those with Parkinson's disease to provide information to identify necessary nutritional intervention is highly recommended.

Opportunities and challenges of disease biomarkers: a new section in the Journal of Translational Medicine.

PubMed

Wang, Xiangdong; Ward, Peter A

2012-12-05

Disease biomarkers are defined to diagnose various phases of diseases, monitor severities of diseases and responses to therapies, or predict prognosis of patients. Disease-specific biomarkers should benefit drug discovery and development, integrate multidisciplinary sciences, be validated by molecular imaging. The opportunities and challenges in biomarker development are emphasized and considered. The Journal of Translational Medicine opens a new Section of Disease Biomarkers to bridge identification and validation of gene or protein-based biomarkers, network biomarkers, dynamic network biomarkers in human diseases, patient phenotypes, and clinical applications. Disease biomarkers are also important for determining drug effects, target specificities and binding, dynamic metabolism and pharmacological kinetics, or toxicity profiles.

Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease

PubMed Central

Herrmann, Nathan; Gauthier, Serge

2008-01-01

Background The management of severe Alzheimer disease often presents difficult choices for clinicians and families. The disease is characterized by a need for full-time care and assistance with basic activities of daily living. We outline an evidence-based approach for these choices based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Methods We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of severe Alzheimer disease. Subsequent to the conference, we searched for additional articles published from January 2006 to March 2008 using the same search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care. Results We identified 940 articles, of which 838 were selected for further study. Thirty-four articles were judged to be of at least good or fair quality and were used to generate 17 recommendations. Assessment of severe Alzheimer disease should include the measurement of cognitive function and the assessment of behaviour, function, medical status, nutrition, safety and caregiver status. Management could include treatment with a cholinesterase inhibitor or memantine, or both. Treatment of neuropsychiatric symptoms begins with nonpharmacologic approaches to addressing behavioural problems. Severe agitation, aggression and psychosis, which are potentially dangerous to the patient, the caregiver and others in the environment, can be treated with atypical antipsychotics, with consideration of their increased risk of cerebrovascular events and death. All pharmacologic approaches require careful monitoring and periodic reassessment to determine whether continued treatment is necessary. Caregiver support and use of community resources are essential. Interpretation Severe Alzheimer disease requires frequent monitoring by health professionals. Simple nonpharmacologic approaches may address problems with mood and agitation. Antipsychotic drug therapy is occasionally necessary despite the inherent risks. Therapy with a cholinesterase inhibitor and memantine may be useful for selected patients. Articles to date in this series Chertkow H. Diagnosis and treatment of dementia: Introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. CMAJ 2008;178:316-21. Patterson C, Feightner JW, Garcia A, et al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-56. Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-36. Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178: 1273-85. Hogan DB, Bailey P, Black S, et al. Diagnosis and treatment of dementia: 4. Approach to management of mild to moderate dementia. CMAJ 2008;179:787-93. Hogan DB, Bailey P, Black S, et al. Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia. CMAJ 2008;179:1019-26. PMID:19047609

Scab severity in relation to hedge pruning pecan trees in the Southeastern USA

USDA-ARS?s Scientific Manuscript database

Scab is the most damaging disease of pecan in the Southeastern USA. Pecan trees are tall (up to 30+ m), and managing disease in the upper canopy is problematic. Hedge pruning trees to ~12 m is being explored to facilitate efficacy of ground-based fungicide sprays, but resulting vigorous shoot growth...

Drug Target Prediction and Repositioning Using an Integrated Network-Based Approach

PubMed Central

Emig, Dorothea; Ivliev, Alexander; Pustovalova, Olga; Lancashire, Lee; Bureeva, Svetlana; Nikolsky, Yuri; Bessarabova, Marina

2013-01-01

The discovery of novel drug targets is a significant challenge in drug development. Although the human genome comprises approximately 30,000 genes, proteins encoded by fewer than 400 are used as drug targets in the treatment of diseases. Therefore, novel drug targets are extremely valuable as the source for first in class drugs. On the other hand, many of the currently known drug targets are functionally pleiotropic and involved in multiple pathologies. Several of them are exploited for treating multiple diseases, which highlights the need for methods to reliably reposition drug targets to new indications. Network-based methods have been successfully applied to prioritize novel disease-associated genes. In recent years, several such algorithms have been developed, some focusing on local network properties only, and others taking the complete network topology into account. Common to all approaches is the understanding that novel disease-associated candidates are in close overall proximity to known disease genes. However, the relevance of these methods to the prediction of novel drug targets has not yet been assessed. Here, we present a network-based approach for the prediction of drug targets for a given disease. The method allows both repositioning drug targets known for other diseases to the given disease and the prediction of unexploited drug targets which are not used for treatment of any disease. Our approach takes as input a disease gene expression signature and a high-quality interaction network and outputs a prioritized list of drug targets. We demonstrate the high performance of our method and highlight the usefulness of the predictions in three case studies. We present novel drug targets for scleroderma and different types of cancer with their underlying biological processes. Furthermore, we demonstrate the ability of our method to identify non-suspected repositioning candidates using diabetes type 1 as an example. PMID:23593264

A Comparison of Diarrheal Severity Scores in the MAL-ED Multisite Community-Based Cohort Study

PubMed Central

Lee, Gwenyth O.; Richard, Stephanie A.; Kang, Gagandeep; Houpt, Eric R.; Seidman, Jessica C.; Pendergast, Laura L.; Bhutta, Zulfiqar A.; Ahmed, Tahmeed; Mduma, Estomih R.; Lima, Aldo A.; Bessong, Pascal; Jennifer, Mats Steffi; Hossain, Md. Iqbal; Chandyo, Ram Krishna; Nyathi, Emanuel; Lima, Ila F.; Pascal, John; Soofi, Sajid; Ladaporn, Bodhidatta; Guerrant, Richard L.; Caulfield, Laura E.; Black, Robert E.; Kosek, Margaret N.

2016-01-01

ABSTRACT Objectives: There is a lack of consensus on how to measure diarrheal severity. Within the context of a multisite, prospective cohort study, we evaluated the performance of a modified Vesikari score (MAL-ED), 2 previously published scores (Clark and CODA [a diarrheal severity score (Community DiarrheA) published by Lee et al]), and a modified definition of moderate-to-severe diarrhea (MSD) based on dysentery and health care worker diagnosed dehydration. Methods: Scores were built using maternally reported symptoms or fieldworker-reported clinical signs obtained during the first 7 days of a diarrheal episode. The association between these and the risk of hospitalization were tested using receiver operating characteristic analysis. Severity scores were also related to illness etiology, and the likelihood of the episode subsequently becoming prolonged or persistent. Results: Of 10,159 episodes from 1681 children, 143 (4.0%) resulted in hospitalization. The area under the curve of each score as a predictor of hospitalization was 0.84 (95% confidence interval: 0.81, 0.87) (Clark), 0.85 (0.82, 0.88) (MAL-ED), and 0.87 (0.84, 0.89) (CODA). Severity was also associated with etiology and episode duration. Although families were more likely to seek care for severe diarrhea, approximately half of severe cases never reached the health system. Conclusions: Community-based diarrheal severity scores are predictive of relevant child health outcomes. Because they require no assumptions about health care access or utilization, they are useful in refining estimates of the burden of diarrheal disease, in estimating the effect of disease control interventions, and in triaging children for referral in low- and middle-income countries in which the rates of morbidity and mortality after diarrhea remain high. PMID:27347723

ORIGIN AND DEVELOPMENT OF AYURVEDA: (A BRIEF HISTORY)

PubMed Central

Narayanaswamy, V.

1981-01-01

History of medicine is a fascinating subject as it is a saga of man's struggle against disease. As the civilization advances and as the disease pattern changes, the medical science also changes. Ayurveda is the system of medicine that evolved in India with a rationale logical foundation and it has survived as a distinct entity from remote antiquity to the present day. The fundamentals on which the Ayurvedic system is based are essentially true for all times and do not change from are to age. These are based on human actors, on intrinsic causes. The origin of Ayurveda is attributed to Atharva Veda where mention is made several diseases with their treatments. Later, from the 6th Century BC to 7th Century AD there was systematic development of the science and it is called Samhita period, when a number of classical works were produced by several authors and during this period there is evidence of organized medical care. PMID:22556454

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

The Association Between Geographic Density of Infectious Disease Physicians and Limb Preservation in Patients With Diabetic Foot Ulcers.

PubMed

Brennan, Meghan B; Allen, Glenn O; Ferguson, Patrick D; McBride, Joseph A; Crnich, Christopher J; Smith, Maureen A

2017-01-01

Avoiding major (above-ankle) amputation in patients with diabetic foot ulcers is best accomplished by multidisciplinary care teams with access to infectious disease specialists. However, access to infectious disease physicians is partially influenced by geography. We assessed the effect of living in a hospital referral region with a high geographic density of infectious disease physicians on major amputation for patients with diabetic foot ulcers. We studied geographic density, rather than infectious disease consultation, to capture both the direct and indirect (eg, informal consultation) effects of access to these providers on major amputation. We used a national retrospective cohort of 56440 Medicare enrollees with incident diabetic foot ulcers. Cox proportional hazard models were used to assess the relationship between infectious disease physician density and major amputation, while controlling for patient demographics, comorbidities, and ulcer severity. Living in hospital referral regions with high geographic density of infectious disease physicians was associated with a reduced risk of major amputation after controlling for demographics, comorbidities, and ulcer severity (hazard ratio, .83; 95% confidence interval, .75-.91; P < .001). The relationship between the geographic density of infectious disease physicians and major amputation was not different based on ulcer severity and was maintained when adjusting for socioeconomic factors and modeling amputation-free survival. Infectious disease physicians may play an important role in limb salvage. Future studies should explore whether improved access to infectious disease physicians results in fewer major amputations. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Detailed analysis of the supermarket task included on the Japanese version of the Rapid Dementia Screening Test.

PubMed

Moriyama, Yasushi; Yoshino, Aihide; Muramatsu, Taro; Mimura, Masaru

2017-05-01

The supermarket task, which is included in the Japanese version of the Rapid Dementia Screening Test, requires the quick (1 min) generation of words for things that can be bought in a supermarket. Cluster size and switches are investigated during this task. We investigated how the severity of dementia related to cluster size and switches on the supermarket task in patients with Alzheimer's disease. We administered the Japanese version of the Rapid Dementia Screening Test to 250 patients with very mild to severe Alzheimer's disease and to 49 healthy volunteers. Patients had Mini-Mental State Examination scores from 12 to 26 and Clinical Dementia Rating scale scores from 0.5 to 3. Patients were divided into four groups based on their Clinical Dementia Rating score (0.5, 1, 2, 3). We performed statistical analyses between the four groups and control subjects based on cluster size and switch scores on the supermarket task. The score for cluster size and switches deteriorated according to the severity of dementia. Moreover, for subjects with a Clinical Dementia Rating score of 0.5, cluster size was impaired, but switches were intact. Our findings indicate that the scores for cluster size and switches on the supermarket task may be useful for detecting the severity of symptoms of dementia in patients with Alzheimer's disease. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

Prevalence, Duration and Severity of Parkinson's Disease in Germany: A Combined Meta-Analysis from Literature Data and Outpatient Samples.

PubMed

Enders, Dirk; Balzer-Geldsetzer, Monika; Riedel, Oliver; Dodel, Richard; Wittchen, Hans-Ulrich; Sensken, Sven-Christian; Wolff, Björn; Reese, Jens-Peter

2017-01-01

Epidemiological data on the prevalence of Parkinson's disease (PD) in Germany are limited. The aims of this study were to estimate the age- and gender-specific prevalence of PD in Germany as well as the severity and illness duration. A systematic literature search was performed in 5 different databases. European studies were included if they reported age- and gender-specific numbers of prevalence rates of PD. Meta-analytic approaches were applied to derive age- and gender-specific pooled prevalence estimates. Data of 4 German outpatient samples were incorporated to calculate the proportion of patients with PD in Germany grouped by Hoehn and Yahr (HY) stages and disease duration. In the German population, 178,169 cases of PD were estimated (prevalence: 217.22/100,000). The estimated relative illness duration was 40% with less than 5 years, 31% with 5-9 years, and 29% with more than 9 years. The proportions for different HY stages were estimated at 13% (I), 30% (II), 35% (III), 17% (IV), and 4% (V), respectively. Key Message: We provide an up-to-date estimation of age- and gender-specific as well as severity-based prevalence figures for PD in Germany. Further community studies are needed to estimate population-based severity distributions and distributions of non-motor symptoms in PD. © 2017 S. Karger AG, Basel.

Verification of the new grading scale for ocular chronic graft-versus-host disease developed by the German-Austrian-Swiss consensus conference on chronic GVHD.

PubMed

Blecha, Christiane; Wolff, Daniel; Holler, Barbara; Holler, Ernst; Weber, Daniela; Vogt, Regine; Helbig, Horst; Dietrich-Ntoukas, Tina

2016-02-01

The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications.

[Financial cost of early rheumatoid arthritis in the first year of medical attention: three clinical scenarios in a third-tier university hospital in Colombia].

PubMed

Mora, Claudia; González, Andrés; Díaz, Jorge; Quintana, Gerardo

2009-03-01

In Colombia, the cost burden of chronic diseases is not well known, either globally or in localized areas of the health system. Rheumatoid arthritis is one of most common chronic diseases, and represents a high cost for the health system. The direct medical costs were estimated for rheumatoid arthritis patients in the in the first year of diagnosis at a level 3 university hospital in Colombia. Three therapy settings for early rheumatoid arthritis patients were established in the first year of diagnosis according to national and international guidelines. Each setting included treatment with disease-modifying anti-rheumatic drugs or biologic therapy based on disease severity as measured by Disease Activity Score 28. All direct medical costs were included: specialized medical care, diagnostic tests and drugs. Cost information was obtained from the Central Military Hospital finance department in Bogotá and the national manual of drug prices based on the "Farmaprecios" 2007 guide, a reference in general use by health institutions. Results. The average of cost of medical care in patients with mild, moderate and severe disease was US $1689, $1805 and $23,441 respectively. The recommended retail prices of the medicines published in "Farmaprecios" was US $1418, $1821 and $31,931. When the charges levied by several major health institutions were compared, substantial increases were noted, US $4936, $7716 and $123,661, respectively. Drug costs represented 86% of total cost, laboratory costs were 10% and medical attention was only 4%. Drugs costs were the principal component of the total direct medical cost, and it increased 40 times when a biological therapy is used. Complete economic evaluation studies are necesary to estimate the viability and clinical relevance of biological therapy for early rheumatoid arthritis.

The Psychometric Properties of the Voice Handicap Index in People With Parkinson's Disease.

PubMed

Guimaraes, I; Cardoso, R; Pinto, S; Ferreira, J J

2017-03-01

Psychosocial impact of dysphonia in people with Parkinson disease (PD) has been described with the Voice Handicap Index (VHI); however, its psychometric properties when applied in this population are not described. The objective of this study was to examine the psychometric properties of the VHI in people with PD. A cross-sectional study of 151 subjects without cognitive impairment (90 people with PD and 61 controls) was carried out. The VHI was applied along with clinician-based (Mini Mental State Examination, Hoehn and Yahr staging, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale) and patient-based (self-rated voice severity) outcome measures. The psychometric properties of the VHI analyzed were the feasibility, reliability, and construct validity. The average age of the PD population studied was 67 years; 51% had a primary level of education and 81% were retired. On average, they had disease onset duration of 11 years, a mild disease stage, mild to moderate global motor disability and impairment, and a normal to mild self-rated voice severity. The psychometric attributes of the VHI demonstrated that the questionnaire is feasible (missing data less than 1%), reliable (Cronbach α > 0.9), and valid (71.5% of the total variance is explained by five factors, correlates with voice severity, PD disability, and impairment, and differentiates subjects with PD from subjects without PD). The VHI is a reliable and valid tool that can be recommended for the population under study although further work is required to investigate its utility in advanced stages of disease. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

PubMed

López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular pathway involved in the development of ICAD from its asymptomatic stage.

[Homeostasis and Disorder of Musculoskeletal System.Diagnosis and Treatment of Congenital Musculoskeletal Diseases.

PubMed

Michigami, Toshimi

Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-β and chemical chaperones can be beneficial. Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has been recently developed to treat hypophosphatasia and has much improved the prognosis of the patients affected with severe forms of the disease. To treat the severe short stature in achondroplasia, drugs targeting the fibroblast growth factor receptor 3(FGFR3)-mediated signal are in development for clinical use.

Precision medicine in myasthenia graves: begin from the data precision

PubMed Central

Hong, Yu; Xie, Yanchen; Hao, Hong-Jun; Sun, Ren-Cheng

2016-01-01

Myasthenia gravis (MG) is a prototypic autoimmune disease with overt clinical and immunological heterogeneity. The data of MG is far from individually precise now, partially due to the rarity and heterogeneity of this disease. In this review, we provide the basic insights of MG data precision, including onset age, presenting symptoms, generalization, thymus status, pathogenic autoantibodies, muscle involvement, severity and response to treatment based on references and our previous studies. Subgroups and quantitative traits of MG are discussed in the sense of data precision. The role of disease registries and scientific bases of precise analysis are also discussed to ensure better collection and analysis of MG data. PMID:27127759

Progressive Impairment of Lactate-based Gluconeogenesis in the Huntington's Disease Mouse Model R6/2.

PubMed

Nielsen, Signe Marie Borch; Hasholt, Lis; Nørremølle, Anne; Josefsen, Knud

2015-04-20

Huntington's disease (HD) is a neurodegenerative illness, where selective neuronal loss in the brain caused by expression of mutant huntingtin protein leads to motor dysfunction and cognitive decline in addition to peripheral metabolic changes. In this study we confirm our previous observation of impairment of lactate-based hepatic gluconeogenesis in the transgenic HD mouse model R6/2 and determine that the defect manifests very early and progresses in severity with disease development, indicating a potential to explore this defect in a biomarker context. Moreover, R6/2 animals displayed lower blood glucose levels during prolonged fasting compared to wild type animals.

A diagnostic approach to hemochromatosis

PubMed Central

Tavill, Anthony S; Adams, Paul C

2006-01-01

In the present clinical review, a diagnostic approach to hemochromatosis is discussed from the perspective of two clinicians with extensive experience in this area. The introduction of genetic testing and large-scale population screening studies have broadened our understanding of the clinical expression of disease and the utility of biochemical iron tests for the detection of disease and for the assessment of disease severity. Liver biopsy has become more of a prognostic test than a diagnostic test. The authors offer a stepwise, diagnostic algorithm based on current evidence-based data, that they regard as most cost-effective. An early diagnosis can lead to phlebotomy therapy to prevent the development of cirrhosis. PMID:16955151

Diagnostic criteria, severity classification and guidelines of localized scleroderma.

PubMed

Asano, Yoshihide; Fujimoto, Manabu; Ishikawa, Osamu; Sato, Shinichi; Jinnin, Masatoshi; Takehara, Kazuhiko; Hasegawa, Minoru; Yamamoto, Toshiyuki; Ihn, Hironobu

2018-04-23

We established diagnostic criteria and severity classification of localized scleroderma because there is no established diagnostic criteria or widely accepted severity classification of the disease. Also, there has been no clinical guideline for localized scleroderma, so we established its clinical guideline ahead of all over the world. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of localized scleroderma. © 2018 Japanese Dermatological Association.

Challenges and opportunities for pediatric severe TBI-review of the evidence and exploring a way forward.

PubMed

Bell, Michael J; Adelson, P David; Wisniewski, Stephen R

2017-10-01

Traumatic brain injury (TBI) is a leading killer of children in the developed and developing world. Despite evidence-based guidelines and several recent clinical trials, the progress in developing best practices for children with severe TBI has been slow. This article describes (i) the burden of the disease, (ii) the inadequacies of the evidence-based guidelines, (iii) the failure of the largest clinical trials to prove their primary hypotheses, and (iv) possible advances from an observational cohort study called the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial that has recently completed enrollment.

A discussion on disease severity index values: using the disease severity index for null hypothesis testing

USDA-ARS?s Scientific Manuscript database

A disease severity index (DSI) is a single number for summarizing a large amount of information on disease severity. It has been used to indicate the performance of a cultivar in regard to disease resistance at a particular location, to relate disease severity to yield loss, to determine the effecti...

Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

PubMed

Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo

2017-03-01

The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Orphan Disease Networks

PubMed Central

Zhang, Minlu; Zhu, Cheng; Jacomy, Alexis; Lu, Long J.; Jegga, Anil G.

2011-01-01

The low prevalence rate of orphan diseases (OD) requires special combined efforts to improve diagnosis, prevention, and discovery of novel therapeutic strategies. To identify and investigate relationships based on shared genes or shared functional features, we have conducted a bioinformatic-based global analysis of all orphan diseases with known disease-causing mutant genes. Starting with a bipartite network of known OD and OD-causing mutant genes and using the human protein interactome, we first construct and topologically analyze three networks: the orphan disease network, the orphan disease-causing mutant gene network, and the orphan disease-causing mutant gene interactome. Our results demonstrate that in contrast to the common disease-causing mutant genes that are predominantly nonessential, a majority of orphan disease-causing mutant genes are essential. In confirmation of this finding, we found that OD-causing mutant genes are topologically important in the protein interactome and are ubiquitously expressed. Additionally, functional enrichment analysis of those genes in which mutations cause ODs shows that a majority result in premature death or are lethal in the orthologous mouse gene knockout models. To address the limitations of traditional gene-based disease networks, we also construct and analyze OD networks on the basis of shared enriched features (biological processes, cellular components, pathways, phenotypes, and literature citations). Analyzing these functionally-linked OD networks, we identified several additional OD-OD relations that are both phenotypically similar and phenotypically diverse. Surprisingly, we observed that the wiring of the gene-based and other feature-based OD networks are largely different; this suggests that the relationship between ODs cannot be fully captured by the gene-based network alone. PMID:21664998

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

Data-Driven Sequence of Changes to Anatomical Brain Connectivity in Sporadic Alzheimer's Disease.

PubMed

Oxtoby, Neil P; Garbarino, Sara; Firth, Nicholas C; Warren, Jason D; Schott, Jonathan M; Alexander, Daniel C

2017-01-01

Model-based investigations of transneuronal spreading mechanisms in neurodegenerative diseases relate the pattern of pathology severity to the brain's connectivity matrix, which reveals information about how pathology propagates through the connectivity network. Such network models typically use networks based on functional or structural connectivity in young and healthy individuals, and only end-stage patterns of pathology, thereby ignoring/excluding the effects of normal aging and disease progression. Here, we examine the sequence of changes in the elderly brain's anatomical connectivity over the course of a neurodegenerative disease. We do this in a data-driven manner that is not dependent upon clinical disease stage, by using event-based disease progression modeling. Using data from the Alzheimer's Disease Neuroimaging Initiative dataset, we sequence the progressive decline of anatomical connectivity, as quantified by graph-theory metrics, in the Alzheimer's disease brain. Ours is the first single model to contribute to understanding all three of the nature, the location, and the sequence of changes to anatomical connectivity in the human brain due to Alzheimer's disease. Our experimental results reveal new insights into Alzheimer's disease: that degeneration of anatomical connectivity in the brain may be a viable, even early, biomarker and should be considered when studying such neurodegenerative diseases.

A retrospective study of clinical signs and epidemiology of chronic valve disease in a group of 207 Dachshunds in Poland

PubMed Central

2013-01-01

Background Chronic mitral valve disease is frequently seen in the Dachshund. Dachshunds (n=207) made up 11.73% of the dogs admitted to the Cardiology Service at the Small Animal Clinic, Warsaw University of Life Sciences, Poland (first visits only). Results Of these, 35 dogs had no clinically detectable heart disease while 172 had chronic valve disease with the mitral valve affected most often (130 dogs), both mitral and tricuspid valves infrequently (39 dogs) and rarely the tricuspid valve (3 dogs). Males were affected more frequently than females and the average age of dogs with chronic valve disease was 11.9 years for females and 11.3 years for males. A majority of the diseased Dachshunds were classified as ISACHC 2 (79), followed by ISACHC 1 (60). Most frequent clinical signs noted by owners included coughing, exercise intolerance, dyspnea and tachypnea. Heart murmurs were generally louder with increased disease severity; however there were 20 dogs in the ISACHC 1 group with no audible heart murmurs. The most frequent electrocardiographic abnormalities included an increased P wave and QRS complex duration, increased R wave amplitude and tachycardia. With increased disease severity, echocardiography revealed an increase in heart size. A higher ISACHC class was related to increased heart size (based on echocardiography) and increased percentage of patients exhibiting enlargement of both left atrium and left ventricle (based on radiography). Conclusions The Dachshund is often affected by chronic mitral valvular disease with a late onset of associated clinical signs and few cardiac complications. PMID:23844824

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.

Celiac Disease and Concomitant Conditions: A Case-based Review.

PubMed

Lodhi, Muhammad Uzair; Stammann, Tracy; Kuzel, Aaron R; Syed, Intekhab Askari; Ishtiaq, Rizwan; Rahim, Mustafa

2018-02-02

Celiac disease is a chronic autoimmune disease with genetic predisposition, triggered by the ingestion of gluten. It has a wide range of clinical manifestations ranging from asymptomatic forms to classic presentation of malabsorption with diarrhea and abdominal cramps. Celiac disease can also present with several other concomitant disorders (at the time of diagnosis or during the course of celiac disease) such as: type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, thyroid disorders, nutritional deficiencies, and gram-negative sepsis. We present a 57-year-old female with past medical history of rheumatoid arthritis, who presented to the emergency department with a complaint of chronic diarrhea, complicated by gram-negative sepsis. The family history of the patient was significant for celiac disease, type 1 diabetes, and rheumatoid arthritis. The patient was closely monitored and treated appropriately. In this case-based review, we explore different associated conditions of celiac disease in the literature, as well as the patient's risk of developing malignancy.

Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

PubMed

Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

2016-01-01

Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.

Predicting drug-disease interactions by semi-supervised graph cut algorithm and three-layer data integration.

PubMed

Wu, Guangsheng; Liu, Juan; Wang, Caihua

2017-12-28

Prediction of drug-disease interactions is promising for either drug repositioning or disease treatment fields. The discovery of novel drug-disease interactions, on one hand can help to find novel indictions for the approved drugs; on the other hand can provide new therapeutic approaches for the diseases. Recently, computational methods for finding drug-disease interactions have attracted lots of attention because of their far more higher efficiency and lower cost than the traditional wet experiment methods. However, they still face several challenges, such as the organization of the heterogeneous data, the performance of the model, and so on. In this work, we present to hierarchically integrate the heterogeneous data into three layers. The drug-drug and disease-disease similarities are first calculated separately in each layer, and then the similarities from three layers are linearly fused into comprehensive drug similarities and disease similarities, which can then be used to measure the similarities between two drug-disease pairs. We construct a novel weighted drug-disease pair network, where a node is a drug-disease pair with known or unknown treatment relation, an edge represents the node-node relation which is weighted with the similarity score between two pairs. Now that similar drug-disease pairs are supposed to show similar treatment patterns, we can find the optimal graph cut of the network. The drug-disease pair with unknown relation can then be considered to have similar treatment relation with that within the same cut. Therefore, we develop a semi-supervised graph cut algorithm, SSGC, to find the optimal graph cut, based on which we can identify the potential drug-disease treatment interactions. By comparing with three representative network-based methods, SSGC achieves the highest performances, in terms of both AUC score and the identification rates of true drug-disease pairs. The experiments with different integration strategies also demonstrate that considering several sources of data can improve the performances of the predictors. Further case studies on four diseases, the top-ranked drug-disease associations have been confirmed by KEGG, CTD database and the literature, illustrating the usefulness of SSGC. The proposed comprehensive similarity scores from multi-views and multiple layers and the graph-cut based algorithm can greatly improve the prediction performances of drug-disease associations.

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

PubMed Central

Ravichandran, Srikanth; Michelucci, Alessandro; del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases. PMID:29551980

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease.

PubMed

Ravichandran, Srikanth; Michelucci, Alessandro; Del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases.

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

Update of the Case Definitions for Population-Based Surveillance of Periodontitis

PubMed Central

Eke, Paul I.; Page, Roy C.; Wei, Liang; Thornton-Evans, Gina; Genco, Robert J.

2018-01-01

Background This report adds a new definition for mild periodontitis that allows for better descriptions of the overall prevalence of periodontitis in populations. In 2007, the Centers for Disease Control and Prevention in partnership with the American Academy of Periodontology developed and reported standard case definitions for surveillance of moderate and severe periodontitis based on measurements of probing depth (PD) and clinical attachment loss (AL) at interproximal sites. However, combined cases of moderate and severe periodontitis are insufficient to determine the total prevalence of periodontitis in populations. Methods The authors proposed a definition for mild periodontitis as ≥2 interproximal sites with AL ≥3 mm and ≥2 interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. The effect of the proposed definition on the total burden of periodontitis was assessed in a convenience sample of 456 adults ≥35 years old and compared with other previously reported definitions for similar categories of periodontitis. Results Addition of mild periodontitis increases the total prevalence of periodontitis by ≈31% in this sample when compared with the prevalence of severe and moderate disease. Conclusion Total periodontitis using the case definitions in this study should be based on the sum of mild, moderate, and severe periodontitis. PMID:22420873

[Prevalence of severe periodontal disease and its association with respiratory disease in hospitalized adult patients in a tertiary care center].

PubMed

Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; García-Sancho, Cecilia; Franco-Marina, Francisco; González-Cruz, Herminia

2015-01-01

Severe periodontal disease is a chronic inflammatory gingival process associated with systemic diseases. To determine the prevalence of severe periodontal disease and its association with respiratory diseases among hospitalized patients at the Institute of Respiratory Diseases "Ismael Cosio Villegas" (INER) in 2011. A cross-sectional study was developed. The severe periodontal disease was diagnosed by the Department of Stomatology. The International Classification of Diseases 10th revision was used. A multinomial logistic was fit to estimate relative-risk. Three thousand and fifty-nine patients were included; 772/3,059 (25.2%) had severe periodontal disease. After controlling for age, sex, inpatient days, death, and socioeconomic status, the infectious respiratory diseases that were significantly associated with severe periodontal disease were: HIV/AIDS (RR: 10.6; 95% CI: 9.1-23.3; p < 0.0001); pneumonia (RR: 2.6; 95% CI: 2.2-5.7; p < 0.0001); pulmonary tuberculosis and its sequels (RR: 2.1; 95% CI: 1.6-4.9; p < 0.0001); and lung abscess (RR: 2.6; 95% CI: 1.6-7.8; p = 0.002). Lung cancer and pleural diseases were also significantly associated with severe periodontal disease. High prevalence of severe periodontal disease was observed in the different respiratory diseases. Severe periodontal disease was associated with both infectious and non-infectious respiratory diseases. It is important to study an oral health intervention.

A Distributed Platform for Global-Scale Agent-Based Models of Disease Transmission

PubMed Central

Parker, Jon; Epstein, Joshua M.

2013-01-01

The Global-Scale Agent Model (GSAM) is presented. The GSAM is a high-performance distributed platform for agent-based epidemic modeling capable of simulating a disease outbreak in a population of several billion agents. It is unprecedented in its scale, its speed, and its use of Java. Solutions to multiple challenges inherent in distributing massive agent-based models are presented. Communication, synchronization, and memory usage are among the topics covered in detail. The memory usage discussion is Java specific. However, the communication and synchronization discussions apply broadly. We provide benchmarks illustrating the GSAM’s speed and scalability. PMID:24465120

Evaluation of nutritional indicators and body composition in patients with advanced liver disease enrolled for liver transplantation.

PubMed

Vulcano, Daniela Salate Biagioni; Carvalhaes, Maria Antonieta de Barros Leite; Bakonyi Neto, Alexandre

2013-10-01

Malnutrition is prevalent in patients with advanced liver disease (LD) related to multifactorial causes. Fluid retention can underestimate the nutritional status based on anthropometric measures. We evaluated nutritional indicators and body composition (BC) in patients with liver cirrhosis and correlated them with LD severity. Forty three patients with LD enrolled for liver transplantation were evaluated by Anthropometric measures, subjective evaluation (Global Assessment of Nutritional Status - SGA) and biochemical indicators. Single-frequency electrical bioimpedance (SFE-BIA) was used to evaluate body composition (BC). It measured resistance (R), reactance (Xc) and the phase angle (PA). LD severity was estimated by Child-Pugh and Meld criteria (Model for End-Stage Liver Disease). Child-Pugh index between patients was 7.11 ± 1.70 and Meld was 12.23 ± 4.22. Arm Circumference, Arm Muscle Circumference and Arm Muscle Area, SGA, hemoglobin, hematocrit and albumin showed better correlation with disease severity. Xc and PA showed correlation both with Meld and Child-Pugh score when BC were evaluated. PA was depleted in 55.8% of the patients. Diagnosis of malnutrition varied according to the method. Global assessment of nutritional status showed better correlation with disease severity than with objective methods. Single-frequency electrical bioimpedance for body composition analysis in cirrhotic patients must be cautiously used; however, primary vectors seems to be valid and promising in clinical practice.

[Application of iodine metabolism analysis methods in thyroid diseases].

PubMed

Han, Jian-hua; Qiu, Ling

2013-08-01

The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

[CHRONIC PERIODONTITIS WITH SYMPTOMATIC HYPERTROPHIC GINGIVITIS: CASE REPORT AND REVIEW OF THE LITERATURE].

PubMed

Shinkevich, V; Udaltsova, K; Pisarenko, E; Kolomiets, S; Khmil, T

2015-12-01

Gingivitis in traditional national dentistry referred to independent diseases or symptomatic condition in periodontitis and classified morphologically. The diagnostic features of the diseases are characteristic, but the clinical presentation of symptomatic gingivitis and patterns of bone destructions may vary between patients. Successful treatment of the disease depends from proper diagnosis and advanced disease stages, but for symptomatic gingivitis that accompanying chronic periodontitis, protocols include surgical excision. Despite of the high prevalence of chronic generalized periodontitis, its active treatment often start in severe destruction and bone loss (2-3 stage severity). Today etiotropic antimicrobial therapy is real way to control microbial biofilm and has solid evidence base. Applying of etiotropic antimicrobial therapy as systemic azithromycin with timely treatment of mild to moderate periodontal and bone destruction may reduce severe periodontitis incidence of and treatment-related complications in the future. This paper attempts to describe the clinical diagnostic features and the current treatment options along with a suggested protocol for comprehensive management of chronic generalized periodontitis and hypertrophic gingivitis patient with case reports and a brief review.

Localized scleroderma.

PubMed

Kreuter, Alexander

2012-01-01

Localized scleroderma (also called morphea) is a term encompassing a spectrum of sclerotic autoimmune diseases that primarily affect the skin, but also might involve underlying structures such as the fat, fascia, muscle, and bones. Its exact pathogenesis is still unknown, but several trigger factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis. To date, there are no specific serological markers available for localized scleroderma. Within the last years, several validated clinical scores have been introduced as potential outcome measures for the disease. Given the rarity of localized scleroderma, only few evidence-based therapeutical treatment options exist. So far, the most robust data is available for ultraviolet A1 phototherapy in disease that is restricted to the skin, and methotrexate alone or in combination with systemic corticosteroids in more severe disease that additionally affects extracutaneous structures. This practical review summarizes relevant information on the epidemiology, pathogenesis, clinical subtypes and classifications, differential diagnoses, clinical scores and outcome measures, and current treatment strategies of localized scleroderma. © 2012 Wiley Periodicals, Inc.

What predicts depression in cardiac patients: sociodemographic factors, disease severity or theoretical vulnerabilities?

PubMed

Doyle, F; McGee, H M; Conroy, R M; Delaney, M

2011-05-01

Depression is associated with increased cardiovascular risk in acute coronary syndrome (ACS) patients, but some argue that elevated depression is actually a marker of cardiovascular disease severity. Therefore, disease indices should better predict depression than established theoretical causes of depression (interpersonal life events, reinforcing events, cognitive distortions, type D personality). However, little theory-based research has been conducted in this area. In a cross-sectional design, ACS patients (n = 336) completed questionnaires assessing depression and psychosocial vulnerabilities. Nested logistic regression assessed the relative contribution of demographic or vulnerability factors, or disease indices or vulnerabilities to depression. In multivariate analysis, all vulnerabilities were independent significant predictors of depression (scoring above threshold on any scale, 48%). Demographic variables accounted for <1% of the variance of depression status, with vulnerabilities accounting for significantly more (pseudo R² = 0.16, χ²(change) = 150.9, df = 4, p < 0.001). Disease indices accounted for 7% of the variance in depression (pseudo R² = 0.07, χ² = 137.9, p < 0.001). However, adding the vulnerabilities increased the overall variance explained to 22% (pseudo R² = 0.22, χ² = 58.6, df = 4, p < 0.001). Theoretical vulnerabilities predicted depression status better than did either demographic or disease indices. The presence of these proximal causes of depression suggests that depression in ACS patients is not simply a result of cardiovascular disease severity.

Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4): An Emerging Biomarker for Skin Inflammatory Diseases.

PubMed

Izuhara, Kenji; Yamaguchi, Yukie; Ohta, Shoichiro; Nunomura, Satoshi; Nanri, Yasuhiro; Azuma, Yoshinori; Nomura, Noriko; Noguchi, Yasuhiko; Aihara, Michiko

2018-04-06

Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various kinds of squamous cell carcinomas. Recently, our understanding of the underlying mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover, it has been shown that SCCA1/2 are involved in the pathogenesis of several inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD). IL-22 and IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13, signature cytokines of type 2 inflammation, both of which are positively correlated with the pathogenesis of psoriasis and allergic diseases, respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or keratinocytes, leading to high expression of SCCA1/2 in these diseases. Based on these findings, several trials have been performed to examine the potential of applying SCCA1/2 to biomarkers for these diseases. The findings show that SCCA2 is useful to aid diagnosis, estimate clinical severity and disease type, and assess responses to treatment in psoriasis and AD. These results suggest that SCCA2 has emerged as a novel biomarker for skin inflammatory diseases.

An epidemiological perspective of personalized medicine: the Estonian experience

PubMed Central

Milani, L; Leitsalu, L; Metspalu, A

2015-01-01

Milani L, Leitsalu L, Metspalu A (University of Tartu). An epidemiological perspective of personalized medicine: the Estonian experience (Review). J Intern Med 2015; 277: 188–200. The Estonian Biobank and several other biobanks established over a decade ago are now starting to yield valuable longitudinal follow-up data for large numbers of individuals. These samples have been used in hundreds of different genome-wide association studies, resulting in the identification of reliable disease-associated variants. The focus of genomic research has started to shift from identifying genetic and nongenetic risk factors associated with common complex diseases to understanding the underlying mechanisms of the diseases and suggesting novel targets for therapy. However, translation of findings from genomic research into medical practice is still lagging, mainly due to insufficient evidence of clinical validity and utility. In this review, we examine the different elements required for the implementation of personalized medicine based on genomic information. First, biobanks and genome centres are required and have been established for the high-throughput genomic screening of large numbers of samples. Secondly, the combination of susceptibility alleles into polygenic risk scores has improved risk prediction of cardiovascular disease, breast cancer and several other diseases. Finally, national health information systems are being developed internationally, to combine data from electronic medical records from different sources, and also to gradually incorporate genomic information. We focus on the experience in Estonia, one of several countries with national goals towards more personalized health care based on genomic information, where the unique combination of elements required to accomplish this goal are already in place. PMID:25339628

Rheumatic manifestations of hepatitis C virus chronic infection: Indications for a correct diagnosis.

PubMed

Palazzi, Carlo; D'Amico, Emilio; D'Angelo, Salvatore; Gilio, Michele; Olivieri, Ignazio

2016-01-28

Hepatitis C virus (HCV) is a hepato- and lymphotropic agent that is able to induce several autoimmune rheumatic disorders: vasculitis, sicca syndrome, arthralgias/arthritis and fibromyalgia. The severity of clinical manifestations is variable and sometimes life-threatening. HCV infection can mimic many primitive rheumatic diseases, therefore, it is mandatory to distinguish HCV-related manifestations from primitive ones because the prognosis and therapeutic strategies can be fairly dissimilar. The new direct-acting antivirals drugs can help to avoid the well-known risks of worsening or new onset of autoimmune diseases during the traditional interferon-based therapies.

The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere.

PubMed

Murray, K O; Walker, C; Gould, E

2011-06-01

West Nile virus (WNV) is now endemic in the USA. After the widespread surge of virus activity across the USA, research has flourished, and our knowledge base has significantly expanded over the past 10 years since WNV was first recognized in New York City. This article provides a review of the virology of WNV, history, epidemiology, clinical features, pathology of infection, the innate and adaptive immune response, host risk factors for developing severe disease, clinical sequelae following severe disease, chronic infection, and the future of prevention.

Estimation of the National Disease Burden of Influenza-Associated Severe Acute Respiratory Illness in Kenya and Guatemala: A Novel Methodology

PubMed Central

Katz, Mark A.; Lindblade, Kim A.; Njuguna, Henry; Arvelo, Wences; Khagayi, Sammy; Emukule, Gideon; Linares-Perez, Nivaldo; McCracken, John; Nokes, D. James; Ngama, Mwanajuma; Kazungu, Sidi; Mott, Joshua A.; Olsen, Sonja J.; Widdowson, Marc-Alain; Feikin, Daniel R.

2013-01-01

Background Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries. PMID:23573177

SARS Grid--an AG-based disease management and collaborative platform.

PubMed

Hung, Shu-Hui; Hung, Tsung-Chieh; Juang, Jer-Nan

2006-01-01

This paper describes the development of the NCHC's Severe Acute Respiratory Syndrome (SARS) Grid project-An Access Grid (AG)-based disease management and collaborative platform that allowed for SARS patient's medical data to be dynamically shared and discussed between hospitals and doctors using AG's video teleconferencing (VTC) capabilities. During the height of the SARS epidemic in Asia, SARS Grid and the SARShope website significantly curved the spread of SARS by helping doctors manage the in-hospital and in-home care of quarantined SARS patients through medical data exchange and the monitoring of the patient's symptoms. Now that the SARS epidemic has ended, the primary function of the SARS Grid project is that of a web-based informatics tool to increase pubic awareness of SARS and other epidemic diseases. Additionally, the SARS Grid project can be viewed and further studied as an outstanding model of epidemic disease prevention and/or containment.

Comparing ESC and iPSC-Based Models for Human Genetic Disorders.

PubMed

Halevy, Tomer; Urbach, Achia

2014-10-24

Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients' somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn't be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.

Association of Polysensitization, Allergic Multimorbidity, and Allergy Severity: A Cross-Sectional Study of School Children.

PubMed

Ha, Eun Kyo; Baek, Ji Hyeon; Lee, So-Yeon; Park, Yong Mean; Kim, Woo Kyung; Sheen, Youn Ho; Lee, Seung Jin; Bae, Youngoh; Kim, Jihyeon; Lee, Kee-Jae; Ahn, Kangmo; Kwon, Ho-Jang; Han, Man Yong

2016-01-01

Aeroallergen sensitization is related to the coexistence of allergic diseases, but the nature of this relationship is poorly understood. The aim of this study was to clarify the relationship of polysensitization with allergic multimorbidities and the severity of allergic diseases. This study is a cross-sectional analysis of 3,368 Korean children aged 6-7 years-old. We defined IgE-mediated allergic diseases based on structured questionnaires, and classified the sensitivity to 18 aeroallergens by logistic regression and the Ward hierarchical clustering method. The relationship of polysensitization (positive IgE responses against 2 or more aeroallergens classes) with allergic multimorbidities (coexistence of 2 or more of the following allergic diseases: asthma, rhinitis, eczema, and conjunctivitis) and severity of allergic diseases was determined by ordinal logistic regression analysis. The rate of polysensitization was 13.6% (n = 458, 95% CI 12.4-14.8) and that of allergic multimorbidity was 23.5% (n = 790, 95% CI 22.0-24.9). Children sensitized to more aeroallergens tended to have more allergic diseases (rho = 0.248, p < 0.001), although the agreement between polysensitization and multimorbidity was poor (kappa = 0.11, p < 0.001). The number allergen classes to which a child was sensitized increased the risk of wheezing attacks (1 allergen: adjusted odds ratio [aOR] 2.22, 4 or more allergens: aOR 9.39), absence from school (1 allergen: aOR 1.96, 3 allergens: aOR 2.08), and severity of nasal symptoms (1 allergen: aOR 1.61, 4 or more allergens: aOR 4.38). Polysensitization was weakly related to multimorbidity. However, the number of allergens to which a child is sensitized is related to the severity of IgE-mediated symptoms. © 2017 S. Karger AG, Basel.

Biomarkers in Pediatric Community-Acquired Pneumonia.

PubMed

Principi, Nicola; Esposito, Susanna

2017-02-19

Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended.

Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics.

PubMed

Hatakeyama, Hideyuki; Goto, Yu-Ichi

2016-04-01

Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics. © 2016 AlphaMed Press.

Tocilizumab: therapy and safety management.

PubMed

Pham, Thao; Claudepierre, Pascal; Constantin, Arnaud; de Bandt, Michel; Fautrel, Bruno; Gossec, Laure; Gottenberg, Jacques-Eric; Goupille, Philippe; Guillaume, Séverine; Hachulla, Eric; Masson, Charles; Morel, Jacques; Puéchal, Xavier; Saraux, Alain; Schaeverbeke, Thierry; Wendling, Daniel; Bruckert, Eric; Pol, Stanislas; Mariette, Xavier; Sibilia, Jean

2010-06-01

To develop fact sheets about tocilizumab, in order to assist physicians in the management of patients with inflammatory joint disease. 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable; 2. identification and review of publications relevant to each topic; 3. development of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The 20 experts were rheumatologists and invited specialists in other fields, and they had extensive experience with the management of RA. They were members of the CRI (Club Rhumatismes et Inflammation), a section of the Société Francaise de Rhumatologie. Each fact sheet was revised by several. experts and the overall process was coordinated by three experts. Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: Several topics of major interest were selected: contraindications of tocilizumab; the management of adverse effects and concomitant diseases that may develop during tocilizumab therapy; and the management of everyday situations such as pregnancy, surgery, and immunizations. After a review of the literature and discussions among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of tocilizumab therapy, management of patients with specific past histories, and specific clinical situations such as pregnancy; 2. diseases other than RA, such as juvenile idiopathic arthritis; 3. models of letters for informing the rheumatologist and general practitioner; 4. and patient information. These tocilizumab fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on tocilizumab therapy. They will be available continuously at www.cri-net.com and updated at appropriate intervals. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Periodontal Disease and Tooth Loss as Risks for Cancer: A Systematic Review of the Literature

PubMed Central

Sadighi Shamami, M; Sadighi Shamami, M; Amini, S

2011-01-01

Background Periodontal disease is a chronic destructive disease which occurs in adults, young people, and children. Periodontal disease and periodontal pathogens have been associated with several systemic diseases and more recently, several studies have suggested the relationship between periodontal disease and cancer. Studies with adjustment for the effect of smoking exposure, have found significant positive associations with different cancer sites. This review has outlined recent epidemiologic researches pointing to a possible role for tooth loss and periodontal disease in carcinogenesis. Methods In this review, articles were selected from PubMed between1995 and June 2010 including human. Amongst 5,984 articles identified from the electronic search, 17 articles were selected for a full-text reading based on the inclusion and the exclusion criteria. Results Nine out of 10 case-control studies reported a significant increase in the risk of oral cancer in patients with periodontitis and one with no significant association. Among 6 studies examining esophageal cancer and periodontal disease, 5 studies found a significant association between them and one study failed to find a significant increased risk of cancer. Also amongst 5 studies which focused on upper gastrointestinal, gastric cancer, and periodontal disease, 4 studies found an increased risk of cancer while one study did not report any relationship. In lung cancer evaluations, 3 out of 4 studies showed some levels of association between lung cancer and periodontal disease but after adjustment for smoking, no relationship were found. Three cohort studies have evaluated overall cancer rates in periodontal patients; two of them found small but significant association between cancers and periodontal disease. Conclusion The results indicate that there is a possible link between cancer and severe periodontal disease after adjustment for smoking and drinking habits. PMID:26322197

Periodontal Disease and Tooth Loss as Risks for Cancer: A Systematic Review of the Literature.

PubMed

Sadighi Shamami, M; Sadighi Shamami, M; Amini, S

2011-01-01

Periodontal disease is a chronic destructive disease which occurs in adults, young people, and children. Periodontal disease and periodontal pathogens have been associated with several systemic diseases and more recently, several studies have suggested the relationship between periodontal disease and cancer. Studies with adjustment for the effect of smoking exposure, have found significant positive associations with different cancer sites. This review has outlined recent epidemiologic researches pointing to a possible role for tooth loss and periodontal disease in carcinogenesis. In this review, articles were selected from PubMed between1995 and June 2010 including human. Amongst 5,984 articles identified from the electronic search, 17 articles were selected for a full-text reading based on the inclusion and the exclusion criteria. Nine out of 10 case-control studies reported a significant increase in the risk of oral cancer in patients with periodontitis and one with no significant association. Among 6 studies examining esophageal cancer and periodontal disease, 5 studies found a significant association between them and one study failed to find a significant increased risk of cancer. Also amongst 5 studies which focused on upper gastrointestinal, gastric cancer, and periodontal disease, 4 studies found an increased risk of cancer while one study did not report any relationship. In lung cancer evaluations, 3 out of 4 studies showed some levels of association between lung cancer and periodontal disease but after adjustment for smoking, no relationship were found. Three cohort studies have evaluated overall cancer rates in periodontal patients; two of them found small but significant association between cancers and periodontal disease. The results indicate that there is a possible link between cancer and severe periodontal disease after adjustment for smoking and drinking habits.

Abatacept therapy and safety management.

PubMed

Pham, Thao; Bachelez, Hervé; Berthelot, Jean-Marie; Blacher, Jacques; Claudepierre, Pascal; Constantin, Arnaud; Fautrel, Bruno; Gaujoux-Viala, Cécile; Goëb, Vincent; Gossec, Laure; Goupille, Philippe; Guillaume-Czitrom, Séverine; Hachulla, Eric; Lequerré, Thierry; Marolleau, Jean-Pierre; Martinez, Valérie; Masson, Charles; Mouthon, Luc; Puéchal, Xavier; Richette, Pascal; Saraux, Alain; Schaeverbeke, Thierry; Soubrier, Martin; Viguier, Manuelle; Vittecoq, Olivier; Wendling, Daniel; Mariette, Xavier; Sibilia, Jean

2012-03-01

To develop and/or update fact sheets about abatacept treatment, in order to assist physicians in the management of patients with inflammatory joint disease. 1. selection by a committee of rheumatology experts of the main topics of interest for which fact sheets were desirable 2. identification and review of publications relevant to each topic 3. development and/or update of fact sheets based on three levels of evidence: evidence-based medicine, official recommendations, and expert opinion. The experts were rheumatologists and invited specialists in other fields (dermatologist, cardiologist, pediatric rheumatologist, endocrinologist, hematologist, immunologist, infectiologist), and they had extensive experience with the management of chronic inflammatory diseases, such as rheumatoid arthritis (RA). They were members of the CRI (Club Rhumatismes et Inflammation), a section of the French Rheumatology Society (Societe Francaise de Rhumatologie). Each fact sheet was revised by several experts and the overall process was coordinated by three experts. Several topics of major interest were selected: contraindications of abatacept treatment; management of adverse effects and concomitant diseases that may develop during abatacept treatment; and management of common situations such as pregnancy, surgery, patient older than 75 years of age, and patients with co-morbidities (such as dialysis, hemoglobinopathy, or splenectomy). After a review of the literature and discussion among experts, a consensus was developed about the content of the fact sheets presented here. These fact sheets focus on several points: 1. in RA, initiation and monitoring of the abatacept treatment, management of patients with specific past histories, and specific clinical situations such as pregnancy 2. diseases other than RA, such as juvenile idiopathic arthritis, spondylarthropathies, or autoimmune diseases (systemic lupus erythematosus and other systemic autoimmune diseases) 3. models of letters for informing the rheumatologist and general practitioner 4. patient information about the use of abatacept in RA 5. and data on the new abatacept formulation for subcutaneous administration (approved by the FDA in August 2011 for patients with moderate-to-severe RA). These fact sheets built on evidence-based medicine and expert opinion will serve as a practical tool for assisting physicians who manage patients on abatacept. They will be available continuously on www.cri-net.com and will be updated at appropriate intervals. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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.

Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

NASA Astrophysics Data System (ADS)

Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

2015-03-01

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

"Exercise as medicine" in chronic kidney disease.

PubMed

Wilkinson, T J; Shur, N F; Smith, A C

2016-08-01

Exercise and physical activity are increasingly becoming key tools in the treatment and prevention of several medical conditions including arthritis and diabetes; this notion has been termed "exercise as medicine". Exercise has favorable effects on reducing cardiovascular risk, inflammation, cachexia, and hypertension, in addition to increasing physical functioning, strength, and cardio-respiratory capacity. Chronic kidney disease, a condition that affects around 10% of the population, is often overlooked as a target for exercise-based therapy. Despite the vast range of severity in kidney disease (e.g., pre-dialysis, dialysis, transplant), exercise has a potential role in all patients suffering from the condition. In this review, we summarise the important role exercise may have in the clinical management of kidney disease and how this form of 'medicine' should be best administered and 'prescribed'. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment

PubMed Central

Germolec, Dori R.; Luebke, Robert W.; Johnson, Victor J.

2016-01-01

This overview is an update of the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. PMID:26828330

Biophysical Aspects of Alzheimer's Disease: Implications for Pharmaceutical Sciences : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

PubMed

Arosio, Paolo

2017-12-01

An increasing amount of findings suggests that the aggregation of soluble peptides and proteins into amyloid fibrils is a relevant upstream process in the complex cascade of events leading to the pathology of Alzheimer's disease and several other neurodegenerative disorders. Nevertheless, several aspects of the correlation between the aggregation process and the onset and development of the pathology remain largely elusive. In this context, biophysical and biochemical studies in test tubes have proven extremely powerful in providing quantitative information about the structure and the reactivity of amyloids at the molecular level. In this review we use selected recent examples to illustrate the importance of such biophysical research to complement phenomenological studies based on cellular and molecular biology, and we discuss the implications for pharmaceutical applications associated with Alzheimer's disease and other neurodegenerative disorders in both academic and industrial contexts.

Quantitative Pulmonary Imaging Using Computed Tomography and Magnetic Resonance Imaging

PubMed Central

Washko, George R.; Parraga, Grace; Coxson, Harvey O.

2011-01-01

Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic, and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review we will focus on two of them, x-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge. PMID:22142490

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment.

PubMed

DeWitt, Jamie C; Germolec, Dori R; Luebke, Robert W; Johnson, Victor J

2016-02-01

This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process. Copyright © 2016 John Wiley & Sons, Inc.

Neglected Parasitic Infections in the United States: Toxoplasmosis

PubMed Central

Jones, Jeffrey L.; Parise, Monica E.; Fiore, Anthony E.

2014-01-01

Toxoplasma gondii is a leading cause of severe foodborne illness in the United States. Population-based studies have found T. gondii infection to be more prevalent in racial/ethnic minority and socioeconomically disadvantaged groups. Soil contaminated with cat feces, undercooked meat, and congenital transmission are the principal sources of infection. Toxoplasmosis-associated illnesses include congenital neurologic and ocular disease; acquired illness in immunocompetent persons, most notably ocular disease; and encephalitis or disseminated disease in immunosuppressed persons. The association of T. gondii infection with risk for mental illness is intriguing and requires further research. Reduction of T. gondii in meat, improvements in hygiene and food preparation practices, and reduction of environmental contamination can prevent toxoplasmosis, but more research is needed on how to implement these measures. In addition, screening and treatment may help prevent toxoplasmosis or reduce the severity of disease in some settings. PMID:24808246

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Unravelling the Genetic Diversity among Cassava Bemisia tabaci Whiteflies Using NextRAD Sequencing.

PubMed

Wosula, Everlyne N; Chen, Wenbo; Fei, Zhangjun; Legg, James P

2017-11-01

Bemisia tabaci threatens production of cassava in Africa through vectoring viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD). B. tabaci sampled from cassava in eight countries in Africa were genotyped using NextRAD sequencing, and their phylogeny and population genetics were investigated using the resultant single nucleotide polymorphism (SNP) markers. SNP marker data and short sequences of mitochondrial DNA cytochrome oxidase I (mtCOI) obtained from the same insect were compared. Eight genetically distinct groups were identified based on mtCOI, whereas phylogenetic analysis using SNPs identified six major groups, which were further confirmed by PCA and multidimensional analyses. STRUCTURE analysis identified four ancestral B. tabaci populations that have contributed alleles to the six SNP-based groups. Significant gene flows were detected between several of the six SNP-based groups. Evidence of gene flow was strongest for SNP-based groups occurring in central Africa. Comparison of the mtCOI and SNP identities of sampled insects provided a strong indication that hybrid populations are emerging in parts of Africa recently affected by the severe CMD pandemic. This study reveals that mtCOI is not an effective marker at distinguishing cassava-colonizing B. tabaci haplogroups, and that more robust SNP-based multilocus markers should be developed. Significant gene flows between populations could lead to the emergence of haplogroups that might alter the dynamics of cassava virus spread and disease severity in Africa. Continuous monitoring of genetic compositions of whitefly populations should be an essential component in efforts to combat cassava viruses in Africa. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Identification of Weather Conditions Associated with the Occurrence, Severity, and Incidence of Black Seed Disease of Strawberry Caused by Mycosphaerella fragariae.

PubMed

Carisse, Odile; McNealis, Vanessa

2018-01-01

Black seed disease (BSD) of strawberry is a sporadic disease caused by Mycosphaerella fragariae. Because little is known about potential crop losses or the weather conditions conducive to disease development, fungicides are generally not applied or are applied based on a preset schedule. Data collected from 2000 to 2011 representing 50 farm-years (total of 186 strawberry fields) were used to determine potential crop losses and to study the influence of weather on disease occurrence and development. First, logistic regression was used to model the relationship between occurrence of BSD and weather variables. Second, linear and nonlinear regressions were used to model the number of black seed per berry (severity) and the percentage of diseased berries (incidence). Of the 186 fields monitored, 78 showed black seed symptoms, and the number of black seed per berry ranged from 1 to 10, whereas the percentage of diseased berries ranged from 3 to 32%. The most influential weather variable was total rainfall (in millimeters) in May, with a threshold of 103 mm of rain (absence of BSD < 103 mm < presence of BSD). Similarly, nonlinear models with the total rainfall in May accurately predicted both disease severity and incidence (r = 0.94 and 0.97, respectively). Considering that management actions such as fungicide application are not needed every year in every field, these models could be used to identify fields that are at risk of BSD.

National prevalence of coronary heart disease and its relationship with human development index: A systematic review.

PubMed

Zhu, Ke-Fu; Wang, Yu-Ming; Zhu, Jin-Zhou; Zhou, Qin-Yi; Wang, Ning-Fu

2016-03-01

Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index. Systematic review. The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value. Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively). With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors. © The European Society of Cardiology 2015.

Distribution and characterization of Podosphaera macularis virulent on hop cultivars possessing R6-based resistance to powdery mildew

USDA-ARS?s Scientific Manuscript database

In 2012, an epidemic of powdery mildew occurred in Washington and Idaho on previously resistant cultivars whose resistance was putatively based on the gene designated R6. In 2013, isolates capable of causing severe disease on cultivars with R6-based resistance were confirmed in Oregon and became wid...

Examining Success of Communication Strategies Used by Formal Caregivers Assisting Individuals with Alzheimer's Disease during an Activity of Daily Living

ERIC Educational Resources Information Center

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

2012-01-01

Purpose: To examine how formal (i.e., employed) caregivers' use verbal and nonverbal communication strategies while assisting individuals with moderate to severe Alzheimer's disease (AD) during the successful completion of an activity of daily living (ADL). Based on the literature, the authors hypothesized that caregivers' use of 1 proposition,…

Severity of scab and its effects on fruit weight in mechanically hedge-pruned and topped pecan trees

USDA-ARS?s Scientific Manuscript database

Scab is the most damaging disease of pecan in the southeastern USA. Pecan trees can attain 44 m in height, so managing disease in the upper canopy is a problem. Fungicide is ordinarily applied using ground-based air-blast sprayers. Although mechanical hedge-pruning and topping of pecan is done for s...

Object-based assessment of burn severity in diseased forests using high-spatial and high-spectral resolution MASTER airborne imagery

Treesearch

G. Chen; M.R. Metz; D.M. Rizzo; W.W. Dillon; R.K. Meentemeyer

2015-01-01

Forest ecosystems are subject to a variety of disturbances with increasing intensities and frequencies, which may permanently change the trajectories of forest recovery and disrupt the ecosystem services provided by trees. Fire and invasive species, especially exotic disease-causing pathogens and insects, are examples of disturbances that together could pose major...

Old and new challenges in Parkinson's disease therapeutics.

PubMed

Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

2017-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

PubMed

Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

2013-10-21

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

PubMed

Grassmann, Felix; Mengelkamp, Judith; Brandl, Caroline; Harsch, Sebastian; Zimmermann, Martina E; Linkohr, Birgit; Peters, Annette; Heid, Iris M; Palm, Christoph; Weber, Bernhard H F

2018-04-10

Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly. Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Models of cooperative dynamics from biomolecules to magnets

NASA Astrophysics Data System (ADS)

Mobley, David Lowell

This work details application of computer models to several biological systems (prion diseases and Alzheimer's disease) and a magnetic system. These share some common themes, which are discussed. Here, simple lattice-based models are applied to aggregation of misfolded protein in prion diseases like Mad Cow disease. These can explain key features of the diseases. The modeling is based on aggregation being essential in establishing the time-course of infectivity. Growth of initial aggregates is assumed to dominate the experimentally observed lag phase. Subsequent fission, regrowth, and fission set apart the exponential doubling phase in disease progression. We explore several possible modes of growth for 2-D aggregates and suggest the model providing the best explanation for the experimental data. We develop testable predictions from this model. Like prion disease, Alzheimer's disease (AD) is an amyloid disease characterized by large aggregates in the brain. However, evidence increasingly points away from these as the toxic agent and towards oligomers of the Abeta peptide. We explore one possible toxicity mechanism---insertion of Abeta into cell membranes and formation of harmful ion channels. We find that mutations in this peptide which cause familial Alzheimer's disease (FAD) also affect the insertion of this peptide into membranes in a fairly consistent way, suggesting that this toxicity mechanism may be relevant biologically. We find a particular inserted configuration which may be especially harmful and develop testable predictions to verify whether or not this is the case. Nucleation is an essential feature of our models for prion disease, in that it protects normal, healthy individuals from getting prion disease. Nucleation is important in many other areas, and we modify our lattice-based nucleation model to apply to a hysteretic magnetic system where nucleation has been suggested to be important. From a simple model, we find qualitative agreement with experiment, and make testable experimental predictions concerning time-dependence and temperature-dependence of the major hysteresis loop and reversal curves which have been experimentally verified. We argue why this model may be suitable for systems like these and explain implications for Ising-like models. We suggest implications for future modeling work. Finally, we present suggestions for future work in all three areas.

Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.

PubMed

Golden, Joseph W; Josleyn, Matthew; Mucker, Eric M; Hung, Chien-Fu; Loudon, Peter T; Wu, T C; Hooper, Jay W

2012-01-01

Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA.

Side-by-Side Comparison of Gene-Based Smallpox Vaccine with MVA in Nonhuman Primates

PubMed Central

Golden, Joseph W.; Josleyn, Matthew; Mucker, Eric M.; Hung, Chien-Fu; Loudon, Peter T.; Wu, T. C.; Hooper, Jay W.

2012-01-01

Orthopoxviruses remain a threat as biological weapons and zoonoses. The licensed live-virus vaccine is associated with serious health risks, making its general usage unacceptable. Attenuated vaccines are being developed as alternatives, the most advanced of which is modified-vaccinia virus Ankara (MVA). We previously developed a gene-based vaccine, termed 4pox, which targets four orthopoxvirus antigens, A33, B5, A27 and L1. This vaccine protects mice and non-human primates from lethal orthopoxvirus disease. Here, we investigated the capacity of the molecular adjuvants GM-CSF and Escherichia coli heat-labile enterotoxin (LT) to enhance the efficacy of the 4pox gene-based vaccine. Both adjuvants significantly increased protective antibody responses in mice. We directly compared the 4pox plus LT vaccine against MVA in a monkeypox virus (MPXV) nonhuman primate (NHP) challenge model. NHPs were vaccinated twice with MVA by intramuscular injection or the 4pox/LT vaccine delivered using a disposable gene gun device. As a positive control, one NHP was vaccinated with ACAM2000. NHPs vaccinated with each vaccine developed anti-orthopoxvirus antibody responses, including those against the 4pox antigens. After MPXV intravenous challenge, all control NHPs developed severe disease, while the ACAM2000 vaccinated animal was well protected. All NHPs vaccinated with MVA were protected from lethality, but three of five developed severe disease and all animals shed virus. All five NHPs vaccinated with 4pox/LT survived and only one developed severe disease. None of the 4pox/LT-vaccinated animals shed virus. Our findings show, for the first time, that a subunit orthopoxvirus vaccine delivered by the same schedule can provide a degree of protection at least as high as that of MVA. PMID:22860117

Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation.

PubMed

Blasi, Francesco; Neri, Luca; Centanni, Stefano; Falcone, Franco; Di Maria, Giuseppe

2017-02-01

Chronic obstructive pulmonary disease (COPD) patients experiencing several episodes of acute clinical derangement suffer from increased morbidity, mortality, and accelerated decline in lung function. Nevertheless, the relationship between co-morbidity profile and exacerbation rates in the frequent exacerbator phenotype is poorly characterized, and evidence-based management guidelines are lacking. We sought to evaluate the co-morbidity profile and treatment patterns of "frequent exacerbators" with severe or very severe airflow limitation. We conducted a cross-sectional, multicenter study in 50 Italian hospitals. Pulmonologists abstracted clinical information from medical charts of 743 COPD frequent exacerbators. We evaluated the exacerbation risk and center-related variations in diagnostic testing. One-third of patients (n = 210) underwent a bronchodilator response test, and 163 (22%) received a computerized tomography (CT) scan; 35 had a partial response to bronchodilators, while 119 had a diagnosis of emphysema; 584 (79%) lacked sufficient diagnostic testing for classification. Only 17% of patients did not have any coexistent disease. Cardiovascular conditions were the most frequent co-morbidities. A history of heart failure [odds ratio (OR): 1.89; 95% confidence interval (CI) 1.48-2.3] and affective disorders (OR: 1.66; 95% CI 1.24-2.1) was associated with the frequency of exacerbations. Center membership was strongly associated with exacerbation risk, independent of casemix (variance partition coefficient = 29.6%). Examining the regional variation in health outcomes and health care behavior may help identify the best practices, especially when evidence-based recommendations are lacking and uncertainties surround clinical decision-making.

Recommendations for incorporating biologicals into management of moderate to severe plaque psoriasis: individualized patient approaches.

PubMed

Langley, Richard G; Ho, Vincent; Lynde, Charles; Papp, Kim A; Poulin, Yves; Shear, Neil; Toole, Jack; Zip, Catherine

2006-01-01

Psoriasis is a T-cell mediated skin disease that affects approximately 2% of the population worldwide. Despite the prevalence of the disease and long-standing efforts to develop strategies to treat it, there is a need for safe and effective therapies to treat psoriasis, particularly the more severe forms. Biological agents such as alefacept, efalizumab, etanercept, and infliximab have been recognized as a class of treatment distinct from other forms of therapy in the treatment algorithm of psoriasis. Recent national and international consensus meetings have developed statements that position biological agents as an important addition to the treatment armamentarium for moderate to severe psoriasis, along with phototherapy and traditional systemic agents. There has been consensus that treatment should be individualized to each patient's needs and circumstances. Biological agents offer the hope of safe, effective, long-term management of moderate to severe psoriasis. As new agents receive approval from Health Canada, the available range of therapeutic options for treating this chronic disease will broaden. A Canadian Psoriasis Expert Panel recently convened in February 2005 to analyze, based on a series of clinical case scenarios, the indications, contraindications, and considerations for and against each of the four biological agents, derived from product labelling, where available, and from the efficacy and safety data from phase 3 and earlier clinical trials, as well as post-marketing reports. The Panel has formulated a set of recommendations for incorporating these biological agents into the current treatment paradigm of moderate to severe plaque psoriasis and has identified the preferred biological agents for each patient based on individual needs and circumstances.

School-Based Asthma Case Finding: The Arkansas Experience

ERIC Educational Resources Information Center

Vargas, Perla A.; Magee, James S.; Bushmiaer, Margo; Simpson, Pippa M.; Jones, Craig A.; Feild, Charles R.; Jones, Stacie M.

2006-01-01

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than…

Association of maternal chronic disease with risk of congenital heart disease in offspring

PubMed Central

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-01-01

Background: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. Methods: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan’s National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. Results: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66–3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60–3.12), hypertension (adjusted OR 1.87, 95% CI 1.69–2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45–3.80), anemia (adjusted OR 1.31, 95% CI 1.25–1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19–1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08–1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11–1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. Interpretation: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. PMID:27729382

Association of maternal chronic disease with risk of congenital heart disease in offspring.

PubMed

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-12-06

Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan's National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66-3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60-3.12), hypertension (adjusted OR 1.87, 95% CI 1.69-2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45-3.80), anemia (adjusted OR 1.31, 95% CI 1.25-1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19-1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08-1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11-1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. © 2016 Canadian Medical Association or its licensors.

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Relationship between indirect blood pressure and various stages of chronic kidney disease in cats.

PubMed

Hori, Yasutomo; Heishima, Yasuhiro; Yamashita, Yohei; Isayama, Noriko; Kanno, Nobuyuki; Nakamura, Kensuke; Iguchi, Masayuki; Ibaragi, Toshiki; Onodera, Hideyuki; Aramaki, Yoshitaka; Hirakawa, Atsushi; Yamano, Shigeki; Katagi, Michio; Kitade, Akihito; Sawada, Tamotsu

2018-03-24

Chronic kidney disease (CKD) is a common cause of secondary systemic hypertension in cats. We investigated the relationship between indirect blood pressure and the prevalence of systemic hypertension in various CKD stages in cats. Client-owned cats (24 control cats and 77 cats with CKD) were included. Biochemical examinations of plasma were conducted by a commercial laboratory. Diseased cats were divided into two groups based on the International Renal Interest Society (IRIS) guidelines (II and III-IV). Indirect blood pressure was measured using an oscillometric technique. Severe hypertension was diagnosed if systolic blood pressure (SBP) was ≥180 mmHg. Indirect blood pressures were significantly higher in IRIS stage III-IV than in the control cats. Of 77 cats with CKD, 25 (32.5%) had severe hypertension. The frequency of severe hypertension increased with an increase in IRIS stage; 0% in the controls, 27.6% in the IRIS stage II, and 47.4% in the IRIS stage III-IV, respectively. The indirect SBP was weakly correlated with urea nitrogen (r=0.27) and creatinine (r=0.23) concentrations in plasma. Binary logistic regression analysis showed that if plasma creatinine concentration is >3.7 mg/dl, cats with CKD had an increased risk for developing severe hypertension (P<0.001). Our results suggest that indirect blood pressure was correlated with the severity of CKD, and the prevalence of severe hypertension increased in cats with severe CKD. The risk of severe hypertension may be high in cats with severe CKD.

Laryngomalacia and Swallowing Function in Children

PubMed Central

Simons, Jeffrey P.; Greenberg, Laura L.; Mehta, Deepak K.; Fabio, Anthony; Maguire, Raymond C.; Mandell, David L.

2016-01-01

Objectives 1) To determine the prevalence of dysphagia in children with laryngomalacia; 2) To ascertain whether severity of laryngomalacia influences the presence of swallowing dysfunction; 3) To examine whether patients with medical comorbidities and laryngomalacia have a higher prevalence of swallowing dysfunction. Study Design Retrospective cohort study. Methods All patients seen in the Aerodigestive Center at our institution between January 2007 and December 2012 with the diagnosis of laryngomalacia were included. Swallowing function was assessed by symptoms, clinical swallowing evaluations (CSE) performed by speech pathologists, modified barium swallow studies (MBS), and fiberoptic endoscopic evaluations of swallowing (FEES). Results There were 324 patients with laryngomalacia identified (41.4% female; 58.6% male). Severity of laryngomalacia was categorized in 279 patients, with 62.7% mild, 28.7% moderate, and 8.6% severe. Gastroesophageal reflux disease (GERD) was diagnosed in 69.8% of patients. Other medical comorbidities included Down syndrome (3.1%), neurologic impairment (6.5%), and congenital heart disease (0.9%). Symptoms of dysphagia or feeding difficulty were present in 163/324 (50.3%) and failure to thrive was present in 31/324 patients (9.6%). At least one abnormal swallowing assessment was present in 97/120 (80.8%) patients presenting with subjective dysphagia and 43/65 (66.2%) patients without subjective dysphagia. A total of 140/185 (75.7%) patients had at least one abnormal baseline swallowing assessment. There was no significant relationship between severity of laryngomalacia and presence of abnormal swallowing function based on symptoms, CSE, MBS, or FEES. However, patients with greater severity were more likely to have failure to thrive. There was not a significant association between the presence of swallowing dysfunction or disease severity and medical comorbidities such as Down syndrome, neurologic impairment, or congenital heart disease. However, GERD was more likely to be present in patients with moderate and severe laryngomalacia than in patients with mild disease. Conclusion Swallowing dysfunction is common in children with laryngomalacia regardless of disease severity or other medical comorbidities. Swallowing studies are frequently abnormal in laryngomalacia patients presenting both with and without subjective symptoms of dysphagia. Dysphagia assessment should be considered as part of the evaluation of infants with laryngomalacia. Level of evidence 4 PMID:26152504

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

PubMed

Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

2014-10-15

To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

PubMed Central

Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

2014-01-01

Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients.

PubMed

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Lozano, M Luz; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-06-01

Previous clinical trials based on the genetic correction of purified CD34(+) cells with gamma-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34(+) cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34(+) cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34(-) mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs).

Lentiviral-mediated Genetic Correction of Hematopoietic and Mesenchymal Progenitor Cells From Fanconi Anemia Patients

PubMed Central

Jacome, Ariana; Navarro, Susana; Río, Paula; Yañez, Rosa M; González-Murillo, Africa; Luz Lozano, M; Lamana, Maria Luisa; Sevilla, Julian; Olive, Teresa; Diaz-Heredia, Cristina; Badell, Isabel; Estella, Jesus; Madero, Luis; Guenechea, Guillermo; Casado, José; Segovia, Jose C; Bueren, Juan A

2009-01-01

Previous clinical trials based on the genetic correction of purified CD34+ cells with γ-retroviral vectors have demonstrated clinical efficacy in different monogenic diseases, including X-linked severe combined immunodeficiency, adenosine deaminase deficient severe combined immunodeficiency and chronic granulomatous disease. Similar protocols, however, failed to engraft Fanconi anemia (FA) patients with genetically corrected cells. In this study, we first aimed to correlate the hematological status of 27 FA patients with CD34+ cell values determined in their bone marrow (BM). Strikingly, no correlation between these parameters was observed, although good correlations were obtained when numbers of colony-forming cells (CFCs) were considered. Based on these results, and because purified FA CD34+ cells might have suboptimal repopulating properties, we investigated the possibility of genetically correcting unselected BM samples from FA patients. Our data show that the lentiviral transduction of unselected FA BM cells mediates an efficient phenotypic correction of hematopoietic progenitor cells and also of CD34− mesenchymal stromal cells (MSCs), with a reported role in hematopoietic engraftment. Our results suggest that gene therapy protocols appropriate for the treatment of different monogenic diseases may not be adequate for stem cell diseases like FA. We propose a new approach for the gene therapy of FA based on the rapid transduction of unselected hematopoietic grafts with lentiviral vectors (LVs). PMID:19277017

Evaluation of a novel Serious Game based assessment tool for patients with Alzheimer's disease.

PubMed

Vallejo, Vanessa; Wyss, Patric; Rampa, Luca; Mitache, Andrei V; Müri, René M; Mosimann, Urs P; Nef, Tobias

2017-01-01

Despite growing interest in developing ecological assessment of difficulties in patients with Alzheimer's disease new methods assessing the cognitive difficulties related to functional activities are missing. To complete current evaluation, the use of Serious Games can be a promising approach as it offers the possibility to recreate a virtual environment with daily living activities and a precise and complete cognitive evaluation. The aim of the present study was to evaluate the usability and the screening potential of a new ecological tool for assessment of cognitive functions in patients with Alzheimer's disease. Eighteen patients with Alzheimer's disease and twenty healthy controls participated to the study. They were asked to complete six daily living virtual tasks assessing several cognitive functions: three navigation tasks, one shopping task, one cooking task and one table preparation task following a one-day scenario. Usability of the game was evaluated through a questionnaire and through the analysis of the computer interactions for the two groups. Furthermore, the performances in terms of time to achieve the task and percentage of completion on the several tasks were recorded. Results indicate that both groups subjectively found the game user friendly and they were objectively able to play the game without computer interactions difficulties. Comparison of the performances between the two groups indicated a significant difference in terms of percentage of achievement of the several tasks and in terms of time they needed to achieve the several tasks. This study suggests that this new Serious Game based assessment tool is a user-friendly and ecological method to evaluate the cognitive abilities related to the difficulties patients can encounter in daily living activities and can be used as a screening tool as it allowed to distinguish Alzheimer's patient's performance from healthy controls.

A current view of Alzheimer's disease.

PubMed

Hooli, Basavaraj V; Tanzi, Rudolph E

2009-07-08

Several genes that influence susceptibility to Alzheimer's disease (AD) have been known for over two decades. Recent advances have elucidated novel candidate genes and the pathogenetic mechanisms underlying neurodegeneration in AD. Here, we summarize what we have learned from studies of the known AD genes with regard to the causes of AD and emerging therapies. We also review key recent discoveries that have enhanced our understanding of the etiology and pathogenesis of this devastating disease, based on new investigations into the genes and molecular mechanisms underlying AD.

MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.

PubMed

Barbado, Julia; Martin, Debora; Vega, Luisa; Almansa, Raquel; Gonçalves, Lisbeth; Nocito, Mercedes; Jimeno, Antonio; Ortiz de Lejarazu, Raúl; Bermejo-Martin, Jesus F

2012-11-01

Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Oral, Maxillofacial and Dental Diseases in Captive Cheetahs (Acinonyx jubatus).

PubMed

Steenkamp, G; Boy, S C; van Staden, P J; Bester, M N

2018-01-01

Descriptions of several oral, maxillofacial and dental conditions/diseases exist for a variety of captive large felids, but little is reported on the pathology of free roaming large felids. Apart from focal palatine erosions (FPEs) as initially described by Fitch and Fagan (1982) and some reference to absent incisor teeth, few data exist on diseases affecting the oral, maxillofacial and dental structures of cheetahs (Acinonyx jubatus), regardless of their captivity status. This study reports 18 different conditions affecting the teeth, bone and oral cavity soft tissue of cheetahs, based on initial assessment of 256 animals over 11 years (2002-2012) in South Africa and Namibia. This report excludes oral tumours or FPEs, but includes several acquired and developmental conditions never described before. Copyright © 2017 Elsevier Ltd. All rights reserved.

Real-time forecasts of dengue epidemics

NASA Astrophysics Data System (ADS)

Yamana, T. K.; Shaman, J. L.

2015-12-01

Dengue is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas with endemic dengue, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission is a significant public health challenge. Here we present a model of dengue transmission and a framework for optimizing model simulations with real-time observational data of dengue cases and environmental variables in order to generate ensemble-based forecasts of the timing and severity of disease outbreaks. The model-inference system is validated using synthetic data and dengue outbreak records. Retrospective forecasts are generated for a number of locations and the accuracy of these forecasts is quantified.

Chronic obstructive pulmonary disease: knowing what we mean, meaning what we say.

PubMed

Joshi, J M

2008-01-01

Chronic obstructive pulmonary disease (COPD) is defined in several different ways using different criteria based on symptoms, physiological impairment and pathological abnormalities. While some use COPD to mean smoking related chronic airway disease, others include all disorders causing chronic airway obstruction. When COPD is used as a broad descriptive term, specific disorders that cause chronic airway obstruction remain under-diagnosed and the prevalence estimates vary considerably. The lack of agreement over the precise terminology and classification of COPD has resulted in widespread confusion. Terminology includes definition, diagnostic criteria, and a system for staging severity. Recently, COPD is defined more clearly and diagnosed using precise criteria that include tobacco smoking greater than 10 pack years, symptoms and airway obstruction on spirometry. A multi-dimensional severity grading system, the BODE (body mass index, obstruction, dyspnoea, and exercise tolerance) index has been designed to assess the respiratory and systemic expressions of COPD. This review proposes that the broad group of chronic disorders of the airways (with or without airway obstruction) be called chronic airway disease (CAD). The term COPD should be used exclusively for tobacco smoking related chronic airway disease. Chronic airway obstruction or obstructive lung disease may be used to define those conditions with airways obstruction caused by factors other than tobacco smoking. The aetiology may be appended to the label, for example, chronic airway obstruction/obstructive lung disease associated with bronchiectasis, chronic airway obstruction/obstructive lung disease associated with obliterative bronchiolitis or chronic airway obstruction/obstructive lung disease due to biomass fuel/occupational exposure.

Extracorporeal shock wave therapy for ischemic cardiovascular disorders.

PubMed

Ito, Kenta; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2011-10-01

Ischemic heart disease is the leading cause of death and a major cause of hospital admissions, with the number of affected patients increasing worldwide. The current management of ischemic heart disease has three major therapeutic options: medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, the prognosis for patients with severe ischemic heart disease without indications for PCI or CABG still remains poor due to the lack of effective treatments. It is therefore crucial to develop alternative therapeutic strategies for severe ischemic heart disease. Extracorporeal shock wave (SW) therapy was introduced clinically more than 20 years ago to fragment kidney stones, which has markedly improved the treatment of urolithiasis. We found that a low-energy SW (about 10% of the energy density used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we initiated in vivo studies and have demonstrated that extracorporeal cardiac SW therapy with a low-energy SW up-regulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia, without any adverse effects in vivo. On the basis of promising results in animal studies, we performed a series of clinical studies in patients with severe coronary artery disease without indication for PCI or CABG, including, firstly, an open trial followed by a placebo-controlled, double-blind study. In both studies, our extracorporeal cardiac SW therapy improved symptoms, exercise capacity, and myocardial perfusion in patients with severe coronary artery disease. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction (MI) in pigs and in enhancing angiogenesis in hind-limb ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute MI and in those with peripheral artery disease. Thus, our extracorporeal cardiac SW therapy appears to be an effective, safe, and non-invasive angiogenic approach in cardiovascular medicine and its indication could be extended to a variety of ischemic diseases in the near future. In this article, we briefly summarize our work in animals and humans, and discuss the advantages and perspectives of our extracorporeal SW therapy.

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.

ICD-9-CM and ICD-10-CM mapping of the AAST Emergency General Surgery disease severity grading systems: Conceptual approach, limitations, and recommendations for the future.

PubMed

Utter, Garth H; Miller, Preston R; Mowery, Nathan T; Tominaga, Gail T; Gunter, Oliver; Osler, Turner M; Ciesla, David J; Agarwal, Suresh K; Inaba, Kenji; Aboutanos, Michel B; Brown, Carlos V R; Ross, Steven E; Crandall, Marie L; Shafi, Shahid

2015-05-01

The American Association for the Surgery of Trauma (AAST) recently established a grading system for uniform reporting of anatomic severity of several emergency general surgery (EGS) diseases. There are five grades of severity for each disease, ranging from I (lowest severity) to V (highest severity). However, the grading process requires manual chart review. We sought to evaluate whether International Classification of Diseases, 9th and 10th Revisions, Clinical Modification (ICD-9-CM, ICD-10-CM) codes might allow estimation of AAST grades for EGS diseases. The Patient Assessment and Outcomes Committee of the AAST reviewed all available ICD-9-CM and ICD-10-CM diagnosis codes relevant to 16 EGS diseases with available AAST grades. We then matched grades for each EGS disease with one or more ICD codes. We used the Official Coding Guidelines for ICD-9-CM and ICD-10-CM and the American Hospital Association's "Coding Clinic for ICD-9-CM" for coding guidance. The ICD codes did not allow for matching all five AAST grades of severity for each of the 16 diseases. With ICD-9-CM, six diseases mapped into four categories of severity (instead of five), another six diseases into three categories of severity, and four diseases into only two categories of severity. With ICD-10-CM, five diseases mapped into four categories of severity, seven diseases into three categories, and four diseases into two categories. Two diseases mapped into discontinuous categories of grades (two in ICD-9-CM and one in ICD-10-CM). Although resolution is limited, ICD-9-CM and ICD-10-CM diagnosis codes might have some utility in roughly approximating the severity of the AAST grades in the absence of more precise information. These ICD mappings should be validated and refined before widespread use to characterize EGS disease severity. In the long-term, it may be desirable to develop alternatives to ICD-9-CM and ICD-10-CM codes for routine collection of disease severity characteristics.

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.

Image-Based Quantification of Plant Immunity and Disease.

PubMed

Laflamme, Bradley; Middleton, Maggie; Lo, Timothy; Desveaux, Darrell; Guttman, David S

2016-12-01

Measuring the extent and severity of disease is a critical component of plant pathology research and crop breeding. Unfortunately, existing visual scoring systems are qualitative, subjective, and the results are difficult to transfer between research groups, while existing quantitative methods can be quite laborious. Here, we present plant immunity and disease image-based quantification (PIDIQ), a quantitative, semi-automated system to rapidly and objectively measure disease symptoms in a biologically relevant context. PIDIQ applies an ImageJ-based macro to plant photos in order to distinguish healthy tissue from tissue that has yellowed due to disease. It can process a directory of images in an automated manner and report the relative ratios of healthy to diseased leaf area, thereby providing a quantitative measure of plant health that can be statistically compared with appropriate controls. We used the Arabidopsis thaliana-Pseudomonas syringae model system to show that PIDIQ is able to identify both enhanced plant health associated with effector-triggered immunity as well as elevated disease symptoms associated with effector-triggered susceptibility. Finally, we show that the quantitative results provided by PIDIQ correspond to those obtained via traditional in planta pathogen growth assays. PIDIQ provides a simple and effective means to nondestructively quantify disease from whole plants and we believe it will be equally effective for monitoring disease on excised leaves and stems.

Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD)

PubMed Central

2012-01-01

Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty member_giacomini.htm. For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx. The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact. Objective The objective of this health technology assessment was to determine the effectiveness, cost-effectiveness, and safety of long-term oxygen therapy (LTOT) for chronic obstructive pulmonary disease (COPD). Clinical Need: Condition and Target Population Oxygen therapy is used in patients with COPD with hypoxemia, or very low blood oxygen levels, because they may have difficulty obtaining sufficient oxygen from inspired air. Technology Long-term oxygen therapy is extended use of oxygen. Oxygen therapy is delivered as a gas from an oxygen source. Different oxygen sources are: 1) oxygen concentrators, electrical units delivering oxygen converted from room air; 2) liquid oxygen systems, which deliver gaseous oxygen stored as liquid in a tank; and 3) oxygen cylinders, which contain compressed gaseous oxygen. All are available in portable versions. Oxygen is breathed in through a nasal cannula or through a mask covering the mouth and nose. The treating clinician determines the flow rate, duration of use, method of administration, and oxygen source according to individual patient needs. Two landmark randomized controlled trials (RCTs) of patients with COPD established the role of LTOT in COPD. Questions regarding the use of LTOT, however, still remain. Research Question What is the effectiveness, cost-effectiveness, and safety of LTOT compared with no LTOT in patients with COPD, who are stratified by severity of hypoxemia? Research Methods Literature Search Search Strategy A literature search was performed on September 8, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, CINAHL, the Cochrane Library, and INAHTA for studies published from January 1, 2007 to September 8, 2010. A single clinical epidemiologist reviewed the abstracts, obtained full-text articles for studies meeting the eligibility criteria, and examined reference lists for additional relevant studies not identified through the literature search. A second clinical epidemiologist and then a group of epidemiologists reviewed articles with an unknown eligibility until consensus was established. Inclusion Criteria patients with mild, moderate, or severe hypoxemia; English-language articles published between January 1, 2007 and September 8, 2010; journal articles reporting on effectiveness, cost-effectiveness, or safety for the comparison of interest; clearly described study design and methods; health technology assessments, systematic reviews, RCTs, or prospective cohort observational studies; any type of observational study for the evaluation of safety. Exclusion Criteria no hypoxemia non-English papers animal or in vitro studies case reports, case series, or case-case studies studies comparing different oxygen therapy regimens studies on nocturnal oxygen therapy studies on short-burst, palliative, or ambulatory oxygen (supplemental oxygen during exercise or activities of daily living) Outcomes of Interest mortality/survival hospitalizations readmissions forced expiratory volume in 1 second (FEV1) forced vital capacity (FVC) FEV1/FVC pulmonary hypertension arterial partial pressure of oxygen (PaO2) arterial partial pressure of carbon dioxide (PaCO2) end-exercise dyspnea score endurance time health-related quality of life Note: Outcomes of interest were formulated according to existing studies, with arterial pressure of oxygen and carbon dioxide as surrogate outcomes. Summary of Findings Conclusions Based on low quality of evidence, LTOT (~ 15 hours/day) decreases all-cause mortality in patients with COPD who have severe hypoxemia (PaO2 ~ 50 mm Hg) and heart failure. The effect for all-cause mortality had borderline statistical significance when the control group was no LTOT: one study. Based on low quality of evidence, there is no beneficial effect of LTOT on all-cause mortality at 3 and 7 years in patients with COPD who have mild-to-moderate hypoxemia (PaO2 ~ 59-65 mm Hg)1 Based on very low quality of evidence, there is some suggestion that LTOT may have a beneficial effect over time on FEV1 and PaCO2 in patients with COPD who have severe hypoxemia and heart failure: improved methods are needed. Based on very low quality of evidence, there is no beneficial effect of LTOT on lung function or exercise factors in patients with COPD who have mild-to-moderate hypoxemia, whether survivors or nonsurvivors are assessed. Based on low to very low quality of evidence, LTOT does not prevent readmissions in patients with COPD who have severe hypoxemia. Limited data suggest LTOT increases the risk of hospitalizations. Limited work has been performed evaluating the safety of LTOT by severity of hypoxemia. Based on low to very low quality of evidence, LTOT may have a beneficial effect over time on health-related quality of life in patients with COPD who have severe hypoxemia. Limited work using disease-specific instruments has been performed. Ethical constraints of not providing LTOT to eligible patients with COPD prohibit future studies from examining LTOT outcomes in an ideal way. PMID:23074435

Metabolomics-based promising candidate biomarkers and pathways in Alzheimer's disease.

PubMed

Kang, Jian; Lu, Jingli; Zhang, Xiaojian

2015-05-01

Pathologically, loss of synapses and neurons, extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) are observed in the brains of patients with Alzheimer's disease (AD). These features are associated with changes Aβ (amyloid β) 40, Aβ42, total tau and phosphorylated tau (p-tau), which are as definitely biomarkers for severe AD state. However, biomarkers for effectively diagnosing AD in the pre-clinical state for directing therapeutic strategies are lacking. Metabolic profiling as a powerful tool to identify new biomarkers is receiving increasing attention in AD. This review will focus on metabolomics-based detection of promising candidate biomarkers and pathways in AD to facilitate the discovery of new medicines and disease pathways.

Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

PubMed

Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

2018-01-01

Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine

PubMed Central

Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo

2018-01-01

Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis. PMID:29765977

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

Cellular metabolism and disease: what do metabolic outliers teach us?

PubMed Central

DeBerardinis, Ralph J.; Thompson, Craig B.

2012-01-01

An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

Remote sensing of St. Augustine Decline (SAD) disease. [spectral reflectance of healthy and diseased grass

NASA Technical Reports Server (NTRS)

Odle, W. C.

1976-01-01

Laboratory and field spectral reflectance measurements of healthy and infected St. Augustine grass were made using several different instruments. Spectral differences between healthy and infected grass occured in the visible and near infrared regions. Multiband and color infrared photographs were taken of healthy and diseased turf from ground-based platforms and low altitude aircraft. Qualitative (density slicing) and quantitative (transmission densitometry) analyses revealed distinct tonal differences between healthy and St. Augustine disease (SAD) infected grass. Similar experiments are described for determining if healthy and diseased grass can be distinguished from waterstressed grass and grass deficient in either nitrogen or iron.

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.

Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

PubMed Central

Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

2017-01-01

Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

[Relevance of medical rehabilitation in disease management programmes].

PubMed

Lüngen, M; Lauterbach, K W

2003-10-01

Disease management programmes will increasingly be introduced in Germany due to the new risk adjustment scheme. The first disease management programmes started in 2003 for breast cancer and diabetes mellitus type II. German rehabilitation will have to face several challenges. Disease management programmes are strongly based on the notion of Evidence so that proof of the efficacy of a care giving task should be present. Verification of the evidence of the specifically German rehabilitation treatments must therefore be given. However, integration of rehabilitation in disease management programmes could lead to changes in the alignment of German rehabilitation. The essence of German rehabilitation, notably its holistic approach, could get lost with integration in disease management programmes.

Association between nutritional status and disease severity using the amyotrophic lateral sclerosis (ALS) functional rating scale in ALS patients.

PubMed

Park, Yongsoon; Park, Jinhee; Kim, Yeonsun; Baek, Heejoon; Kim, Seung Hyun

2015-01-01

The nutritional status of patients with amyotrophic lateral sclerosis (ALS) has been shown to be associated with mortality. However, there have not been, to our knowledge, any studies on the association between nutritional status and disease severity. The present study investigated the hypothesis that nutritional status was negatively associated with disease severity using the ALS functional rating scale (ALSFRS-R). One hundred ninety-three Korean ALS patients were divided into tertiles based on their ALSFRS-R score. Dietary intake was measured using 24 h recall and nutritional status was determined by body mass index (BMI) and geriatric nutritional risk index (GNRI). BMI and GNRI were significantly lower in patients in the lowest tertile of ALSFRS-R. BMI and GNRI also correlated with ALSFRS-R score, bulbar score, albumin levels, total lymphocyte count, and total daily energy expenditure. Intakes of energy and most nutrients were significantly lower in patients in the lowest tertiles of ALSFRS-R, but significances disappeared after adjusting for energy intake. Intakes of vegetables, grains, seasonings, and oils were also significantly lower in patients in the lowest tertile of ALSFRS-R. In addition, patients in the lowest tertile of ALSFRS-R were significantly younger at disease onset, had a longer duration of ALS, less regular exercise, and less sun exposure. Nutritional status, as assessed by BMI and GNRI, was negatively associated with disease severity using ALSFRS-R. The present study suggested that intake of nutrients decreases with disease progression in ALS patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic-based prediction of disease traits: prediction is very difficult, especially about the future†

PubMed Central

Schrodi, Steven J.; Mukherjee, Shubhabrata; Shan, Ying; Tromp, Gerard; Sninsky, John J.; Callear, Amy P.; Carter, Tonia C.; Ye, Zhan; Haines, Jonathan L.; Brilliant, Murray H.; Crane, Paul K.; Smelser, Diane T.; Elston, Robert C.; Weeks, Daniel E.

2014-01-01

Translation of results from genetic findings to inform medical practice is a highly anticipated goal of human genetics. The aim of this paper is to review and discuss the role of genetics in medically-relevant prediction. Germline genetics presages disease onset and therefore can contribute prognostic signals that augment laboratory tests and clinical features. As such, the impact of genetic-based predictive models on clinical decisions and therapy choice could be profound. However, given that (i) medical traits result from a complex interplay between genetic and environmental factors, (ii) the underlying genetic architectures for susceptibility to common diseases are not well-understood, and (iii) replicable susceptibility alleles, in combination, account for only a moderate amount of disease heritability, there are substantial challenges to constructing and implementing genetic risk prediction models with high utility. In spite of these challenges, concerted progress has continued in this area with an ongoing accumulation of studies that identify disease predisposing genotypes. Several statistical approaches with the aim of predicting disease have been published. Here we summarize the current state of disease susceptibility mapping and pharmacogenetics efforts for risk prediction, describe methods used to construct and evaluate genetic-based predictive models, and discuss applications. PMID:24917882

A systems biology-led insight into the role of the proteome in neurodegenerative diseases.

PubMed

Fasano, Mauro; Monti, Chiara; Alberio, Tiziana

2016-09-01

Multifactorial disorders are the result of nonlinear interactions of several factors; therefore, a reductionist approach does not appear to be appropriate. Proteomics is a global approach that can be efficiently used to investigate pathogenetic mechanisms of neurodegenerative diseases. Here, we report a general introduction about the systems biology approach and mechanistic insights recently obtained by over-representation analysis of proteomics data of cellular and animal models of Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders, as well as of affected human tissues. Expert commentary: As an inductive method, proteomics is based on unbiased observations that further require validation of generated hypotheses. Pathway databases and over-representation analysis tools allow researchers to assign an expectation value to pathogenetic mechanisms linked to neurodegenerative diseases. The systems biology approach based on omics data may be the key to unravel the complex mechanisms underlying neurodegeneration.

Discrimination of inflammatory bowel disease using Raman spectroscopy and linear discriminant analysis methods

NASA Astrophysics Data System (ADS)

Ding, Hao; Cao, Ming; DuPont, Andrew W.; Scott, Larry D.; Guha, Sushovan; Singhal, Shashideep; Younes, Mamoun; Pence, Isaac; Herline, Alan; Schwartz, David; Xu, Hua; Mahadevan-Jansen, Anita; Bi, Xiaohong

2016-03-01

Inflammatory bowel disease (IBD) is an idiopathic disease that is typically characterized by chronic inflammation of the gastrointestinal tract. Recently much effort has been devoted to the development of novel diagnostic tools that can assist physicians for fast, accurate, and automated diagnosis of the disease. Previous research based on Raman spectroscopy has shown promising results in differentiating IBD patients from normal screening cases. In the current study, we examined IBD patients in vivo through a colonoscope-coupled Raman system. Optical diagnosis for IBD discrimination was conducted based on full-range spectra using multivariate statistical methods. Further, we incorporated several feature selection methods in machine learning into the classification model. The diagnostic performance for disease differentiation was significantly improved after feature selection. Our results showed that improved IBD diagnosis can be achieved using Raman spectroscopy in combination with multivariate analysis and feature selection.

The Epidemiology of Sleep Disordered Breathing and Hypertension in Various Populations.

PubMed

Sawatari, Hiroyuki; Chishaki, Akiko; Ando, Shin-ich

2016-01-01

Hypertension is prevalent in patients with sleep disordered breathing (SDB). Since hypertension significantly relates to cardiovascular diseases, the treatment and prevention of SDB could be targets for the prevention of cardiovascular diseases. In this article, we summarize about epidemiology of SDB and hypertension in various populations. General population based studies on the prevalence of SDB reported that 24 to 47% male and 9 to 30% female had SDB. Furthermore, the prevalence of hypertension in individuals with SDB was high, ranging from 36 to 57%. American and Korean based studies reported that the severity of SDB related to increase of blood pressure and hypertension. In the elderly, however, the severity of SDB did not relate to increase in blood pressure and hypertension, but to dipping pattern of blood pressure. With respect to children, the severity of SDB also related to increase in blood pressure, but the trend was inconstant in children with habitual snoring. In addition to the sexual differences, the severity of SDB related to hypertension in males. On the other hand, there was no relationship between the severity of SDB and hypertension in females. SDB was prevalent in the general population, regardless of race, and affected blood pressure. We should pay attention to the subjects' individual character when we interrupt the outcome.

A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

NASA Astrophysics Data System (ADS)

Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

2011-03-01

This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

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.

The relationship between different diet quality indices and severity of airflow obstruction among COPD patients

PubMed Central

Yazdanpanah, Leila; Paknahad, Zamzam; Moosavi, Ali Javad; Maracy, Mohammad Reza; Zaker, Mohammad Masoud

2016-01-01

Background: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. Smoking is the number one cause of COPD; however, genetic, environmental and dietary factors contribute to the etiology of this disease. In this study, we assessed the association between three diet quality indices -the Healthy Eating Index-2005 (HEI-2005), the Healthy Eating Index-2010 (HEI-2010), and Mediterranean Diet Score (MED)- and the severity of disease in COPD patients. Methods: This cross-sectional study was performed at Rasul-e-Akram Hospital in Tehran on 121 COPD patients with the mean age of (SD) of 66.1(10.9) years. A pulmonary specialist diagnosed all participants based on a spirometry test. They were categorized into four groups (1, 2, 3, 4 stages of disease). Three diet quality indices, spirometry test and determination of disease severity were performed for all the participants. ANCOVA and Kruskal-Wallis test were used to assess the relationship between dietary quality indices and severity of the disease. The relationship between HEI-2010, HEI-2005, MED score, their components and lung function was assessed using a multiple linear regression analysis. All analyses were done using SPSS 18. Results: Reduction of the Healthy Eating Index-2010 and MED score were observed along with the increase in disease severity, but they were not significant. The relationship between the three diet quality indices and lung function showed a significant association between MED score and Forced expiratory volume in one second (FEV1), The Forced Vital Capacity (FVC) (β=2.9, 95% CI (1.1, 4.8), p=0.002), (β=2.8, 95% CI (0.9, 4.8), p=0.007), respectively. Conclusion: Mediterranean dietary pattern and obtaining a better score on HEI-2010 diet were associated with a better lung function test. PMID:27493924

Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

PubMed

Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

2017-05-01

Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

The ability of cancer-specific and generic preference-based instruments to discriminate across clinical and self-reported measures of cancer severities

PubMed Central

2011-01-01

Objective To evaluate the validity of cancer-specific and generic preference-based instruments to discriminate across different measures of cancer severities. Methods Patients with breast (n = 66), colorectal (n = 57), and lung (n = 61) cancer completed the EORTC QLQ-C30 and the FACT-G, as well as three generic instruments: the EQ-5D, the SF-6D, and the HUI2/3. Disease severity was quantified using cancer stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score, and self-reported health status. Comparative analyses confirmed the multi-dimensional conceptualization of the instruments in terms of construct and convergent validity. Results In general, the instruments were able to discriminate across severity measures. The instruments demonstrated moderate to strong correlation with each other (r = 0.37-0.73). Not all of the measures could discriminate between different groups of disease severity: the EQ-5D and SF-6D were less discriminative than the HUI2/3 and the cancer-specific instruments. Conclusion The cancer-specific and generic preference-based instruments demonstrated to be valid in discriminating across levels of ECOG-PS scores and self-reported health states. However, the usefulness of the generic instruments may be limited if they are not able to detect small changes in health status within cancer patients. This raises concerns regarding the appropriateness of these instruments when comparing different cancer treatments within an economic evaluation framework. PMID:22123196

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis.

PubMed

Rich, Nicole E; Oji, Stefany; Mufti, Arjmand R; Browning, Jeffrey D; Parikh, Neehar D; Odewole, Mobolaji; Mayo, Helen; Singal, Amit G

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75-100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta-analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population-based or high-risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. In a systematic review and meta-analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Histomonosis in poultry: previous and current strategies for prevention and therapy.

PubMed

Liebhart, D; Ganas, P; Sulejmanovic, T; Hess, M

2017-02-01

Histomonosis is a parasitic disease of poultry with worldwide prevalence. The disease can cause morbidity and mortality in chicken and turkey flocks entailing severe economic losses. In the first half of the last century, there was a high demand to control histomonosis as the turkey industry was severely affected by the disease. Consequently, numerous chemical compounds were tested for their efficacy against Histomonas meleagridis with varying outcomes, that are summarized and specified in this review. At the same time, preliminary attempts to protect birds with cultured histomonads indicated the possibility of vaccination. Several years ago antihistomonal drugs were banned in countries with tight regulations on pharmaceuticals in order to comply with the demand of consumer protection. As a consequence, outbreaks of histomonosis in poultry flocks increased and the disease became endemic again. New approaches to prevent and treat histomonosis are, therefore, needed and recently performed studies focused on various areas to combat the disease, from alternative chemotherapeutic substances to plant-derived compounds until vaccination, altogether reviewed here. Considering existing regulations and the overall outcome of experimental studies, it can be concluded that vaccination is very promising, despite the fact that various challenges need to be addressed until the first ever developed vaccine based upon live flagellates in human or bird medicine can be marketed.

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.

Signal and image processing for early detection of coronary artery diseases: A review

NASA Astrophysics Data System (ADS)

Mobssite, Youness; Samir, B. Belhaouari; Mohamad Hani, Ahmed Fadzil B.

2012-09-01

Today biomedical signals and image based detection are a basic step to diagnose heart diseases, in particular, coronary artery diseases. The goal of this work is to provide non-invasive early detection of Coronary Artery Diseases relying on analyzing images and ECG signals as a combined approach to extract features, further classify and quantify the severity of DCAD by using B-splines method. In an aim of creating a prototype of screening biomedical imaging for coronary arteries to help cardiologists to decide the kind of treatment needed to reduce or control the risk of heart attack.

Severe acute malnutrition and infection

PubMed Central

Jones, Kelsey D J; Berkley, James A

2014-01-01

Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

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.

Inflammatory bowel disease in India - Past, present and future.

PubMed

Ray, Gautam

2016-09-28

There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of "hygiene hypothesis" is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn's disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease definition and treatment.

The study of the oipA and dupA genes in Helicobacter pylori strains and their relationship with different gastroduodenal diseases.

PubMed

Souod, Negar; Sarshar, Meysam; Dabiri, Hossein; Momtaz, Hassan; Kargar, Mohammad; Mohammadzadeh, Alireza; Abdi, Saeed

2015-01-01

The purpose of this investigation was to determine the oipA and dupA genes of Helicobacter pylori isolates from west of Iran; Chaharmahalo Bakhtiyari region and find their relationship with the severity of the gastroduodenal diseases. Helicobacter pylori is an organism responsible for many gastroduodenal diseases. Many studies suggest that genetic diversity in H . pylori virulence factors such as oipA and dupA genes is high among isolates of different geographic regions and may cause more severe diseases. In this cross-sectional study, gastric biopsy specimens were taken from 150 patients suffering from gastroduodenal diseases. The presence of ureC, dupA and oipA genes was tested by polymerase chain reaction (PCR). Overall, 123 (82%) H. pylori strains were isolated from 150 specimens. dupA gene was detected in 41 (33.33%) H.pylori-positive specimens. There was a reverse correlation between this gene and gastric cancer. The oipA gene was found in 88 (71.54%) samples and statistically there was no association between this gene and gastric disorders. As statistical analyses revealed, the presence of the dupA was more common in isolates with the oipA negative. Based on our findings, the presence of dupA gene can be considered as a marker for the onset of severe diseases. However, the oipA gene cannot be regarded for prediction of gastroenterology diseases. Meanwhile, extended molecular epidemiology researches in other populations are recommended.

Optimal health insurance: the case of observable, severe illness.

PubMed

Chernew, M E; Encinosa, W E; Hirth, R A

2000-09-01

We explore optimal cost-sharing provisions for insurance contracts when individuals have observable, severe diseases with a discrete number of medically appropriate treatment options. Variation in preferences for alternative treatments is unobserved by the insurer and non-contractible. Interest in such situations is increasingly common, exemplified by disease carve-out programs and shared decision-making (SDM) tools. We demonstrate that optimal insurance charges a copay to patients choosing the high-cost treatment and provides consumers of the low-cost treatment a cash payment. A simulation of the effect of such a policy, based on prostate cancer, indicates a substantial reduction in moral hazard.

Chikungunya Virus: Pathophysiology, Mechanism, and Modeling

PubMed Central

Ganesan, Vaishnavi K.; Reid, St Patrick

2017-01-01

Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models. PMID:29194359

Mindfulness-based group therapy for systemic lupus erythematosus: A first exploration of a promising mind-body intervention.

PubMed

Horesh, Danny; Glick, Ittai; Taub, Renen; Agmon-Levin, Nancy; Shoenfeld, Yehuda

2017-02-01

Psychological effects related to systemic lupus erythematosus (SLE) are tremendous. While a variety of psychological treatments have been applied to assist SLE patients, the effects of mindfulness practice were never documented in SLE. Mindfulness-based psychotherapy includes several techniques, including body-scan, breathing exercises, and full awareness during daily activities. In this case report, we present a first attempt at conducting mindfulness-based group therapy among SLE patients. Six female SLE patients participated in an 8-week program. Improvement was observed in several areas: patients' increased ability to differentiate between themselves and the disease; increased ability to accept, rather than to actively fight the fact that one must live with the disease; and decreased behavioral avoidance. These observations speak to the significant therapeutic potential of mindfulness practice among SLE patients. With its emphasis on acceptance of negative physical and emotional states, mindfulness practice is a promising treatment option, which needs to be further studied. Copyright © 2016. Published by Elsevier Ltd.

Human rhinovirus and disease severity in children.

PubMed

Costa, Lourenço Faria; Queiróz, Divina Aparecida Oliveira; Lopes da Silveira, Hélio; Bernardino Neto, Morun; de Paula, Nayhanne Tizzo; Oliveira, Thelma Fátima Mattos Silva; Tolardo, Aline Lavado; Yokosawa, Jonny

2014-02-01

To evaluate retrospectively human rhinovirus (HRV) infections in children up to 5 years old and factors involved in disease severity. Nasopharyngeal aspirates from 434 children presenting a broad range of respiratory infection symptoms and severity degrees were tested for presence of HRV and 8 other respiratory viruses. Presence of host risk factors was also assessed. HRV was detected in 181 (41.7%) samples, in 107 of them as the only agent and in 74 as coinfections, mostly with respiratory syncytial virus (RSV; 43.2%). Moderate to severe symptoms were observed in 28.9% (31/107) single infections and in 51.3% (38/74) coinfections (P = .004). Multivariate analyses showed association of coinfections with lower respiratory tract symptoms and some parameters of disease severity, such as hospitalization. In coinfections, RSV was the most important virus associated with severe disease. Prematurity, cardiomyopathies, and noninfectious respiratory diseases were comorbidities that also were associated with disease severity (P = .007). Our study showed that HRV was a common pathogen of respiratory disease in children and was also involved in severe cases, causing symptoms of the lower respiratory tract. Severe disease in HRV infections were caused mainly by presence of RSV in coinfections, prematurity, congenital heart disease, and noninfectious respiratory disease.

Indigenous knowledge of pastoralists on respiratory diseases of camels in northern Kenya.

PubMed

Wako, D D; Younan, M; Tessema, T S; Glücks, I V; Baumann, M P O

2016-08-01

The camel disease terminology of pastoralists in northern Kenya differentiates between two respiratory disease complexes of camels. Participatory epidemiology data were collected in 2011 in three camel keeping communities (Gabra, Garri, and Somali) and analysed to assess the validity of this differentiation. Further queries assessed recurrence of the disease in the same animal, most affected age group, relative frequency of occurrence, morbidity rates, mortality rates and response to antibiotic treatment. Based on matrix scoring the cardinal symptom nasal discharge was significantly correlated with Respiratory Disease Complex 1 (RDC1; Somali Hergeb, Gabra & Garri Furri) while cough was correlated with Respiratory Disease Complex 2 (RDC2; Somali Dhuguta, Gabra Qufa, Garri Dhugud). RDC1 appears to occur regularly every year and does not respond to antibiotic treatments while outbreaks of RDC2 are only observed at intervals of several years and treated cases do generally respond to antibiotics. While RDC1 is more severe in calves, RDC 2 is mostly associated with respiratory disease in adults. Elements of this differentiation appear to be in agreement with other authors who differentiate between camel influenza (PI3 virus) and bacterial camel pneumonia, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity.

PubMed

Garcia-Martin, Elena; Rodriguez-Mena, Diego; Satue, Maria; Almarcegui, Carmen; Dolz, Isabel; Alarcia, Raquel; Seral, Maria; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E

2014-02-04

To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity.

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

PubMed

Levy, R; Gérard, L; Kuemmerle-Deschner, J; Lachmann, H J; Koné-Paut, I; Cantarini, L; Woo, P; Naselli, A; Bader-Meunier, B; Insalaco, A; Al-Mayouf, S M; Ozen, S; Hofer, M; Frenkel, J; Modesto, C; Nikishina, I; Schwarz, T; Martino, S; Meini, A; Quartier, P; Martini, A; Ruperto, N; Neven, B; Gattorno, M

2015-11-01

To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Does Family History of Obesity, Cardiovascular, and Metabolic Diseases Influence Onset and Severity of Childhood Obesity?

PubMed

Corica, Domenico; Aversa, Tommaso; Valenzise, Mariella; Messina, Maria Francesca; Alibrandi, Angela; De Luca, Filippo; Wasniewska, Malgorzata

2018-01-01

The objectives were to evaluate (1) the metabolic profile and cardiometabolic risk in overweight/obese children at first assessment, stratifying patients according to severity of overweight and age; and (2) to investigate the relationship between family history (FH) for obesity and cardiometabolic diseases and severity of childhood obesity. In this cross-sectional, retrospective, observational study, 260 children (139 female), aged between 2.4 and 17.2 years, with overweight and obesity were recruited. Data regarding FH for obesity and cardiometabolic diseases were collected. Each patient underwent clinical and auxological examination and fasting blood sampling for metabolic profile. Homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride-to-high-density lipoprotein cholesterol ratio, and atherogenic index of plasma were calculated. To evaluate the severity of obesity, children were divided into two groups for BMI standard deviation (SD) ≤2.5 and BMI SD >2.5. Moreover, study population was analyzed, dividing it into three groups based on the chronological age of patient (<8, 8-11, >11 years). BMI SD was negatively correlated with chronological age ( p  < 0.005) and significantly higher in the group of children <8 years. BMI SD was positively associated with FH for obesity. Patients with more severe obesity (BMI SD >2.5) were younger ( p  < 0.005), mostly prepubertal, presented a significantly higher HOMA-IR ( p  = 0.04), and had a significantly higher prevalence of FH for arterial hypertension, type 2 diabetes mellitus, and coronary heart disease than the other group. (1) Family history of obesity and cardiometabolic diseases are important risk factors for precocious obesity onset in childhood and are related to the severity of obesity. (2) Metabolic profile, especially HOMA-IR, is altered even among the youngest obese children at first evaluation. (3) Stratification of obesity severity, using BMI SD, is effective to estimate the cardiometabolic risk of patients.

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.

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

Analysis of recently identified prostate cancer susceptibility loci in a population-based study: Associations with family history and clinical features

PubMed Central

FitzGerald, Liesel M.; Kwon, Erika M.; Koopmeiners, Joseph S.; Salinas, Claudia A.; Stanford, Janet L.; Ostrander, Elaine A.

2009-01-01

Purpose Two recent genome-wide association studies have highlighted several SNPs purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and clinicopathological features of disease. Experimental Design We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk and stratified by family history of prostate cancer and clinicopathological features of disease was calculated using logistic and polytomous regression. Results These results confirm the importance of multiple previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude to that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, while risk estimates for rs10993994 and rs5945619 varied by Gleason score. Conclusions Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features. PMID:19366831

Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan

PubMed Central

Ku, Li-Jung Elizabeth; Pai, Ming-Chyi; Shih, Pei-Yu

2016-01-01

Objective 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. Methods 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. Results 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. Conclusions 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. PMID:26859891

Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005-2011.

PubMed

Pathak, Ram D; Schroeder, Emily B; Seaquist, Elizabeth R; Zeng, Chan; Lafata, Jennifer Elston; Thomas, Abraham; Desai, Jay; Waitzfelder, Beth; Nichols, Gregory A; Lawrence, Jean M; Karter, Andrew J; Steiner, John F; Segal, Jodi; O'Connor, Patrick J

2016-03-01

Appropriate glycemic control is fundamental to diabetes care, but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia. We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) network sites. Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age, sex, comorbidity status, antecedent A1C level, and medication use. Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years. Rates of severe hypoglycemia were higher among those with older age, chronic kidney disease, congestive heart failure, cardiovascular disease, depression, and higher A1C levels, and in users of insulin, insulin secretagogues, or β-blockers (P < 0.001 for all). Changes in severe hypoglycemia occurrence over time were not clinically significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease, congestive heart failure, and cardiovascular disease. Risk of severe hypoglycemia in clinical settings is considerably higher in identifiable patient subgroups than in randomized controlled trials. Strategies that reduce the risk of hypoglycemia in high-risk patients are needed. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Haemoglobin Levels in Acute Coronary Syndrome Patients Admitted in Cardiology Intensive Care Units in a Tertiary Care Hospital.

PubMed

Naqvil, Syed Mujtaba Hussain; Rao, T Ramesh Kumar; Chandra, Shobha Jagdish

2015-06-01

Epidemiology of abnormal haemoglobin levels and its association with severity of coronary artery disease in Indian patients is uncertain. This prospective observational study was conducted to determine the haemoglobin levels in acute coronary syndrome (ACS) patients and the association of anaemia with the severity of coronary artery disease (CAD) on coronary angiography (CAG). The patients diagnosed with ACS (ST-elevated and non-elevated MI, unstable angina) based on ECG and cardiac enzymes and admitted in cardiology ICU were enrolled in the study after fulfilling study criteria and the baseline haemoglobin level was recorded. The severity of coronary disease of patients who underwent coronary angiography was recorded. A total of 162 patients were enrolled for the study. The overall haemoglobin of patients was 11.99 ± 2.24 g/dl with 12.46 ± 2.33 g/dl in males and 11.17 ± 1.82 g/dl in females (p < 0.05). Anaemia was found in 62.96% patients with no significant gender difference (p > 0.05), however abnormal haemoglobin level (Hb > 16g/dl) was found exclusively in 7.7% males. One hundred one patients underwent coronary angiography and anaemia was present in 60 patients (58.82%) and absent in 41 (40.59%). The difference in mean haemoglobin levels in anaemic patients with single, double, and triple vessel disease was significant (p < 0.05) and corresponding levels in non-anaemic patients were insignificant (p > 0.05). A weak correlation was observed between the haemoglobin level of patients and the percentage of obstruction in CAG (r = 0.26). The odds of having triple vessel disease in anaemic patient are 1.77 (95% CI 0.71 to 4.43). However, the association between anaemia and the severity of coronary artery disease was statistically found to be non-significant. The mean haemoglobin levels decreased as the severity of CAD increased in CAG, however the association was not established between anaemia and the severity of coronary artery disease statistically.

The value of patient registries in advancing pediatric surgical care.

PubMed

Skarsgard, Erik D

2018-05-01

Pediatric surgeons treat a variety of conditions that are distinguished by their low occurrence rate, complexity, and need for integrated multidisciplinary care. Although randomized controlled trials (RCTs) are considered the gold standard for generating evidence to inform best practice, they are poorly suited to rare diseases based on the variability of illness severity, unpredictability in clinical course, and the impact limitations of studying a single intervention at a time. An alternative to RCTs for comparative effectiveness research for rare diseases in pediatric surgery is the patient registry, which collects detailed and condition-specific patient level data related to illness severity, treatment, and outcome, and allows a large, disease-specific database to be created for the dual purposes of collaborative research and quality improvement across participating sites. This review discusses the various functions of a patient registry in fulfilling its mandate of evidence-based practice and outcome improvement using examples from a variety of existing pediatric surgical registries. The value proposition of patient registries as sources of knowledge, facilitators of practice standardization, and enablers of continuous quality improvement is discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

The development of biomarkers for degenerative musculoskeletal conditions.

PubMed

Jayabalan, Prakash; Sowa, Gwendolyn A

2014-02-01

With an aging population, degenerative musculoskeletal conditions will become more prevalent with significantly increasing costs to society over the next several decades. The majority of these conditions are diagnosed radiographically, at which point the disease process is often more advanced and challenging to treat. The commonly available radiographic studies also do not adequately provide information as to the exact pain generator and findings often do not correlate either to patient symptoms or function. Personalized medicine involves formulating treatments based on a patient's own biology. The development of biological markers (biomarkers) pertaining to disease is a rapidly growing area within this field of medicine. For degenerative musculoskeletal conditions, biomarkers have the potential to provide an early non-invasive method of assessing the location and severity of tissue damage and presence of inflammation. By outlining mechanisms of disease they could allow the formulation of further treatment targets and through sub-categorizing patients into different groups based on their biomarker profile, one could provide more efficacious treatments for patients. The present article is a review of the development of biomarkers for these purposes specifically as they pertain to degenerative musculoskeletal conditions.

Prognosis elements in surgical treatment of complicated umbilical hernia in patients with liver cirrhosis.

PubMed

Banu, P; Popa, F; Constantin, V D; Bălălău, C; Nistor, M

2013-09-15

The surgical treatment of umbilical hernia in cirrhosis patients raises special management challenges. The attitude upon the repair of these hernias varies from expectancy or elective treatment in early stages of the disease to the surgical treatment only if complications occur. We have assessed 22 consecutive cases of cirrhosis patients treated for complicated umbilical hernia in the Surgical Department of "Sf. Pantelimon" Emergency Hospital in Bucharest between January 2008 and December 2012. The patients' stratification was done in stages of liver disease based upon Child-Pugh classification. Complications that required emergency repair were the following: strangulation, incarceration and hernia rupture. The postoperative complications were ordered in five grades of severity based upon Clavien classification. The severity of the complications was higher in advanced stages of liver cirrhosis, Child B and C. There were 5 deaths representing 22,7%, four of them in patients with Child C disease stage. The incidence of morbidity and mortality after umbilical hernia repair in emergencies increases in advanced stages of liver cirrhosis. It is advisable to prevent complications occurrence and perform surgical repair of umbilical hernia in elective condition.

Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in Indonesia.

PubMed

Utama, Andi; Tania, Navessa Padma; Dhenni, Rama; Gani, Rino Alvani; Hasan, Irsan; Sanityoso, Andri; Lelosutan, Syafruddin A R; Martamala, Ruswhandi; Lesmana, Laurentius Adrianus; Sulaiman, Ali; Tai, Susan

2010-09-01

Hepatitis C virus (HCV) genotype distribution in Indonesia has been reported. However, the identification of HCV genotype was based on 5'-UTR or NS5B sequence. This study was aimed to observe HCV core sequence variation among HCV-associated liver disease patients in Jakarta, and to analyse the HCV genotype diversity based on the core sequence. Sixty-eight chronic hepatitis (CH), 48 liver cirrhosis (LC) and 34 hepatocellular carcinoma (HCC) were included in this study. HCV core variation was analysed by direct sequencing. Alignment of HCV core sequences demonstrated that the core sequence was relatively varied among the genotype. Indeed, 237 bases of the core sequence could classify the HCV subtype; however, 236 bases failed to differentiate several subtypes. Based on 237 bases of the core sequences, the HCV strains were classified into genotypes 1 (subtypes 1a, 1b and 1c), 2 (subtypes 2a, 2e and 2f) and 3 (subtypes 3a and 3k). The HCV 1b (47.3%) was the most prevalent, followed by subtypes 1c (18.7%), 3k (10.7%), 2a (10.0%), 1a (6.7%), 2e (5.3%), 2f (0.7%) and 3a (0.7%). HCV 1b was the most common in all patients, and the prevalence increased with the severity of liver disease (36.8% in CH, 54.2% in LC and 58.8% in HCC). These results were similar to a previous report based on NS5B sequence analysis. Hepatitis C virus core sequence (237 bases) could identify the HCV subtype and the prevalence of HCV subtype based on core sequence was similar to those based on the NS5B region.

Ovine pedomics: the first study of the ovine foot 16S rRNA-based microbiome

USDA-ARS?s Scientific Manuscript database

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Ovine foot rot is an infectious, contagious disease of sheep that causes severe lameness and economic loss from decreased flock produc...

The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

PubMed

Bedi, Pallavi; Chalmers, James D; Goeminne, Pieter C; Mai, Cindy; Saravanamuthu, Pira; Velu, Prasad Palani; Cartlidge, Manjit K; Loebinger, Michael R; Jacob, Joe; Kamal, Faisal; Schembri, Nicola; Aliberti, Stefano; Hill, Uta; Harrison, Mike; Johnson, Christopher; Screaton, Nicholas; Haworth, Charles; Polverino, Eva; Rosales, Edmundo; Torres, Antoni; Benegas, Michael N; Rossi, Adriano G; Patel, Dilip; Hill, Adam T

2018-05-01

The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV 1 , sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV 1 , 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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.

Plant-based oral vaccines against zoonotic and non-zoonotic diseases.

PubMed

Shahid, Naila; Daniell, Henry

2016-11-01

The shared diseases between animals and humans are known as zoonotic diseases and spread infectious diseases among humans. Zoonotic diseases are not only a major burden to livestock industry but also threaten humans accounting for >60% cases of human illness. About 75% of emerging infectious diseases in humans have been reported to originate from zoonotic pathogens. Because antibiotics are frequently used to protect livestock from bacterial diseases, the development of antibiotic-resistant strains of epidemic and zoonotic pathogens is now a major concern. Live attenuated and killed vaccines are the only option to control these infectious diseases and this approach has been used since 1890. However, major problems with this approach include high cost and injectable vaccines is impractical for >20 billion poultry animals or fish in aquaculture. Plants offer an attractive and affordable platform for vaccines against animal diseases because of their low cost, and they are free of attenuated pathogens and cold chain requirement. Therefore, several plant-based vaccines against human and animals diseases have been developed recently that undergo clinical and regulatory approval. Plant-based vaccines serve as ideal booster vaccines that could eliminate multiple boosters of attenuated bacteria or viruses, but requirement of injectable priming with adjuvant is a current limitation. So, new approaches like oral vaccines are needed to overcome this challenge. In this review, we discuss the progress made in plant-based vaccines against zoonotic or other animal diseases and future challenges in advancing this field. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Is periodontal disease a public health problem?

PubMed

Batchelor, P

2014-10-01

Clinically defined periodontal disease is highly prevalent, has considerable impacts on individuals and society and is costly to treat; the cost of dental care is the fourth highest costs of all diseases and consuming between 5 and 10% of all healthcare resources. Changes in the epidemiology of clinically defined periodontal diseases suggest that the prevalence of severe periodontal disease is low and rates of progression of periodontal destruction tend to be relatively slow. Current periodontal care modalities have a remarkably weak evidence base, with considerable resources allocated to fund interventions that include oral hygiene instruction, scale and polishes through to surgical interventions. The public health problem lies more in the failure in design of a contract between dental professionals and the state. Such a contract needs to recognise both the wider determinants of disease and the role that dental professionals could play: a contract that concentrated on rewarding outcomes, namely a diminution in treatment need, as opposed to one based simply on the number of interventions would be a major step forward.

Fully automated disease severity assessment and treatment monitoring in retinopathy of prematurity using deep learning

NASA Astrophysics Data System (ADS)

Brown, James M.; Campbell, J. Peter; Beers, Andrew; Chang, Ken; Donohue, Kyra; Ostmo, Susan; Chan, R. V. Paul; Dy, Jennifer; Erdogmus, Deniz; Ioannidis, Stratis; Chiang, Michael F.; Kalpathy-Cramer, Jayashree

2018-03-01

Retinopathy of prematurity (ROP) is a disease that affects premature infants, where abnormal growth of the retinal blood vessels can lead to blindness unless treated accordingly. Infants considered at risk of severe ROP are monitored for symptoms of plus disease, characterized by arterial tortuosity and venous dilation at the posterior pole, with a standard photographic definition. Disagreement among ROP experts in diagnosing plus disease has driven the development of computer-based methods that classify images based on hand-crafted features extracted from the vasculature. However, most of these approaches are semi-automated, which are time-consuming and subject to variability. In contrast, deep learning is a fully automated approach that has shown great promise in a wide variety of domains, including medical genetics, informatics and imaging. Convolutional neural networks (CNNs) are deep networks which learn rich representations of disease features that are highly robust to variations in acquisition and image quality. In this study, we utilized a U-Net architecture to perform vessel segmentation and then a GoogLeNet to perform disease classification. The classifier was trained on 3,000 retinal images and validated on an independent test set of patients with different observed progressions and treatments. We show that our fully automated algorithm can be used to monitor the progression of plus disease over multiple patient visits with results that are consistent with the experts' consensus diagnosis. Future work will aim to further validate the method on larger cohorts of patients to assess its applicability within the clinic as a treatment monitoring tool.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach.

PubMed

Cuadrado, Antonio; Manda, Gina; Hassan, Ahmed; Alcaraz, María José; Barbas, Coral; Daiber, Andreas; Ghezzi, Pietro; León, Rafael; López, Manuela G; Oliva, Baldo; Pajares, Marta; Rojo, Ana I; Robledinos-Antón, Natalia; Valverde, Angela M; Guney, Emre; Schmidt, Harald H H W

2018-04-01

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases. Copyright © 2018 by The Author(s).

Patterns of Dupuytren disease in fingers: studying correlations with a multivariate ordinal logit model.

PubMed

Lanting, Rosanne; Nooraee, Nazanin; Werker, Paul M N; van den Heuvel, Edwin R

2014-09-01

Dupuytren disease affects fingers in a variable fashion. Knowledge about specific disease patterns (phenotype) based on location and severity of the disease is lacking. In this cross-sectional study, 344 primary affected hands with Dupuytren disease were physically examined. The Pearson correlation coefficient between the coexistence of Dupuytren disease in pairs of fingers was calculated, and agglomerative hierarchical clustering was applied to identify possible clusters of affected fingers. With a multivariate ordinal logit model, the authors studied the correlation on severity, taking into account age and sex, and tested hypotheses on independence between groups of fingers. The ring finger was most frequently affected by Dupuytren disease, and contractures were seen in 15.1 percent of affected rays. The severity of thumb and index finger, middle and ring fingers, and middle and little fingers was significantly correlated. Occurrences in pairs of fingers were highest in the middle and ring fingers and lowest in the thumb and index finger. Correlation between the ring and little fingers and a correlation between fingers from the ulnar and radial sides could not be demonstrated. Rays on the ulnar side of the hand are predominantly affected. The middle finger is substantially correlated with other fingers on the ulnar side, and the thumb and index finger are correlated; however, there was no evidence that the ulnar side and the radial side were correlated in any way, which suggests that occurrence on one side of the hand does not predict Dupuytren disease on the other side of the hand. Risk, III.

Prevalence and predictors for periodontitis among adults in China, 2010

PubMed Central

Zhang, Qi; Li, Zhixin; Wang, Chunxiao; Shen, Tao; Yang, Yang; Chotivichien, Saipin; Wang, Linhong

2014-01-01

Background Although the interrelationship between poor oral health and chronic diseases is well established, few related studies are available in China. In this study, the prevalence of severe periodontitis and its association with chronic diseases among adults in China have been explored. Design During China's 2010 Chronic Disease and Risk Factor Surveillance (CCDRFS) survey among adults aged 18 and older, 3 out of 162 surveillance points and the entire sample from each point (600×3=1,800 subjects) were selected as pilot study sites in which oral examination was performed. Basic demographic information, chronic diseases status, and results of oral examination were collected from 2010 CCDRFS data. A standard oral examination was conducted by trained staff. Periodontitis was defined as moderate (4–5 mm pockets) or severe (≥6 mm pockets). Chronic disease status was determined by using standard methods and criteria. Multivariate logistic analysis was used to identify the independent association of various factors with severe periodontitis. Results Of 1,800 subjects, 1,728 subjects (96%) provided complete information. The prevalence of severe periodontitis was 1.9% (32/1,728) (95% CI=1.2–2.5). In multivariate model, participants with diabetes were 2.4 times (OR=2.4, 95% CI=1.1–5.6) more likely to have severe periodontitis. Being male was significantly associated with severe periodontitis (OR=3.5, 95% CI=1.6–7.7). Living in a rural area was related to an increased chance of having severe periodontitis (OR=2.1, 95% CI=1.0– 4.9). Attainment of at least 6 years of education was inversely associated with severe periodontitis (OR=0.3, 95% CI=0.1–0.8). Conclusions According to this pilot project, prevalence of severe periodontitis was low. Control measures should be particularly emphasized for high-risk groups such as less educated people (<6 years of education), people living in rural areas, men, and diabetes patients. Population-based studies, including oral examination by trained staff, are feasible and should be done in order to understand the burden of periodontitis and to provide an effective response to this key oral health issue. PMID:25008055

The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology.

PubMed

Sadatsafavi, Mohsen; Xie, Hui; Etminan, Mahyar; Johnson, Kate; FitzGerald, J Mark

2018-01-01

There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course. Previous studies on this topic did not generate causally-interpretable estimates. Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients. Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes. We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events. Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics. 35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up. The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations. This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality. There was substantial heterogeneity in the individual-specific rate of severe exacerbations. Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile. Using robust statistical methodology that controlled for heterogeneity in exacerbation rates among individuals, we demonstrated potential causal associations among past and future severe exacerbations, albeit the magnitude of association was noticeably lower than previously reported. The prevention of severe exacerbations has the potential to modify the disease trajectory.

Research on Hygiene Based on Fieldwork and Experimental Studies.

PubMed

Yajima, Ichiro

2017-01-01

Several experimental studies on hygiene have recently been performed and fieldwork studies are also important and essential tools. However, the implementation of experimental studies is insufficient compared with that of fieldwork studies on hygiene. Here, we show our well-balanced implementation of both fieldwork and experimental studies of toxic-element-mediated diseases including skin cancer and hearing loss. Since the pollution of drinking well water by toxic elements induces various diseases including skin cancer, we performed both fieldwork and experimental studies to determine the levels of toxic elements and the mechanisms behind the development of toxic-element-related diseases and to develop a novel remediation system. Our fieldwork studies in several countries including Bangladesh, Vietnam and Malaysia demonstrated that drinking well water was polluted with high concentrations of several toxic elements including arsenic, barium, iron and manganese. Our experimental studies using the data from our fieldwork studies demonstrated that these toxic elements caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system that adsorbs toxic elements from polluted drinking water. A well-balanced implementation of both fieldwork and experimental studies is important for the prediction, prevention and therapy of toxic-element-mediated diseases.

Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal †

PubMed Central

Peres, Gonçalo Miguel; Mariana, Melissa

2018-01-01

Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment. PMID:29367581

A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets

PubMed Central

Sanjak, Jaleal S.; Long, Anthony D.; Thornton, Kevin R.

2017-01-01

The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation. PMID:28103232

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.

Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: Middle East/North Africa regional consensus on prevention, diagnosis and management.

PubMed

Al Jefri, A H; Abujazar, H; Al-Ahmari, A; Al Rawas, A; Al Zahrani, Z; Alhejazi, A; Bekadja, M A; Ibrahim, A; Lahoucine, M; Ousia, S; Bazarbachi, A

2017-04-01

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is a serious, early complication of haematopoietic stem cell transplantation (HSCT), severe and very severe forms of which are associated with a high mortality rate. A wide variety of patient, disease and treatment-related risk factors for VOD/SOS have been identified. Several bodies have published recommendations for the diagnosis, prevention and management of VOD/SOS following HSCT. A group of regional experts have developed a consensus statement on the diagnosis, prevention and management of VOD/SOS in the Middle East and North Africa region to help in the management of HSCT patients in the region. Risk factors of particular relevance in the region include iron overload in thalassaemia patients, some hereditary metabolic disorders due to consanguinity and infection with hepatitis virus B or C. Recommendations include diagnosis of VOD/SOS based on established clinical criteria, prophylaxis with defibrotide and/or ursodeoxycholic acid in patients at increased risk of VOD/SOS, and treatment with defibrotide for patients with severe/very severe VOD/SOS (and, if clinically indicated, in those with moderate or rapidly progressing VOD/SOS, as per the new European Society for Blood and Marrow Transplantation classification).

Education to improve quality of life of people with chronic inflammatory skin conditions: a systematic review of the evidence.

PubMed

Pickett, K; Frampton, G; Loveman, E

2016-06-01

Patient and carer education has been proposed as a way of improving health-related quality of life (HRQoL) among people with chronic inflammatory skin conditions. This systematic review aimed to assess the effects of education that specifically addresses HRQoL among people with chronic inflammatory skin conditions. We searched 12 literature databases and other sources (up to July 2014). Seven randomized controlled trials (RCTs) met the review inclusion criteria. Data from these RCTs were extracted and critically appraised. Two RCTs showed that for psoriasis in adults, group-based and text message education (as adjuncts to usual care) resulted in better HRQoL and disease severity outcomes than comparators, respectively. One RCT found that group-based education for children with eczema (atopic dermatitis) and their parents resulted in greater improvements in parents' HRQoL and in the children's disease severity than no education at 12 months. The remaining RCTs evaluated an educational session for psoriasis, a website for carers of children with eczema, information on skincare and make-up use given to women with acne, and an itch-coping programme for a range of conditions, all as adjuncts to usual care. None of these RCTs found statistically significant effects on HRQoL or disease severity compared with usual care. Common features of the effective interventions were long delivery (over 6 weeks to 3 months) and delivery by a multidisciplinary team. Overall, the evidence base is currently limited and generally has an unclear risk of bias. There is a need for more large RCTs evaluating piloted and theory-based interventions. © 2016 Crown copyright. British Journal of Dermatology © 2016 British Association of Dermatologists This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Human genetics of infectious diseases: a unified theory

PubMed Central

Casanova, Jean-Laurent; Abel, Laurent

2007-01-01

Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

Prediction and Informative Risk Factor Selection of Bone Diseases.

PubMed

Li, Hui; Li, Xiaoyi; Ramanathan, Murali; Zhang, Aidong

2015-01-01

With the booming of healthcare industry and the overwhelming amount of electronic health records (EHRs) shared by healthcare institutions and practitioners, we take advantage of EHR data to develop an effective disease risk management model that not only models the progression of the disease, but also predicts the risk of the disease for early disease control or prevention. Existing models for answering these questions usually fall into two categories: the expert knowledge based model or the handcrafted feature set based model. To fully utilize the whole EHR data, we will build a framework to construct an integrated representation of features from all available risk factors in the EHR data and use these integrated features to effectively predict osteoporosis and bone fractures. We will also develop a framework for informative risk factor selection of bone diseases. A pair of models for two contrast cohorts (e.g., diseased patients versus non-diseased patients) will be established to discriminate their characteristics and find the most informative risk factors. Several empirical results on a real bone disease data set show that the proposed framework can successfully predict bone diseases and select informative risk factors that are beneficial and useful to guide clinical decisions.

[Inpatients days in patients with respiratory diseases and periodontal disease].

PubMed

Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; González-Cruz, Herminia; Casa-Medina, Guillermo; García-Sancho, Cecilia

2017-01-01

Periodontal disease is a chronic inflammatory gingival process that has been associated with the severity of respiratory diseases. In Mexico a prevalence of 78% was found in population with social security and > 60 years old. The aim of this study is to establish the association between periodontal disease and respiratory diseases according to the inpatient days. A cross-sectional study was conducted from January to December 2011. We included hospitalized patients, ≥ 18 years of age, without sedation or intubated. A dentist classified patients into two groups according to the severity of the periodontal disease: mild-to-moderate and severe. We estimated medians of inpatient days by disease and severity. Negative binomial models were adjusted to estimate incidence rate ratios and predicted inpatient days. 3,059 patients were enrolled. The median of observed and predicted inpatient days was higher in the group of severe periodontal disease (p < 0.05). Patients with chronic obstructive pulmonary disease, tuberculosis, and influenza had the highest incidence rates ratios of periodontal disease (p < 0.05). The severity of periodontal disease is positively -associated with inpatient days of patients with respiratory diseases.

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.

Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study.

PubMed

Hegvik, Tor-Arne; Instanes, Johanne Telnes; Haavik, Jan; Klungsøyr, Kari; Engeland, Anders

2018-05-01

Several studies have demonstrated associations between neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), and the immune system, including autoimmune diseases. Since ADHD and many autoimmune diseases show sex-specific properties, such associations may also differ by sex. Using Norwegian national registries, we performed a cross-sectional study based on a cohort of 2,500,118 individuals to investigate whether ADHD is associated with common autoimmune diseases. Associations between ADHD and autoimmune diseases in females and males were investigated with logistic regression and effect modification by sex was evaluated. Several subanalyses were performed. The strongest association was found between ADHD and psoriasis in females, adjusted odds ratio (adjOR) = 1.57 (95% confidence interval: 1.46-1.68) and males, adjOR = 1.31 (1.23-1.40); p value for interaction < 0.0001. Furthermore, among females, ADHD was associated with Crohn's disease, adjOR = 1.44 (1.16-1.79) and ulcerative colitis, adjOR = 1.28 (1.06-1.54). In contrast, males with ADHD had lower odds of Crohn's disease, adjOR = 0.71 (0.54-0.92), in addition to a trend for lower odds of ulcerative colitis, adjOR = 0.86 (0.71-1.03); p values for interaction < 0.0001 and 0.0023, respectively. In a group of females where information on smoking and body mass index was available, adjustment for these potential mediators did not substantially alter the associations. Our findings support previously reported associations between ADHD and diseases of the immune system. The associations differ by sex, suggesting that sex-specific immune-mediated neurodevelopmental processes may be involved in the etiology of ADHD.

The role of bacillus-based biological control agents in integrated pest management systems: plant diseases.

PubMed

Jacobsen, B J; Zidack, N K; Larson, B J

2004-11-01

ABSTRACT Bacillus-based biological control agents (BCAs) have great potential in integrated pest management (IPM) systems; however, relatively little work has been published on integration with other IPM management tools. Unfortunately, most research has focused on BCAs as alternatives to synthetic chemical fungicides or bactericides and not as part of an integrated management system. IPM has had many definitions and this review will use the national coalition for IPM definition: "A sustainable approach to managing pests by combining biological, cultural, physical and chemical tools in a way that minimizes economic, health and environmental risks." This review will examine the integrated use of Bacillus-based BCAs with disease management tools, including resistant cultivars, fungicides or bactericides, or other BCAs. This integration is important because the consistency and degree of disease control by Bacillus-based BCAs is rarely equal to the control afforded by the best fungicides or bactericides. In theory, integration of several tools brings stability to disease management programs. Integration of BCAs with other disease management tools often provides broader crop adaptation and both more efficacious and consistent levels of disease control. This review will also discuss the use of Bacillus-based BCAs in fungicide resistance management. Work with Bacillus thuringiensis and insect pest management is the exception to the relative paucity of reports but will not be the focus of this review.

Survival after initial diagnosis of Alzheimer disease.

PubMed

Larson, Eric B; Shadlen, Marie-Florence; Wang, Li; McCormick, Wayne C; Bowen, James D; Teri, Linda; Kukull, Walter A

2004-04-06

Alzheimer disease is an increasingly common condition in older people. Knowledge of life expectancy after the diagnosis of Alzheimer disease and of associations of patient characteristics with survival may help planning for future care. To investigate the course of Alzheimer disease after initial diagnosis and examine associations hypothesized to correlate with survival among community-dwelling patients with Alzheimer disease. Prospective observational study. An Alzheimer disease patient registry from a base population of 23 000 persons age 60 years and older in the Group Health Cooperative, Seattle, Washington. 521 newly recognized persons with Alzheimer disease enrolled from 1987 to 1996 in an Alzheimer disease patient registry. Baseline measurements included patient demographic features, Mini-Mental State Examination score, Blessed Dementia Rating Scale score, duration since reported onset of symptoms, associated symptoms, comorbid conditions, and selected signs. Survival was the outcome of interest. The median survival from initial diagnosis was 4.2 years for men and 5.7 years for women with Alzheimer disease. Men had poorer survival across all age groups compared with females. Survival was decreased in all age groups compared with the life expectancy of the U.S. population. Predictors of mortality based on proportional hazards models included a baseline Mini-Mental State Examination score of 17 or less, baseline Blessed Dementia Rating Scale score of 5.0 or greater, presence of frontal lobe release signs, presence of extrapyramidal signs, gait disturbance, history of falls, congestive heart failure, ischemic heart disease, and diabetes at baseline. The base population, although typical of the surrounding Seattle community, may not be representative of other, more diverse populations. In this sample of community-dwelling elderly persons who received a diagnosis of Alzheimer disease, survival duration was shorter than predicted on the basis of U.S. population data, especially for persons with onset at relatively younger ages. Features significantly associated with reduced survival at diagnosis were increased severity of cognitive impairment, decreased functional level, history of falls, physical examination findings of frontal release signs, and abnormal gait. The variables most strongly associated with survival were measures of disease severity at the time of diagnosis. These results should be useful to patients and families experiencing Alzheimer disease, other caregivers, clinicians, and policymakers when planning for future care needs.

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

PubMed Central

Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Bammler, Theo K.; Stewart, Tessandra; Zabetian, Cyrus P.; Peskind, Elaine R.; Hu, Shu-Ching; Quinn, Joseph F.; Galasko, Douglas R.; Zhang, Jing

2015-01-01

Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ∼14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038)j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. PMID:25556233

Treatments for Severe Cutaneous Adverse Reactions

PubMed Central

Cho, Yung-Tsu

2017-01-01

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations. PMID:29445753

Oxidative Stress, Nitric Oxide, and Diabetes

PubMed Central

Pitocco, Dario; Zaccardi, Francesco; Di Stasio, Enrico; Romitelli, Federica; Santini, Stefano A.; Zuppi, Cecilia; Ghirlanda, Giovanni

2010-01-01

In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients. PMID:20703435

Plantar pressures in children with and without sever's disease.

PubMed

Becerro de Bengoa Vallejo, Ricardo; Losa Iglesias, Marta Elena; Rodríguez Sanz, David; Prados Frutos, Juan Carlos; Salvadores Fuentes, Paloma; Chicharro, José López

2011-01-01

a case-control study was conducted to compare static plantar pressures and distribution of body weight across the two lower limbs, as well as the prevalence of gastrocnemius soleus equinus, in children with and without calcaneal apophysitis (Sever's disease). the participants were 54 boys enrolled in a soccer academy, of which eight were lost to follow-up. Twenty-two boys with unilateral Sever's disease comprised the Sever's disease group and 24 healthy boys constituted a control group. Plantar pressure data were collected using pedobarography, and gastrocnemius soleus equinus was assessed. peak pressure and percentage of body weight supported were significantly higher in the symptomatic feet of the Sever's disease group than in the asymptomatic feet of the Sever's disease group and the control group. Every child in the Sever's disease group had bilateral gastrocnemius equinus, while nearly all children in the control group had no equinus. high plantar foot pressures are associated with Sever's disease, although it is unclear whether they are a predisposing factor or a result of the condition. Gastrocnemius equinus may be a predisposing factor for Sever's disease. Further research is needed to identify other factors involved in the disease and to better understand the factors that contribute to abnormal distribution of body weight in the lower limbs.

Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

PubMed Central

2016-01-01

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose. PMID:27721835

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa.

PubMed

von Mollendorf, Claire; Tempia, Stefano; von Gottberg, Anne; Meiring, Susan; Quan, Vanessa; Feldman, Charles; Cloete, Jeane; Madhi, Shabir A; O'Brien, Katherine L; Klugman, Keith P; Whitney, Cynthia G; Cohen, Cheryl

2017-01-01

Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005-2008) and post-PCV introduction (2012-2013) in children aged 0-59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000-140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000-50,000) severe pneumococcal disease cases were estimated in 2012-2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000-6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000-2500) in 2012-2013, a mortality rate difference of 61 per 100,000 child-years. While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0-59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.

Proposal of diagnostic process model for computer based diagnosis.

PubMed

Matsumura, Yasushi; Takeda, Toshihiro; Manabe, Shiro; Saito, Hirokazu; Teramoto, Kei; Kuwata, Shigeki; Mihara, Naoki

2012-01-01

We aim at making a diagnosis support system that can be put to practical use. We proposed a diagnostic process model based on simple knowledge which can be gleaned from textbooks. We defined clinical finding (CF) as a general concept for patient's symptom or findings etc., whose value is expressed by Boolean. We call the combination of several CFs a "CF pattern", and a set of CF patterns with concomitant diseases "case base". We consider diagnosis as a process of searching an instance from the case base whose CF pattern is concomitant with that of a patient. The diseases which have the same CF pattern are candidates for diagnosis. Then we select a CF which is present in part of the candidates and check whether it is present or absent in the patient in order to narrow down the candidates. Because the case base does not exist in reality, the probability of CF pattern is calculated by the product of CF occurrence rate assuming that occurrence of CF is independent. Therefore the knowledge required for diagnosis is frequency of disease under sex and age group and CF-disease relation (CF and its occurrence rate in the disease). By processing these two types of knowledge, diagnosis can be made.

Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

PubMed

Wolters, Frank L; Joling, Catelijne; Russel, Maurice G; Sijbrandij, Jildou; De Bruin, Marion; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Bodini, Paolo; Ryan, Barbara; O'Morain, Colm; Mouzas, Ioannis A; Tsianos, Epameinondas; Vermeire, Severine; Monteiro, Estela; Limonard, Charles; Vatn, Morten; Fornaciari, Giovanni; Rodriguez, Dolores; Groot, Wim; Moum, Bjørn; Stockbrügger, Reinhold W

2007-03-01

Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

The disease profile of poverty: morbidity and mortality in northern Uganda in the context of war, population displacement and HIV/AIDS.

PubMed

Accorsi, S; Fabiani, M; Nattabi, B; Corrado, B; Iriso, R; Ayella, E O; Pido, B; Onek, P A; Ogwang, M; Declich, S

2005-03-01

The population of Gulu District (northern Uganda) has been severely incapacitated by war, epidemics and social disruption. This study is aimed at describing disease patterns and trends in this area through a retrospective analysis of discharge records for 155205 in-patients of Lacor Hospital in the period 1992-2002. The burden of infectious diseases in childhood is overwhelming, with malaria accounting for the steepest increase in admissions. Admissions for war-related injuries and malnutrition fluctuated with the intensity of the war and the severity of famine. Emerging and re-emerging infections, such as HIV/AIDS, tuberculosis and Ebola, accounted for a heavy disease burden; however, there has been a trend for admissions related to HIV/AIDS and tuberculosis to decrease since the implementation of community-based services. Vulnerable groups (infants, children and women) accounted for 79.8% of admissions. Long-term war, population displacement, the collapse of social structures and the breakdown of the health system place people at a much greater risk of persistent, emerging and re-emerging infectious diseases, malnutrition and war-related injuries, shaping the 'disease profile of poverty'. Most of the disease burden results from infectious diseases of childhood, whose occurrence could be dramatically reduced by low-cost and effective preventive and curative interventions.

Timing and severity of immunizing diseases in rabbits is controlled by seasonal matching of host and pathogen dynamics

PubMed Central

Wells, Konstans; Brook, Barry W.; Lacy, Robert C.; Mutze, Greg J.; Peacock, David E.; Sinclair, Ron G.; Schwensow, Nina; Cassey, Phillip; O'Hara, Robert B.; Fordham, Damien A.

2015-01-01

Infectious diseases can exert a strong influence on the dynamics of host populations, but it remains unclear why such disease-mediated control only occurs under particular environmental conditions. We used 16 years of detailed field data on invasive European rabbits (Oryctolagus cuniculus) in Australia, linked to individual-based stochastic models and Bayesian approximations, to test whether (i) mortality associated with rabbit haemorrhagic disease (RHD) is driven primarily by seasonal matches/mismatches between demographic rates and epidemiological dynamics and (ii) delayed infection (arising from insusceptibility and maternal antibodies in juveniles) are important factors in determining disease severity and local population persistence of rabbits. We found that both the timing of reproduction and exposure to viruses drove recurrent seasonal epidemics of RHD. Protection conferred by insusceptibility and maternal antibodies controlled seasonal disease outbreaks by delaying infection; this could have also allowed escape from disease. The persistence of local populations was a stochastic outcome of recovery rates from both RHD and myxomatosis. If susceptibility to RHD is delayed, myxomatosis will have a pronounced effect on population extirpation when the two viruses coexist. This has important implications for wildlife management, because it is likely that such seasonal interplay and disease dynamics has a strong effect on long-term population viability for many species. PMID:25566883

Glycated Hemoglobin (HbA1c) Correlation with Severity of Coronary Artery Disease in Non-diabetic Patients - A Hospital based Study from North-Eastern India

PubMed Central

Dutta, Bornali; Neginhal, Mahesh

2016-01-01

Introduction Glycated Hemoglobin (HbA1c) levels are predictive of cardiovascular disease and mortality in patients with diabetes mellitus, however, association of HbA1c with Coronary Artery Disease (CAD) in non-diabetics is inconsistent. Aim To evaluate the correlation between HbA1c level and severity of CAD in non-diabetic patients using SYNTAX score in a cohort of proven CAD on angiography at Gauhati Medical College, Guwahati, Assam, India, which is a major tertiary care hospital of North-Eastern India. Materials and Methods We prospectively collected data of non-diabetic patients with proven CAD on angiography from June 2014 to June 2015. Patients were divided into four groups (interquartiles) according to HbA1c levels, less than 4.8%, 4.8% to 5.1%, 5.1% to 5.6%, and 5.6% to 6.5%. Severity of CAD was assessed using SYNTAX score and the number of coronary vessels diseased. We compared different quartiles of HbA1c with regard to SYNTAX score and number of diseased vessels. Results A total of 346 patients were included in the study. Mean age was 58.1±10.4 years. Of the total 91.9% (318) were males, 44.8% (155) were hypertensives, 29.2% (101) were smokers and 34.7% (120) were dyslipidemic. We found that CAD severity by SYNTAX score as well as number of vessels involved was significantly different among quartiles (p-values <0.001 and <0.001 respectively). Increase in HbA1c level was strongly correlated with disease severity and higher SYNTAX score. A significant increase was noted in the mean number of diseased vessels (p-value <0.001) as HbA1c level increases. Age, gender, hypertension and dyslipidemia did not show significant difference among quartiles however smoking was found to be an independent predictor of severity of CAD by SYNTAX score (p <0.05). Conclusion From this clinical study, we can conclude that a significant correlation exists between HbA1c and severity of CAD by SYNTAX score as well as number of vessels involved in non- diabetes. PMID:27790487

Early rheumatoid disease. II. Patterns of joint involvement.

PubMed Central

Fleming, A; Benn, R T; Corbett, M; Wood, P H

1976-01-01

Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

A flexible data-driven comorbidity feature extraction framework.

PubMed

Sideris, Costas; Pourhomayoun, Mohammad; Kalantarian, Haik; Sarrafzadeh, Majid

2016-06-01

Disease and symptom diagnostic codes are a valuable resource for classifying and predicting patient outcomes. In this paper, we propose a novel methodology for utilizing disease diagnostic information in a predictive machine learning framework. Our methodology relies on a novel, clustering-based feature extraction framework using disease diagnostic information. To reduce the data dimensionality, we identify disease clusters using co-occurrence statistics. We optimize the number of generated clusters in the training set and then utilize these clusters as features to predict patient severity of condition and patient readmission risk. 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 hospital discharge records and ICD-9-CM codes. The proposed framework is tested on Ronald Reagan UCLA Medical Center Electronic Health Records (EHR) from 3041 Congestive Heart Failure (CHF) patients and the UCI 130-US diabetes dataset that includes admissions from 69,980 diabetic patients. We compare our cluster-based feature set with the commonly used comorbidity frameworks including Charlson's index, Elixhauser's comorbidities and their variations. The proposed approach was shown to have significant gains between 10.7-22.1% in predictive accuracy for CHF severity of condition prediction and 4.65-5.75% in diabetes readmission prediction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene.

PubMed

Wu, Wei-Chi; Drenser, Kimberly; Trese, Michael; Capone, Antonio; Dailey, Wendy

2007-02-01

To correlate the ophthalmic findings of patients with pediatric vitreoretinopathies with mutations occurring in the Norrie disease gene (NDP). One hundred nine subjects with diverse pediatric vitreoretinopathies and 54 control subjects were enrolled in the study. Diagnoses were based on retinal findings at each patient's first examination. Samples of DNA from each patient underwent polymerase chain reaction amplification and direct sequencing of the NDP gene. Eleven male patients expressing mutations in the NDP gene were identified in the test group, whereas the controls demonstrated wild-type NDP. All patients diagnosed as having Norrie disease had mutations in the NDP gene. Four of the patients with Norrie disease had mutations involving a cysteine residue in the cysteine-knot motif. Four patients diagnosed as having familial exudative vitreoretinopathy were found to have noncysteine mutations. One patient with retinopathy of prematurity had a 14-base deletion in the 5' untranslated region (exon 1), and 1 patient with bilateral persistent fetal vasculature syndrome expressed a noncysteine mutation in the second exon. Mutations disrupting the cysteine-knot motif corresponded to severe retinal dysgenesis, whereas patients with noncysteine mutations had varying degrees of avascular peripheral retina, extraretinal vasculature, and subretinal exudate. Patients exhibiting severe retinal dysgenesis should be suspected of carrying a mutation that disrupts the cysteine-knot motif in the NDP gene.

Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727

Study on application of optical clearing technique in skin diseases

NASA Astrophysics Data System (ADS)

Shan, Hao; Liang, Yanmei; Wang, Jingyi; Li, Yan

2012-11-01

So far, the study of the optical clearing is almost always about healthy tissue. However, the ultimate goal is to detect diseases for clinical application. Optical clearing on diseased skins is explored. The effect is evaluated by applying a combined liquid paraffin and glycerol mixed solution on several kinds of diseased skins in vitro. Scanning experiments from optical coherence tomography show that it has different effects among fibroma, pigmented nevus, and seborrheic keratosis. Based on the results, we conclude that different skin diseases have different compositions and structures, and their optical parameters and biological characteristics should be different, which implies that the optical clearing technique may have selectivity and may not be suitable for all kinds of skin diseases.

Hidradenitis suppurativa - Management, comorbidities and monitoring.

PubMed

Vekic, Dunja A; Cains, Geoffrey D

2017-01-01

Hidradenitis suppurativa (HS) is a chronic inflammatory disease presenting in intertriginous areas. HS is associated with a number of disease-modifying comorbidities, including metabolic syndrome and androgen dysfunction, and smoking. This review provides a synopsis of the aetiology and diagnosis of HS, and an overview of management for this often devastating disease. The clinical course and disease severity of HS are variable among patients. HS has profound physical and psychological consequences that affect patients' quality of life. Effective treatment is now a realistic goal, but needs to be combined with treatment of the comorbidities and psyche. Evidence-based management guidelines have been established for the management of this disease. General practitioners play a pivotal role in the holistic treatment of this disease.

Familial periodontal disease in the Cayo Santiago rhesus macaques.

PubMed

Gonzalez, Octavio A; Orraca, Luis; Kensler, Terry B; Gonzalez-Martinez, Janis; Maldonado, Elizabeth; Ebersole, Jeffrey L

2016-01-01

Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease. © 2016 Wiley Periodicals, Inc.

Familial Periodontal Disease in the Cayo Santiago Rhesus Macaques

PubMed Central

Gonzalez, O.A.; Orraca, L.; Kensler, T. B.; Gonzalez-Martinez, J.; Maldonado, E.; Ebersole, J.L.

2015-01-01

Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally-occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5–31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all 4 quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease. PMID:25708960

Republished review: Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Association of restless legs syndrome, pain, and mood disorders in Parkinson's disease.

PubMed

Rana, Abdul Qayyum; Qureshi, Abdul Rehman M; Rahman, Labiba; Jesudasan, Ajantha; Hafez, Kevin K; Rana, Mohammad A

2016-01-01

The objectives of the study were to analyze the association between Parkinson's disease and restless legs syndrome, and to explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson's disease patients and 123 non-Parkinson's disease patients matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination through the restless legs syndrome diagnostic criteria and the following inventories; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson's disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson's disease patients' comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson's disease only, Parkinson's disease anxiety, and Parkinson's disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson's disease patients with anxiety and depression, in comparison to Parkinson's disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.

Impetigo and scabies - Disease burden and modern treatment strategies.

PubMed

Yeoh, Daniel K; Bowen, Asha C; Carapetis, Jonathan R

2016-07-05

Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment. Copyright © 2016. Published by Elsevier Ltd.

Therapeutic Targeting of Siglecs using Antibody- and Glycan-based Approaches

PubMed Central

Angata, Takashi; Nycholat, Corwin M.; Macauley, Matthew S.

2015-01-01

The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell-type specific expression pattern, endocytic properties, high expression on certain lymphomas/leukemias, and ability to modulate receptor signaling. Siglec-targeting approaches with therapeutic potential encompass antibody- and glycan-based strategies. Several antibody-based therapies are in clinical trials and continue to be developed for the treatment of lymphoma/leukemia and autoimmune disease, while the therapeutic potential of glycan-based strategies for cargo-delivery and immunomodulation is a promising new approach. Here, we review these strategies with special emphasis on emerging approaches and disease areas that may benefit from targeting the Siglec family. PMID:26435210

Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.

PubMed

Costello, Rebecca B; Elin, Ronald J; Rosanoff, Andrea; Wallace, Taylor C; Guerrero-Romero, Fernando; Hruby, Adela; Lutsey, Pamela L; Nielsen, Forrest H; Rodriguez-Moran, Martha; Song, Yiqing; Van Horn, Linda V

2016-11-01

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health. © 2016 American Society for Nutrition.

Prevalence of chronic pancreatitis: Results of a primary care physician-based population study.

PubMed

Capurso, Gabriele; Archibugi, Livia; Pasquali, Piera; Aceti, Alessandro; Balducci, Paolo; Bianchi, Patrizia; Buono, Francesco; Camerucci, Stefano; Cantarini, Rosanna; Centofanti, Sergio; Colantonio, Patrizia; Cremaschi, Riccarda; Crescenzi, Sergio; Di Mauro, Caterina; Di Renzi, Davide; Filabozzi, Andrea; Fiorillo, Alfonso; Giancaspro, Giuseppe; Giovannetti, Paola; Lanna, Giuseppe; Medori, Claudio; Merletti, Emilio; Nunnari, Enzo; Paris, Francesca; Pavone, Marco; Piacenti, Angela; Rossi, Almerindo; Scamuffa, Maria Cristina; Spinelli, Giovanni; Taborchi, Marco; Valente, Biagio; Villanova, Antonella; Chiriatti, Alberto; Delle Fave, Gianfranco

2017-05-01

Data on chronic pancreatitis prevalence are scanty and usually limited to hospital-based studies. Investigating chronic pancreatitis prevalence in primary care. Participating primary care physicians reported the prevalence of chronic pancreatitis among their registered patients, environmental factors and disease characteristics. The data were centrally reviewed and chronic pancreatitis cases defined according to M-ANNHEIM criteria for diagnosis and severity and TIGAR-O classification for etiology. Twenty-three primary care physicians participated in the study. According to their judgment, 51 of 36.401 patients had chronic pancreatitis. After reviewing each patient data, 11 turned out to have definite, 5 probable, 19 borderline and 16 uncertain disease. Prevalence was 30.2/100.000 for definite cases and 44.0/100.000 for definite plus probable cases. Of the 16 patients with definite/probable diagnosis, 8 were male, with mean age of 55.6 (±16.7). Four patients had alcoholic etiology, 5 post-acute/recurrent pancreatitis, 6 were deemed to be idiopathic. Four had pancreatic exocrine insufficiency, 10 were receiving pancreatic enzymes, and six had pain. Most patients had initial stage and non-severe disease. This is the first study investigating the prevalence of chronic pancreatitis in primary care. Results suggest that the prevalence in this context is higher than in hospital-based studies, with specific features, possibly representing an earlier disease stage. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come12345

PubMed Central

Elin, Ronald J; Rosanoff, Andrea; Lutsey, Pamela L; Nielsen, Forrest H; Rodriguez-Moran, Martha

2016-01-01

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75–0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health. PMID:28140318

Fecal microbiota transplantation for gastrointestinal disorders.

PubMed

Malikowski, Thomas; Khanna, Sahil; Pardi, Darrell S

2017-01-01

The importance of the gut microbiome in human health is being increasingly recognized. The purpose of this review is to examine the existing literature pertaining to alterations in the gut microbiome and the utility of microbiome restoration therapies in gastrointestinal disorders. Imbalance and maladaptation of the microbiome, termed dysbiosis, has been associated with several disease states such as irritable bowel syndrome, Clostridium difficile infection, inflammatory bowel diseases, nonalcoholic fatty liver disease, and obesity among others. The possibility of restoration of normal microbiota has become an attractive concept for diseases in which the normal microbiome is perturbed. The rationale of using fecal microbiota transplantation to treat disease has been validated by its successful use in treating recurrent Clostridium difficile infection, which occurs as a result of decreased microbial diversity in the gut, most often in the setting of recent antibiotic treatment. Similar strategies may be applicable to other disorders. Alterations in the gut microbiome are associated with several disorders, and microbiome restoration based therapies such as fecal microbiota transplantation may be an adjunct to conventional treatments but more investigation is needed.

2015 Oman Heart Association guidelines for the management of hypertension : practical recommendations from the Oman Heart Association (OHA).

PubMed

El-Deeb, Mohammed H; Sulaiman, Kadhim J; Al-Riyami, Abdullah A; Mohsin, Nabil; Al-Mukhaini, Mohamed; Al-Lamki, Mohamed; Al-Busaidi, Noor; Al-Salmi, Issa; Al-Lawati, Jawad; Al-Rawahi, Najib; Al-Riyami, Mohamed B; Abdul-Rahman, Said; Al-Hinai, Said; Jaffer, Batool; Al-Wahaebi, Ahmed; Al-Khalili, Hanan; Al-Zadjali, Matllooba

2015-03-01

Hypertension (HTN) is a major independent risk factor for the development of stroke, coronary artery disease (CAD), peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD). HTN is a growing public health problem in Oman, almost certainly the most prevalent modifiable risk factor for cardiovascular disease (CVD). The risk of CVD in patients with HTN can be greatly reduced with lifestyle modifications and effective antihypertensive therapy. Randomized trials have shown that blood pressure (BP) lowering produces rapid reductions in CV risk. Several studies have shown that the majority of the hypertensive patients remain uncontrolled. It is well established that the observed poor control of the disease is not only related to poor adherence to medications, but also to limited awareness and adherence to evidence-based management of hypertension among physicians. Several guidelines for the management of patients with hypertension have been published. However, the aim of this document is to provide the busy physicians in Oman with more concise and direct approach towards implementing these guidelines into clinical practice.

A population-based cohort study defines prognoses in severe chronic kidney disease.

PubMed

Tonelli, Marcello; Wiebe, Natasha; James, Matthew T; Klarenbach, Scott W; Manns, Braden J; Ravani, Pietro; Strippoli, Giovanni F M; Hemmelgarn, Brenda R

2018-05-01

In older people with chronic kidney disease (CKD) and comorbidities, the risk of death or disability may overshadow the risk of kidney failure. To help refine this we did a retrospective population-based cohort study to evaluate the relative likelihood of adverse outcomes as functions of age and comorbidity burden among 47,228 adults with severe non-dialysis dependent CKD. We identified comorbidities using 29 validated algorithms applied to administrative data and assessed death, end-stage renal disease (ESRD), cardiovascular disease (CVD) events, and long-term care. Over five years of follow-up, 53.4% of participants died, 24.1% had a CVD event, 14.3% were placed into long-term care and 5.3% developed ESRD. Death was 145 times more likely and 11 times more likely than ESRD for participants aged 80 years or more and 60-79 years, respectively; long-term care was 30 times more likely and 1.7 times as likely as ESRD for participants aged 80 years or more and 60-79 years, respectively. Increasing comorbidity burden was similarly associated with increased risk of death and long-term care placement but reduced the likelihood of ESRD, and the risks of increasing age were similarly incremental. Thus, among patients with severe CKD, older age and/or higher comorbidity burden, death and long-term care placement are markedly more likely than ESRD. Hence, clinicians, patients and families should all consider the relative magnitude of these risks when making decisions about renal replacement. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

PubMed

Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

2016-01-01

The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

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

Agreement between Results of Home Sleep Testing for Obstructive Sleep Apnea with and without a Sleep Specialist

PubMed Central

Aurora, R. Nisha; Putcha, Nirupama; Swartz, Rachel; Punjabi, Naresh M.

2016-01-01

Background Obstructive sleep apnea is a prevalent yet underdiagnosed condition associated with cardiovascular morbidity and mortality. Home sleep testing offers an efficient means for diagnosing obstructive sleep apnea but has primarily been deployed in clinical samples with a high pretest probability. The current study sought to assess if obstructive sleep apnea can be diagnosed with home sleep testing in a non-referred sample without involvement of a sleep medicine specialist. Methods A study of community-based adults with untreated obstructive sleep apnea was undertaken. Misclassification of disease severity based on home sleep testing with and without involvement of a sleep medicine specialist was assessed, and agreement was characterized using scatter plots, Pearson's correlation coefficient, Bland-Altman analysis, and the kappa statistic. Analyses were also conducted to assess whether any observed differences varied as a function of pretest probability of obstructive sleep apnea or subjective sleepiness. Results The sample consisted of 191 subjects with over half (56.5%) having obstructive sleep apnea. Without involvement of a sleep medicine specialist, obstructive sleep apnea was not identified in only 5.8% of the sample. Analyses comparing the categorical assessment of disease severity with and without a sleep medicine specialist showed that in total, 32 subjects (16.8%) were misclassified. Agreement in the disease severity with and without a sleep medicine specialist was not influenced by the pretest probability or daytime sleep tendency. Conclusion Obstructive sleep apnea can be reliably identified with home sleep testing in a non-referred sample irrespective of the pretest probability of the disease. PMID:26968467

Achieving Symptom Control in Patients with Moderate Asthma

PubMed Central

Weir, Nargues A.; Levine, Stewart J.

2012-01-01

Disease severity in asthma can be classified as mild, moderate or severe based upon the frequency of symptoms or the severity of airflow obstruction. This review will focus on the treatment of youths greater than 12 years of age and adults with moderate persistent asthma. Moderate asthmatics may have daily symptoms that cause some limitation with normal daily activities and require use of a rescue inhaled short-acting beta2-agonist inhaler or experience nocturnal awakenings secondary to asthma that occur more than once per week. Furthermore, spirometry may reveal airflow obstruction with a reduction in FEV1 to between 60% and 80% of predicted. Although inhaled corticosteroids (ICS) are the primary controller medication used to modify symptoms in moderate asthmatics, additional controller medications, such as inhaled long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA) or theophylline, are often needed to obtain optimal disease control. While the addition of an inhaled LABA to an ICS is very effective at improving disease control in moderate asthma, concerns have arisen over the safety of LABAs, in particular the risk of asthma-related death. Therefore, consideration may be given to initially adding a LTRA, rather than a LABA, to ICS when asthma symptoms are not adequately controlled by ICS alone. Furthermore, individualization of medication regimens, treatment of co-morbid conditions, and patient education are crucial to optimizing compliance with therapy, improving disease control, and reducing the risk of exacerbations. Lastly, the development of new asthma treatments, perhaps based upon personalized medicine, may revolutionize the future treatment of moderate asthma. PMID:22259262

Small bowel video capsule endoscopy in Crohn's disease: What have we learned in the last ten years?

PubMed

Lucendo, Alfredo J; Guagnozzi, Danila

2011-02-16

Since its introduction in 2001, capsule endoscopy (CE) has become the most important advance in the study of small bowel disease, including Crohn's disease (CD). This technique has been demonstrated to be superior to all other current forms of radiological investigation in detecting mucosal abnormalities of small bowel nonstricturing CD. CE has proven to be extremely useful in diagnosing CD in patients with inconclusive findings from ileocolonoscopy and x-ray-based studies. Almost half of all patients with CD involving the ileum also present lesions in proximal intestinal segments, with the small bowel being exclusively involved in up to 30% of all CD cases. Despite the widespread use of CE, several questions concerning the utility of this technique remain unanswered. The lack of commonly agreed diagnostic criteria for defining CD lesions with the aid of CE may have had an influence on the variation in diagnostic results for CE reported in the literature. The utility of CE in monitoring CD and in guiding therapy has also been proposed. Furthermore, CE could be a useful second-line technique for patients with an established diagnosis of CD and unexplained symptoms. Finally, as no threshold for CD diagnosis has been agreed upon, a severity scale of mucosal disease activity has not been universally followed. None of the available activity indexes based on CE findings has been independently validated. This article discusses several cutting-edge aspects of the usefulness of CE in CD 10 years after its introduction as a sensible method to study the small intestine.

Small bowel video capsule endoscopy in Crohn’s disease: What have we learned in the last ten years?

PubMed Central

Lucendo, Alfredo J; Guagnozzi, Danila

2011-01-01

Since its introduction in 2001, capsule endoscopy (CE) has become the most important advance in the study of small bowel disease, including Crohn’s disease (CD). This technique has been demonstrated to be superior to all other current forms of radiological investigation in detecting mucosal abnormalities of small bowel nonstricturing CD. CE has proven to be extremely useful in diagnosing CD in patients with inconclusive findings from ileocolonoscopy and x-ray-based studies. Almost half of all patients with CD involving the ileum also present lesions in proximal intestinal segments, with the small bowel being exclusively involved in up to 30% of all CD cases. Despite the widespread use of CE, several questions concerning the utility of this technique remain unanswered. The lack of commonly agreed diagnostic criteria for defining CD lesions with the aid of CE may have had an influence on the variation in diagnostic results for CE reported in the literature. The utility of CE in monitoring CD and in guiding therapy has also been proposed. Furthermore, CE could be a useful second-line technique for patients with an established diagnosis of CD and unexplained symptoms. Finally, as no threshold for CD diagnosis has been agreed upon, a severity scale of mucosal disease activity has not been universally followed. None of the available activity indexes based on CE findings has been independently validated. This article discusses several cutting-edge aspects of the usefulness of CE in CD 10 years after its introduction as a sensible method to study the small intestine. PMID:21403813

Methodology and potential pitfalls in allergic diseases study designs: measurements for the assessment of the overall severity of atopic dermatitis--the four step severity score (FSSS), SCORAD-related, electronic system, for the simple and rapid evaluation of the skin and mucosal allergic inflammation.

PubMed

Mastrandrea, F; Pecora, S; Scatena, C; Cadario, G

2005-11-01

Medical statistics may contribute to ameliorate research by improving the design of studies and identifying the optimal method for the analysis of results. Sometimes, nevertheless, it could be misemployed flawing the benefit potential. Allergic diseases pathogenesis is recognized to be systemic but global initiatives such as GINA and ARIA documents define allergic asthma and rhinitis as organ diseases; such an asymmetrical view raises a set of known and unknown confounding that could influence the quality of the process of evidence-based decision-making (topic symptomatic therapeutic interventions versus systemic pathogenetic interventions). This article shows the first scoring system for the assessment of atopic dermatitis lesions developed in the allergy-area. A four-step severity score (FSSS) was chosen in agreement with those developed for asthma and rhinitis in global initiatives, to avoid any further differences in evaluating the severity of allergic diseases. FSSS relates each step with the objective signs of the SCORAD and rates the disease course as intermittent or persistent. A devoted electronic program has been also framed to allow a quick and simple contemporary evaluation of the SCORAD Index (Section I) and of the FSSS (Section II); the program furthermore foresees a third section named ESAS (Extra Skin Allergic Signs) (Section III) in which it is possible to check whether organs other than the skin are involved by the allergic inflammation. The limitations potential generated by a misemployment of medical statistics for clinical trials designed to establish benefits rising from specific immunotherapy for allergic diseases have been also discussed extensively.

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).

Leaf and canopy reflectance spectrometry applied to the estimation of angular leaf spot disease severity of common bean crops

PubMed Central

Martínez-Martínez, Víctor; Machado, Marley L.; Pinto, Francisco A. C.

2018-01-01

This study is aimed at (i) estimating the angular leaf spot (ALS) disease severity in common beans crops in Brazil, caused by the fungus Pseudocercospora griseola, employing leaf and canopy spectral reflectance data, (ii) evaluating the informative spectral regions in the detection, and (iii) comparing the estimation accuracy when the reflectance or the first derivative reflectance (FDR) is employed. Three data sets of useful spectral reflectance measurements in the 440 to 850 nm range were employed; measurements were taken over the leaves and canopy of bean crops with different levels of disease. A system based in Principal Component Analysis (PCA) and Artificial Neural Networks (ANN) was developed to estimate the disease severity from leaf and canopy hyperspectral reflectance spectra. Levels of disease to be taken as true reference were determined from the proportion of the total leaf surface covered by necrotic lesions on RGB images. When estimating ALS disease severity in bean crops by using hyperspectral reflectance spectrometry, this study suggests that (i) successful estimations with coefficients of determination up to 0.87 can be achieved if the spectra is acquired by the spectroradiometer in contact with the leaves, (ii) unsuccessful estimations are obtained when the spectra are acquired by the spectroradiometer from one or more meters above the crop, (iii) the red to near-infrared spectral region (630–850 nm) offers the same precision in the estimation as the blue to near-infrared spectral region (440–850), and (iv) neither significant improvements nor significant detriments are achieved when the input data to the estimation processing system are the FDR spectra, instead of the reflectance spectra. PMID:29698420

Costs of providing infusion therapy for patients with inflammatory bowel disease in a hospital-based infusion center setting.

PubMed

Afzali, Anita; Ogden, Kristine; Friedman, Michael L; Chao, Jingdong; Wang, Anthony

2017-04-01

Inflammatory bowel disease (IBD) (e.g. ulcerative colitis [UC] and Crohn's disease [CD]) severely impacts patient quality-of-life. Moderate-to-severe disease is often treated with biologics requiring infusion therapy, adding incremental costs beyond drug costs. This study evaluates US hospital-based infusion services costs for treatment of UC or CD patients receiving infliximab or vedolizumab therapy. A model was developed, estimating annual costs of providing monitored infusions using an activity-based costing framework approach. Multiple sources (published literature, treatment product inserts) informed base-case model input estimates. The total modeled per patient infusion therapy costs in Year 1 with infliximab and vedolizumab was $38,782 and $41,320, respectively, and Year 2+, $49,897 and $36,197, respectively. Drug acquisition cost was the largest total costs driver (90-93%), followed by costs associated with hospital-based infusion provision: labor (53-56%, non-drug costs), allocated overhead (23%, non-drug costs), non-labor (23%, non-drug costs), and laboratory (7-10%, non-drug costs). Limitations included reliance on published estimates, base-case cost estimates infusion drug, and supplies, not accounting for volume pricing, assumption of a small hospital infusion center, and that, given the model adopts the hospital perspective, costs to the patient were not included in infusion administration cost base-case estimates. This model is an early step towards a framework to fully analyze infusion therapies' associated costs. Given the lack of published data, it would be beneficial for hospital administrators to assess total costs and trade-offs with alternative means of providing biologic therapies. This analysis highlights the value to hospital administrators of assessing cost associated with infusion patient mix to make more informed resource allocation decisions. As the landscape for reimbursement changes, tools for evaluating the costs of infusion therapy may help hospital administrators make informed choices and weigh trade-offs associated with providing infusion services for IBD patients.

[Medical treatment of juvenile idiopathic arthritis].

PubMed

Horneff, Gerd; Augustin, Sankt

2008-09-01

Juvenile idiopathic arthritis is the most common chronic autoimmune disease. The outcome of this inflammatory disease is uncertain. Patients may suffer from severe joint damage leading to mutilations as well as from extraarticular manifestations. The prognosis is variable and depends in part on the number of affected joints and the occurrence of extraarticular manifestations. Pharmacomedical treatment has changed markedly in the last decade. It consists of a combination therapy including nonsteroidal antirheumatics, glucocorticoids either systemic or intraarticular, classical disease modifying drugs like sulfasalazine and methotrexate as well as leflunomide and biologicals. These new therapeutic strategies have effected dramatic improvements also in patients with severe, so far intractable disease. The TNF inhibitors etanercept and adalimumab have succeeded in double blind controlled trials, while infliximab failed to show significant superiority over placebo. Further treatment options include inhibitors of interleukin 1 (anakinra and rilonacept), interleukin 6 (tocilizumab) and inhibitors of T-cell activation (abatacept). This review will summarize the pharmacotherapeutic options based on studies published in the literature.

Predictors of Severe Disease in Melioidosis Patients in Kuala Lumpur, Malaysia

PubMed Central

Mohd Roslani, Ardita Dewi Roslani; Tay, Sun Tee; Puthucheary, Savithri D.; Rukumani, Devi V.; Sam, I-Ching

2014-01-01

The predictors of severe disease or death were determined for 85 melioidosis patients in Kuala Lumpur, Malaysia. Most of the patients were male, > 40 years old, and diabetic. Severe disease or death occurred in 28 (32.9%) cases. Lower lymphocyte counts and positive blood cultures were significant independent predictors of severe disease, but age, presentations with pneumonia, inappropriate empirical antibiotics, or flagellin types of the infecting isolates were not. Knowledge of local predictors of severe disease is useful for clinical management. PMID:25246695

The skin in psoriasis: assessment and challenges.

PubMed

Oji, Vinzenz; Luger, Thomas A

2015-01-01

The coexistence of psoriasis arthritis (PsA) and psoriasis vulgaris in about 20% of patients with psoriasis leads to a need for rheumatologic-dermatologic team work. We summarise the role of dermatologists in assessment of the skin in psoriasis. Chronic plaque psoriasis must be differentiated from other subtypes such as generalised pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). Therapeutic management is based on the evaluation of the disease severity. Quantitative scoring of skin severity includes calculation of the Psoriasis Area and Severity Index (PASI), body surface area (BSA) as well as the Dermatology Life Quality Index (DLQI). These scoring systems do not replace the traditional dermatologic medical history and physical examination of the patient. The skin should be examined for additional skin diseases; moreover, patients should be monitored for comorbidity, most importantly PsA and cardiovascular comorbidity.

Utilisation of Healthcare and Associated Services in Huntington’s disease: a data mining study

PubMed Central

Busse, Monica; Al-Madfai, Dr. Hasan; Kenkre, Joyce; Landwehrmeyer, G. Bernhard; Bentivoglio, AnnaRita; Rosser, Anne

2011-01-01

Background: People with Huntington’s disease (HD) often require tailored healthcare and support packages that develop as the disease progresses. The Client Service Receipt Inventory (CSRI) gathers retrospective information on service utilization. This study investigated the use of formal services and informal care as measured by the CSRI and explored associations between informal care, disease severity and functional ability as measured by the Unified Huntington’s Disease Rating Scale Total Motor Score (UHDRS-TMS) and functional scales. Methods: All monitored longitudinal data from annual clinical assessments of UHDRS-TMS and functional assessments and CSRI collected under the auspices of the European Huntington’s Disease Network (EHDN) REGISTRY study between the years 2004 and 2009 were utilised in the analyses. Disease severity was reflected by UHDRS-TMS. Functional ability was measured using the UHDRS functional scales. CSRI data were analysed according to percentage use of individual formal services and total estimated hours per week of informal care. Regression analyses were conducted to identify any associations between disease severity, functional ability and hours of informal care. Results: 451 HD patients (212 female; 239 male) completed one visit; 105 patients (54 females; 51 males) completed two visits and 47 patients (20 females; 27 males) completed three visits in total over the 5 year period. The mean time between visits was 1.2 years. At visit one, 74% of the participants reported being in receipt of at least one formal hospital-based service in the previous six months, and 89% reported receipt of formal primary and community care services. In contrast, at the third visit, 62% of people had used hospital based services and 94% formal community based services in the previous six months. Fifty % of individuals required some form of informal care in the home at visit 1; this increased to 68% at visits 2 and 3. The mean (SD) estimated weekly total informal care hours at visits 1, 2 and 3 were 32.8 (49.4); 21.6 (53.6) and 21.3 (62.4) respectively. Only the scores on the Functional Assessment Scale (FAS) accounted for the variance in the weekly total informal care hours at each visit. Conclusions: Although it must be acknowledged that service use is supply driven, most HD patients across Europe surveyed as part of this study were in receipt of formal primary and community care services and to a lesser extent formal hospital based services. There was however a large reliance on informal care in the home. The FAS appear to have predictive value on informal care requirements and may have utility in facilitating pro-active service provision and in particular when managing carer burden in this population. PMID:21304753

Susceptibility based upon Chemical Interaction with Disease ...

EPA Pesticide Factsheets

One of the challenges facing toxicology and risk assessment is that numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest is the potential for chemicals to interact with background aging and disease processes, an interaction that may yield cumulative damage, altered chemical potency, and increased disease incidence. This review outlines the interactions possible between chemicals and background disease and identifies the type of information needed to evaluate such interactions. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which allows the identification of vulnerable individuals based upon the level of risk biomarker. The impact of toxic chemicals on this biomarker can then be used to predict how the chemical modifies disease risk as long as related mechanistic and toxicological data are consistent with toxicant effect on the disease process. Several case studies are briefly presented which describe the toxic chemical, the clinical biomarker and the impacted disease including: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration rate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; trichloroethylene/increased anti-nuclear antibody/autoimmunity; dioxin/increased CYP1A1/hypertension. These case studies point o

Correlation between severity of ultrasonographic nonalcoholic fatty liver disease and cardiometabolic risk among Filipino wellness patients

PubMed Central

Cuenza, Lucky R.; Razon, Tamara Louise J.; Dayrit, Juan Carlo

2017-01-01

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition which is known to be related to factors that predispose to the development of coronary artery disease as well as development of metabolic syndrome. The study aimed to determine the association between ultrasound-based grading of hepatic steatosis with metabolic profile and estimated cardiovascular risk using the Framingham Risk Score (FRS). Methods: This was a cross-sectional study on 100 Filipino patients without established cardiovascular disease who underwent a general wellness health evaluation. Cases with NAFLD diagnosed on the basis of ultrasound grading were analyzed. Comparison of demographics and metabolic parameters between grades of hepatic steatosis was performed using Kruskal Wallis test. FRS was used to assess cardiovascular risk with Spearman rank test for correlation with the degree of NAFLD. Results: Mean age was 47 ± 9.6 years, with 70% males. Mean body mass index (BMI) was 28.7 ± 5.1. Most patients had grade I NAFLD (53%), 34% were grade II, and 13% were grade III. BMI (P =0.034), liver enzymes (alanine aminotransferase [ALT], P = 0.001; aspartate aminotransferase [AST], P = 0.00), triglycerides (P = 0.047), and fasting blood sugar [FBS] (P = 0.049) were associated with fatty liver grade. No association was noted with total cholesterol (P = 0.569), high density lipoprotein (HDL) (P = 0.220), and low density lipoprotein (LDL) (P = 0.792). Using the FRS 43% were stratified as low (<10% risk), 45% as intermediate (10%-20% risk) and 12% as high risk (>20% risk). Severity of fatty liver was directly correlated with the FRS (Spearman rank 0.741, P = 0.009). Conclusion: Ultrasound-based grading of the severity of NAFLD is associated with abnormalities in the metabolic profile of patients. The FRS is correlated with increasing severity of NAFLD based on ultrasound. These findings suggest that the presence of NAFLD may be a marker for the presence of increased cardiovascular risk and may help identify patients who may benefit from more aggressive therapies to prevent development of adverse cardiovascular events. PMID:28740627

Predictors of performance-based measures of instrumental activities of daily living in nondemented patients with Parkinson's disease.

PubMed

Pirogovsky, Eva; Martinez-Hannon, Mercedes; Schiehser, Dawn M; Lessig, Stephanie L; Song, David D; Litvan, Irene; Filoteo, J Vincent

2013-01-01

Few studies have examined instrumental activities of daily living (iADLs) in nondemented Parkinson's disease (PD), and the majority of these studies have used report-based measures, which can have limited validity. The present study had two main goals: (a) to examine the performance of nondemented PD patients on two performance-based measures of iADLs, which are considered more objective functional measures, and (b) to examine the cognitive, motor, and psychiatric correlates of iADL impairment in PD. Ninety-eight nondemented PD patients and 47 healthy older adults were administered performance-based measures that assess the ability to manage medications (Medication Management Ability Assessment) and finances (University of California, San Diego, UCSD, Performance-based Skills Assessment), the Mattis Dementia Rating Scale to assess global cognitive functioning, the Unified Parkinson's Disease Rating Scale Part III to assess motor symptom severity, and the Geriatric Depression Scale to assess depressive symptoms. Nondemented PD patients demonstrated significantly impaired scores relative to the healthy comparison group on the performance-based measure of financial management, but there were no significant group differences in medication management. Global cognitive functioning, motor severity, and depressive symptoms did not correlate with scores on either of the functional measures, except for a small correlation between depressive symptoms and financial management. The two performance-based measures of iADL functioning did not correlate with one another. These findings suggest that medication and financial management may not be predicted based on global cognitive functioning and that iADLs may not be represented by a single construct. Furthermore, these findings suggest the potential need for a multidimensional approach to assessing iADLs.

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

A mathematical model of Chagas disease transmission

NASA Astrophysics Data System (ADS)

Hidayat, Dayat; Nugraha, Edwin Setiawan; Nuraini, Nuning

2018-03-01

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi which is transmitted to human by insects of the subfamily Triatominae, including Rhodnius prolixus. This disease is a major problem in several countries of Latin America. A mathematical model of Chagas disease with separate vector reservoir and a neighboring human resident is constructed. The basic reproductive ratio is obtained and stability analysis of the equilibria is shown. We also performed sensitivity populations dynamics of infected humans and infected insects based on migration rate, carrying capacity, and infection rate parameters. Our findings showed that the dynamics of the infected human and insect is mostly affected by carrying capacity insect in the settlement.

Celiac disease biodetection using lossy-mode resonances generated in tapered single-mode optical fibers

NASA Astrophysics Data System (ADS)

Socorro, A. B.; Corres, J. M.; Del Villar, I.; Matias, I. R.; Arregui, F. J.

2014-05-01

This work presents the development and test of an anti-gliadin antibodies biosensor based on lossy mode resonances (LMRs) to detect celiac disease. Several polyelectrolites were used to perform layer-by-layer assembly processes in order to generate the LMR and to fabricate a gliadin-embedded thin-film. The LMR shifted 20 nm when immersed in a 5 ppm anti-gliadin antibodies-PBS solution, what makes this bioprobe suitable for detecting celiac disease. This is the first time, to our knowledge, that LMRs are used to detect celiac disease and these results suppose promising prospects on the use of such phenomena as biological detectors.

The fossil tabanids (Diptera Tabanidae): when they began to appreciate warm blood and when they began transmit diseases?

PubMed

Martins-Neto, Rafael Gioia

2003-01-01

A discussion of the known fossil tabanids (Diptera Tabanidae) is presented based on fossil evidence. This includes the origin of the hemathophagy in the Brachycera, more specifically for tabanids. Several tabanid species in the extant fauna are vectors for disease-producing organisms that affect humans and animals. Bacteria, viruses, rickettsiae, protozoa, and filarial worms can be transmitted by them, causing such diseases as anthrax, tularemia, anaplasmosis, various forms of trypanosomiasis, Q fever, and filariasis. However, if tabanids are directly responsible for all of these diseases is not consensual and the known fossil evidence is presented here.

Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal Disease virus in chicken embryo fibroblasts in vitro.

PubMed

Ganguly, Bhaskar; Umapathi, Vijaypillai; Rastogi, Sunil Kumar

2018-01-01

Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera , inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.

Multimodal Neuroimaging: Basic Concepts and Classification of Neuropsychiatric Diseases.

PubMed

Tulay, Emine Elif; Metin, Barış; Tarhan, Nevzat; Arıkan, Mehmet Kemal

2018-06-01

Neuroimaging techniques are widely used in neuroscience to visualize neural activity, to improve our understanding of brain mechanisms, and to identify biomarkers-especially for psychiatric diseases; however, each neuroimaging technique has several limitations. These limitations led to the development of multimodal neuroimaging (MN), which combines data obtained from multiple neuroimaging techniques, such as electroencephalography, functional magnetic resonance imaging, and yields more detailed information about brain dynamics. There are several types of MN, including visual inspection, data integration, and data fusion. This literature review aimed to provide a brief summary and basic information about MN techniques (data fusion approaches in particular) and classification approaches. Data fusion approaches are generally categorized as asymmetric and symmetric. The present review focused exclusively on studies based on symmetric data fusion methods (data-driven methods), such as independent component analysis and principal component analysis. Machine learning techniques have recently been introduced for use in identifying diseases and biomarkers of disease. The machine learning technique most widely used by neuroscientists is classification-especially support vector machine classification. Several studies differentiated patients with psychiatric diseases and healthy controls with using combined datasets. The common conclusion among these studies is that the prediction of diseases increases when combining data via MN techniques; however, there remain a few challenges associated with MN, such as sample size. Perhaps in the future N-way fusion can be used to combine multiple neuroimaging techniques or nonimaging predictors (eg, cognitive ability) to overcome the limitations of MN.

Natural history of aortic valve disease following intervention for rheumatic mitral valve disease.

PubMed

Namboodiri, Narayanan; Remash, Krishnan; Tharakan, Jaganmohan A; Shajeem, Othayoth; Nair, Krishnakumar; Titus, Thomas; Ajitkumar, Valaparambil K; Sivasankaran, Sivasubramonian; Krishnamoorthy, Kavassery M; Harikrishnan, Sivadasan P; Harikrishnan, Madhavankutty S; Bijulal, Sasidharan

2009-01-01

A significant proportion of patients who require interventions for rheumatic mitral valve (MV) disease have coexisting aortic valve (AV) disease. To date, little is known of the natural history of AV disease in these patients. The details of a cohort of 200 patients (146 females, 54 males; mean age at MV intervention 30.3 +/- 9.9 years) with rheumatic heart disease were retrospectively reviewed. The patients had undergone an index MV intervention (either closed or balloon mitral valvotomy) or MV replacement between 1994 and 1996, and received long-term regular follow up examinations. The clinical and echocardiographic data at entry and at follow up were noted. Patients were allocated to two groups, based on whether the AV disease was absent (group I, n=98) or present (group II, n=102) at baseline. The AV disease was categorized as thickening only (group IIA), isolated aortic regurgitation (AR) (group IIB), or combined aortic stenosis (AS) and AR (group IIC). No patient had isolated AS at baseline. The mean follow up period was 9.3 +/- 1.07 years; during which 10 patients in group I developed new AV disease, which included AV thickening only (n=2), trivial-mild AR (n=7) and mild AS with trivial AR (n=1). Of 16 patients in group IIA, 11 developed isolated AR, and one patient progressed to have mild AS and AR. Among 69 patients in group IIB, 22 (31.9%) developed AS, and all had either mild (n=8) or moderate (n=14) AR with mild AS. Group IIC included 17 patients with mild combined AV disease at baseline, except for moderate AS and moderate AR in one patient each. Among 16 patients with mild AS in group IIC, six progressed to moderate AS and two to severe AS. AR became moderate in 10 patients and severe in one patient. The two patients who progressed to severe AS requiring AV replacement had mild AS at baseline. No patient who developed new combined AV disease had lesions with severity more than mild AS or moderate AR. On logistic regression analysis of the variables predisposing to progression of AV disease, such as age, gender, history of rheumatic fever (RF) and recurrence, and interval from RF episode to symptom onset, only the initial AV gradient was identified as being statistically significant (beta coefficient 0.528, SE = 0.17, p < 0.0001). Patients with no or mild AV disease at the time of MV intervention rarely develop severe AV disease, and seldom require AV surgery over the long-term follow up. The presence of mild AS at baseline is predictive in the minority of cases where AV disease will progress relatively more rapidly.

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.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

PubMed

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-03-28

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

PubMed Central

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-01-01

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency. PMID:28350321

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders.

PubMed

Goldstein, David S; Kopin, Irwin J; Sharabi, Yehonatan

2014-12-01

Several neurodegenerative diseases involve loss of catecholamine neurons-Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of "autotoxicity"-inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the "catecholaldehyde hypothesis" for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. Published by Elsevier Inc.

Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders☆

PubMed Central

Goldstein, David S.; Kopin, Irwin J.; Sharabi, Yehonatan

2015-01-01

Several neurodegenerative diseases involve loss of catecholamine neurons—Parkinson disease is a prototypical example. Catecholamine neurons are rare in the nervous system, and why they are vulnerable in PD and related disorders has been mysterious. Accumulating evidence supports the concept of “autotoxicity”—inherent cytotoxicity of catecholamines and their metabolites in the cells in which they are produced. According to the “catecholaldehyde hypothesis” for the pathogenesis of Parkinson disease, long-term increased build-up of 3,4-dihydroxyphenylacetaldehyde (DOPAL), the catecholaldehyde metabolite of dopamine, causes or contributes to the eventual death of dopaminergic neurons. Lewy bodies, a neuropathologic hallmark of PD, contain precipitated alpha-synuclein. Bases for the tendency of alpha-synuclein to precipitate in the cytoplasm of catecholaminergic neurons have also been mysterious. Since DOPAL potently oligomerizes and aggregates alpha-synuclein, the catecholaldehyde hypothesis provides a link between alpha-synucleinopathy and catecholamine neuron loss in Lewy body diseases. The concept developed here is that DOPAL and alpha-synuclein are nodes in a complex nexus of interacting homeostatic systems. Dysfunctions of several processes, including decreased vesicular sequestration of cytoplasmic catecholamines, decreased aldehyde dehydrogenase activity, and oligomerization of alpha-synuclein, lead to conversion from the stability afforded by negative feedback regulation to the instability, degeneration, and system failure caused by induction of positive feedback loops. These dysfunctions result from diverse combinations of genetic predispositions, environmental exposures, stress, and time. The notion of catecholamine autotoxicity has several implications for treatment, disease modification, and prevention. Conversely, disease modification clinical trials would provide key tests of the catecholaldehyde hypothesis. PMID:24945828

The study of the oipA and dupA genes in Helicobacter pylori strains and their relationship with different gastroduodenal diseases

PubMed Central

Souod, Negar; Sarshar, Meysam; Dabiri, Hossein; Momtaz, Hassan; Kargar, Mohammad; Mohammadzadeh, Alireza; Abdi, Saeed

2015-01-01

Aim: The purpose of this investigation was to determine the oipA and dupA genes of Helicobacter pylori isolates from west of Iran; Chaharmahalo Bakhtiyari region and find their relationship with the severity of the gastroduodenal diseases. Background: Helicobacter pylori is an organism responsible for many gastroduodenal diseases. Many studies suggest that genetic diversity in H. pylori virulence factors such as oipA and dupA genes is high among isolates of different geographic regions and may cause more severe diseases. Patients and methods: In this cross-sectional study, gastric biopsy specimens were taken from 150 patients suffering from gastroduodenal diseases. The presence of ureC, dupA and oipA genes was tested by polymerase chain reaction (PCR). Results: Overall, 123 (82%) H. pylori strains were isolated from 150 specimens. dupA gene was detected in 41 (33.33%) H.pylori-positive specimens. There was a reverse correlation between this gene and gastric cancer. The oipA gene was found in 88 (71.54%) samples and statistically there was no association between this gene and gastric disorders. As statistical analyses revealed, the presence of the dupA was more common in isolates with the oipA negative. Conclusion: Based on our findings, the presence of dupA gene can be considered as a marker for the onset of severe diseases. However, the oipA gene cannot be regarded for prediction of gastroenterology diseases. Meanwhile, extended molecular epidemiology researches in other populations are recommended. PMID:26171137

A rolling phenotype in Crohn's disease.

PubMed

Irwin, James; Ferguson, Emma; Simms, Lisa A; Hanigan, Katherine; Carbonnel, Franck; Radford-Smith, Graham

2017-01-01

The Montreal classification of disease behaviour in Crohn's disease describes progression of disease towards a stricturing and penetrating phenotype. In the present paper, we propose an alternative representation of the long-term course of Crohn's disease complications, the rolling phenotype. As is commonly observed in clinical practice, this definition allows progression to a more severe phenotype (stricturing, penetrating) but also, regression to a less severe behaviour (inflammatory, or remission) over time. All patients diagnosed with Crohn's Disease between 01/01/1994 and 01/03/2008, managed at a single centre and observed for a minimum of 5 years, had development and resolution of all complications recorded. A rolling phenotype was defined at each time point based on all observed complications in the three years prior to the time point. Phenotype was defined as B1, B2, B3, or B23 (penetrating and stenotic). The progression over time of the rolling phenotype was compared to that of the cumulative Montreal phenotype. 305 patients were observed a median of 10.0 (Intraquartile range 7.3-13.7) years. Longitudinal progression of rolling phenotype demonstrated a consistent proportion of patients with B1 (70%), B2 (20%), B3 (5%) and B23 (5%) phenotypes. These proportions were observed regardless of initial phenotype. In contrast, the cumulative Montreal phenotype progressed towards a more severe phenotype with time (B1 (39%), B2 (26%), B3(35%) at 10 years). A rolling phenotype provides an alternative view of the longitudinal burden of intra-abdominal complications in Crohn's disease. From this viewpoint, 70% of patients have durable freedom from complication over time (>3 years).

Disease Severity and Domain Specific Arthritis Self-Efficacy: Relationships to Pain and Functioning in Rheumatoid Arthritis Patients

PubMed Central

Somers, Tamara J.; Shelby, Rebecca A.; Keefe, Francis J.; Godiwala, Neha; Lumley, Mark A.; Mosley-Williams, Angelia; Rice, John R.; Caldwell, David

2010-01-01

Objective Examining the degree to which disease severity and domains of self-efficacy (pain, function, other symptoms) explain pain and functioning in rheumatoid arthritis patients. Methods Patients (N=263) completed the Arthritis Impact Measurements Scales-2 to assess pain and functioning (physical, affective, and social), the Arthritis Self-Efficacy Scale to assess three self-efficacy domains (pain, physical function, other); disease severity was assessed with C-reactive protein, physician's rating, abnormal joint count. Structural equation modeling was used to examine hypotheses: 1) does disease severity have a direct relationship with pain and each area of functioning, 2) does disease severity have a direct relationship with each arthritis self-efficacy domain, and 3) do the self-efficacy domains mediate the relationship between disease severity and RA pain and each area of functioning. Results Disease severity was related to pain, physical functioning, and each self-efficacy domain (β's=.28-.56; p's<.001). Each self-efficacy domain was related to its respective domain of functioning (e.g., self-efficacy for pain was related to pain) (β's=.36-.54; p's<.001). Self-efficacy mediated the relationship between disease severity and pain and functioning (β's=.12-.19; p's<.001). Self-efficacy for pain control and to perform functional tasks accounted for 32-42% of disease severity's total effect on their respective outcomes (e.g., self-efficacy for pain control accounted for 32% of disease severity's total effect on pain). Variance accounted for by the total model was 52% for pain, 53% for physical functioning, and 44% for affective and social functioning. Conclusions Disease severity and self-efficacy both impact RA functioning and intervening in these areas may lead to better outcomes. PMID:20535796

Understanding the direction of the relationship between white matter hyperintensities of vascular origin, sleep quality, and chronic kidney disease-Results from the Atahualpa Project.

PubMed

Del Brutto, Oscar H; Mera, Robertino M

2018-02-01

The burden of cerebral small vessel disease, sleep disorders, and chronic kidney disease is on the rise in remote rural settings. However, information on potential links between these conditions is limited. We aimed to assess the relationships between these conditions in community-dwelling older adults living in rural Ecuador. Atahualpa residents aged ≥60 years were offered a brain MRI. A venous blood sample was obtained for serum creatinine determination. Baseline interviews and procedures were directed to assess demographics, cardiovascular risk factors, and sleep quality. Using generalized structural equation modeling (GSEM), we assessed the associations between white matter hyperintensities (WMH) of vascular origin, sleep quality and kidney function, as well as the directions of the relationships between these variables. Of 423 candidates, 314 (74%) were enrolled. Moderate-to-severe WMH were noticed in 74 (24%) individuals, poor sleep quality in 101 (31%), and moderate-to-severe chronic kidney disease in 28 (9%). GSEM showed that the direction of the effect was from kidney function to WMH and from the latter to sleep quality. Of independent variables investigated, worse kidney function was associated with age, high glucose levels and male sex. WMH was associated with cholesterol blood levels, blood pressure, level of education and severe edentulism. Poor sleep quality was associated with poor physical activity. This population based study shows that chronic kidney disease is associated with increased severity of WMH, which, in turn, is associated with a poor sleep quality. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Parkinson's disease candidate gene prioritization based on expression profile of midbrain dopaminergic neurons

PubMed Central

2010-01-01

Background Parkinson's disease is the second most common neurodegenerative disorder. The pathological hallmark of the disease is degeneration of midbrain dopaminergic neurons. Genetic association studies have linked 13 human chromosomal loci to Parkinson's disease. Identification of gene(s), as part of the etiology of Parkinson's disease, within the large number of genes residing in these loci can be achieved through several approaches, including screening methods, and considering appropriate criteria. Since several of the indentified Parkinson's disease genes are expressed in substantia nigra pars compact of the midbrain, expression within the neurons of this area could be a suitable criterion to limit the number of candidates and identify PD genes. Methods In this work we have used the combination of findings from six rodent transcriptome analysis studies on the gene expression profile of midbrain dopaminergic neurons and the PARK loci in OMIM (Online Mendelian Inheritance in Man) database, to identify new candidate genes for Parkinson's disease. Results Merging the two datasets, we identified 20 genes within PARK loci, 7 of which are located in an orphan Parkinson's disease locus and one, which had been identified as a disease gene. In addition to identifying a set of candidates for further genetic association studies, these results show that the criteria of expression in midbrain dopaminergic neurons may be used to narrow down the number of genes in PARK loci for such studies. PMID:20716345

Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture'…?

PubMed

Thomson, P J; Goodson, M L; Smith, D R

2017-11-01

Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A critical analysis of disease-associated DNA polymorphisms in the genes of cattle, goat, sheep, and pig

PubMed Central

Ibeagha-Awemu, Eveline M.; Kgwatalala, Patrick; Ibeagha, Aloysius E.

2008-01-01

Genetic variations through their effects on gene expression and protein function underlie disease susceptibility in farm animal species. The variations are in the form of single nucleotide polymorphisms, deletions/insertions of nucleotides or whole genes, gene or whole chromosomal rearrangements, gene duplications, and copy number polymorphisms or variants. They exert varying degrees of effects on gene action, such as substitution of an amino acid for another, shift in reading frame and premature termination of translation, and complete deletion of entire exon(s) or gene(s) in diseased individuals. These factors influence gene function by affecting mRNA splicing pattern or by altering/eliminating protein function. Elucidating the genetic bases of diseases under the control of many genes is very challenging, and it is compounded by several factors, including host × pathogen × environment interactions. In this review, the genetic variations that underlie several diseases of livestock (under monogenic and polygenic control) are analyzed. Also, factors hampering research efforts toward identification of genetic influences on animal disease identification and control are highlighted. A better understanding of the factors analyzed could be better harnessed to effectively identify and control, genetically, livestock diseases. Finally, genetic control of animal diseases can reduce the costs associated with diseases, improve animal welfare, and provide healthy animal products to consumers, and should be given more attention. PMID:18350334

Variations in diet cause alterations in microbiota and metabolites that follow changes in disease severity in a multiple sclerosis model.

PubMed

Libbey, J E; Sanchez, J M; Doty, D J; Sim, J T; Cusick, M F; Cox, J E; Fischer, K F; Round, J L; Fujinami, R S

2018-04-25

Multiple sclerosis (MS) is a metabolically demanding disease involving immune-mediated destruction of myelin in the central nervous system. We previously demonstrated a significant alteration in disease course in the experimental autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on the established crosstalk between metabolism and gut microbiota, we took an unbiased sampling of microbiota, in the stool, and metabolites, in the serum and stool, from mice (Mus musculus) on the two different diets, the Teklad global soy protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was found to be inversely correlated with EAE severity. Therapeutic treatment with Lactobacillus paracasei resulted in a significant reduction in the incidence of disease, clinical scores and the amount of weight loss in EAE mice. Within the metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle that may explain the differences in disease severity between the different diets in EAE. This work begins to elucidate the relationship between diet, microbiota and metabolism in the EAE preclinical model of MS and identifies targets for further study with the goal to more specifically probe the complex metabolic interaction at play in EAE that may have translational relevance to MS patients.

Hidradenitis Suppurativa: A Guide for the Practicing Physician.

PubMed

Woodruff, Carina M; Charlie, Abbas M; Leslie, Kieron S

2015-12-01

Hidradenitis suppurativa is a chronic inflammatory disease of apocrine gland-bearing skin. Although immunologic derangements, genetic predisposition, obesity, and smoking are likely important factors, the pathogenesis of the disease and the effect of available treatments on disease course have not been fully elucidated. In the absence of proper treatment, chronic inflammation results in diffuse scarring and a wide array of complications, including the development of cutaneous squamous cell carcinoma. This severe and chronic disease can have detrimental effects on self-esteem and quality of life. No ideal treatment regimen has been defined, but several therapies have been found to reduce lesion severity and improve symptoms. We reviewed the literature through July 2014 for existing treatments. Published articles were obtained via systematic review of medical databases (PubMed, Embase, Google Scholar) and scrutiny of citation lists using the search terms "hidradenitis suppurativa" and "acne inversa". Given the scarce literature on treatment strategies, we also reviewed data from any case reports or prospective and retrospective studies that were located. On the basis of the existing literature, we provide an evidence-based algorithm for the management of this disease in the primary care setting. More research is needed to evaluate the comparative effectiveness of topical and systemic treatments and to better understand the pathogenesis, natural history, and subtypes of hidradenitis suppurativa. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

An algorithmic approach for the treatment of severe uncontrolled asthma

PubMed Central

Zervas, Eleftherios; Samitas, Konstantinos; Papaioannou, Andriana I.; Bakakos, Petros; Loukides, Stelios; Gaga, Mina

2018-01-01

A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute <5% of all asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers. The diagnosis and management of severe asthma requires specialised experience, time and effort to comprehend the needs and expectations of each individual patient and incorporate those as well as his/her specific phenotype characteristics into the management planning. Although some new treatment options are currently available for these patients, there is still a need for further research into severe asthma and yet more treatment options. PMID:29531957

Induced Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Neurodegenerative Diseases.

PubMed

Cao, Lei; Tan, Lan; Jiang, Teng; Zhu, Xi-Chen; Yu, Jin-Tai

2015-08-01

Although most neurodegenerative diseases have been closely related to aberrant accumulation of aggregation-prone proteins in neurons, understanding their pathogenesis remains incomplete, and there is no treatment to delay the onset or slow the progression of many neurodegenerative diseases. The availability of induced pluripotent stem cells (iPSCs) in recapitulating the phenotypes of several late-onset neurodegenerative diseases marks the new era in in vitro modeling. The iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in these diseases and provides a novel human stem cell platform for screening new candidate therapeutics. Modeling human diseases using iPSCs has created novel opportunities for both mechanistic studies as well as for the discovery of new disease therapies. In this review, we introduce iPSC-based disease modeling in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. In addition, we discuss the implementation of iPSCs in drug discovery associated with some new techniques.

Urinary Proteomic Biomarkers for Diagnosis and Risk Stratification of Autosomal Dominant Polycystic Kidney Disease: A Multicentric Study

PubMed Central

Kistler, Andreas D.; Serra, Andreas L.; Siwy, Justyna; Poster, Diane; Krauer, Fabienne; Torres, Vicente E.; Mrug, Michal; Grantham, Jared J.; Bae, Kyongtae T.; Bost, James E.; Mullen, William; Wüthrich, Rudolf P.; Mischak, Harald; Chapman, Arlene B.

2013-01-01

Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI). The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV) based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001) with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD. PMID:23326375

Increasing Incidence and Severity of Coccidioidomycosis at a Naval Air Station

PubMed Central

Lee, Rachel U; Crum-Cianflone, Nancy F

2009-01-01

Background Increasing rates of coccidioidomycosis among the general population are being described. Given the large number of military personnel stationed and training in endemic areas, data regarding infection trends among military members would be informative. Methods We performed a retrospective epidemiologic study concerning the incidence and severity of clinical cases of coccidioidomycosis at a Naval base located in an endemic area in California. Results Eighty-two military beneficiaries at the base were diagnosed with coccidioidomycosis from January 2002 to December 2006. Among active duty personnel, the rate of coccidioidomycosis rose 10-fold during the five-year study period: 29.88 to 313.71 cases per 100,000 person-years. The incidence of coccidioidal infections occurring in active duty members was higher than other military beneficiaries at the base. The median age of patients with a coccidioidal infection was 28 years, and 73% were male. Sixty-six had primary pulmonary disease, and 14 had disseminated disease; data were unavailable for two cases. The number of disseminated cases increased significantly over time; by 2006, 30% of the diagnosed cases were disseminated disease. Among cases of dissemination, 43% occurred among white/non-Hispanics. Disseminated disease was associated with high complement fixation titers and a more recent year of diagnosis. Although the sample size was small, we found no differences in rates of disseminated disease by race, likely due to the large number of cases among Caucasians. Conclusions Coccidioidomycosis incidence rates have significantly increased during the last five years among military beneficiaries. Active duty members were more likely to develop coccidioidomycosis than dependents or retirees, perhaps related to the number and intensity of exposures in this group. PMID:18751595

A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

PubMed

Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

2014-09-24

Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes.

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

PubMed

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.